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Re this may be a strange question.

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  1. If I were you I would do the easiest thing first. Only eat tiny amounts of
    foods that have substantial unsaturated fatty acid content, and don't eat
    any foods that are cooked (other than boiled) that contain cholesterol.
    Switch over to coconut products. Shredded coconut (all natural), coconut
    milk (Thai kitchen's seems best), and/or coconut oil (Coconut Oil Surpreme
    seems best - tastes great - I ordered it over the internet - you can ask
    them for a free sample). Eat plenty of organic fruit. It will take at
    least a few weeks before you feel better, but it's worth not having to take
    drugs. Start to use salt to taste, but only use Celtic Sea salt. Small
    amounts of brewer's yeast (I like Twin Labs - cheap, all natural, tastes
    okay) with each meal is a good idea too. Here is an article by biochemist
    Ray Peat that may interest you:

    " Thyroid: Therapies, Confusion, and Fraud

    I. Respiratory-metabolic defect
    II. 50 years of commercially motivated fraud
    III. Tests and the "free hormone hypothesis"
    IV. Events in the tissues
    V. Therapies
    VI. Diagnosis

    VII. Respiratory defect

    Broda Barnes, more than 60 years ago, summed up the major effects of hypothyroidism on health very
    neatly when he pointed out that if hypothyroid people don't die young from infectious diseases, such
    as tuberculosis, they die a little later from cancer or heart disease. He did his PhD research at
    the University of Chicago, just a few years after Otto Warburg, in Germany, had demonstrated the
    role of a "respiratory defect" in cancer. At the time Barnes was doing his research, hypothyroidism
    was diagnosed on the basis of a low basal metabolic rate, meaning that only a small amount of oxygen
    was needed to sustain life. This deficiency of oxygen consumption involved the same enzyme system
    that Warburg was studying in cancer cells.

    Barnes experimented on rabbits, and found that when their thyroid glands were removed, they
    developed atherosclerosis, just as hypothyroid people did. By the mid-1930s, it was generally known
    that hypothyroidism causes the cholesterol level in the blood to increase; hypercholesterolemia was
    a diagnostic sign of hypothyroidism. Administering a thyroid supplement, blood cholesterol came down
    to normal exactly as the basal metabolic rate came up to the normal rate. The biology of
    atherosclerotic heart disease was basically solved before the second world war.

    Many other diseases are now known to be caused by respiratory defects. Inflammation, stress,
    immunodeficiency, autoimmunity, developmental and degenerative diseases, and aging, all involve
    significantly abnormal oxidative processes. Just brief oxygen deprivation triggers processes that
    lead to lipid peroxidation, producing a chain of other oxidative reactions when oxygen is restored.
    The only effective way to stop lipid peroxidation is to restore normal respiration.

    Now that dozens of diseases are known to involve defective respiration, the idea of thyroid's
    extremely broad range of actions is becoming easier to accept.

    VIII. 50 years of fraud

    Until the second world war, hypothyroidism was diagnosed on the basis of BMR (basal metabolic
    rate) and a large group of signs and symptoms. In the late 1940s, promotion of the (biologically
    inappropriate) PBI (protein-bound iodine) blood test in the U.S. led to the concept that only 5%
    of the population were hypothyroid, and that the 40% identified by "obsolete" methods were either
    normal, or suffered from other problems such as sloth and gluttony, or "genetic susceptibility"
    to disease.

    During the same period, thyroxine became available, and in healthy young men it acted "like the
    thyroid hormone." Older practitioners recognized that it was not metabolically the same as the
    traditional thyroid substance, especially for women and seriously hypothyroid patients, but
    marketing, and its influence on medical education, led to the false idea that the standard Armour
    thyroid USP wasn't properly standardized, and that certain thyroxine products were; despite the fact
    that both of these were shown to be false.

    By the 1960s, the PBI test was proven to be irrelevant to the diagnosis of hypothyroidism, but the
    doctrine of 5% hypothyroidism in the populaton became the basis for establishing the norms for
    biologically meaningful tests when they were introduced.

    Meanwhile, the practice of measuring serum iodine, and equating it with "thyroxine the thyroid
    hormone," led to the practice of examining only the iodine content of the putative glandular
    material that was offered for sale as thyroid USP. This led to the substitution of materials such as
    iodinated casein for desiccated thyroid in the products sold as thyroid USP. The US FDA refused to
    take action, because they held that a material's iodine content was enough to identify it as
    "thyroid USP."

    In this culture of misunderstanding and misrepresentation, the mistaken idea of hypothyroidism's low
    incidence in the population led to the acceptance of dangerously high TSH (thyroid stimulating
    hormone) activity as "normal." Just as excessive FSH (follicle stimulating hormone) has been shown
    to have a role in ovarian cancer, excessive stimulation by TSH produces disorganization in the
    thyroid gland.

    IX. Tests & the "free hormone hypothesis"

    After radioactive iodine became available, many physicians would administer a dose, and then scan
    the body with a Geiger counter, to see if it was being concentrated in the thyroid gland. If a
    person had been eating iodine-rich food (and iodine was used in bread as a preservative/dough
    condition, and was present in other foods as an accidental contaminant), they would already be over
    saturated with iodine, and the gland would fail to concentrate the iodine. The test can find some
    types of metastatic thyroid cancer, but the test generally wasn't used for that purpose. Another
    expensive and entertaining test has been the thyrotropin release hormone (TRH) test, to see if the
    pituitary responds to it by increasing TSH production. A recent study concluded that "TRH test gives
    many misleading results and has an elevated cost/benefit ratio as compared with the characteristic
    combination of low thyroxinemia and non-elevated TSH." (Bakiri, Ann. Endocr (Paris) 1999), but the
    technological drama, cost, and danger (Dokmetas, et al., J Endocrinol Invest 1999 Oct; 22(9): 698-
    700) of this test is going to make it stay popular for a long time. If the special value of the test
    is to diagnose a pituitary abnormality, it seems intuitively obvious that overstimulating the
    pituitary might not be a good idea (e.g., it could cause a tumor to grow).

    Everything else being equal, as they say, looking at the amount of thyroxine and TSH in the blood
    can be informative. The problem is that it's just a matter of faith that "everything else" is going
    to be equal. The exceptions to the "rule" regarding normal ranges for thyroxine and TSH have formed
    the basis for some theories about "the genetics of thyroid resistance," but others have pointed out
    that, when a few other things are taken into account, abnormal numbers for T4, T3, TSH, can be
    variously explained.

    The actual quantity of T3, the active thyroid hormone, in the blood can be measured with reasonable
    accuracy (using radioimmunoassay, RIA), and this single test corresponds better to the metabolic
    rate and other meaningful biological responses than other standard tests do. But still, this is only
    a statistical correspondence, and it doesn't indicate that any particular number is right for a
    particular individual.

    Sometimes, a test called the RT3U, or resin T3 uptake, is used, along with a measurement of
    thyroxine. A certain amount of radioactive T3 is added to a sample of serum, and then an adsorbent
    material is exposed to the mixture of serum and radioactive T3. The amount of radioactivity that
    sticks to the resin is called the T3 uptake. The lab report then gives a number called T7, or free
    thyroxine index. The closer this procedure is examined, the sillier it looks, and it looks pretty
    silly on its face.. The idea that the added radioactive T3 that sticks to a piece of resin will
    correspond to "free thyroxine," is in itself odd, but the really interesting question is, what do
    they mean by "free thyroxine"?

    Thyroxine is a fairly hydrophobic (insoluble in water) substance, that will associate with proteins,
    cells, and lipoproteins in the blood, rather than dissolving in the water. Although the Merck Index
    describes it as "insoluble in water," it does contain some polar groups that, in the right
    (industrial or laboratory) conditions, can make it slightly water soluble. This makes it a little
    different from progesterone, which is simply and thoroughly insoluble in water, though the term
    "free hormone" is often applied to progesterone, as it is to thyroid. In the case of progesterone,
    the term "free progesterone" can be traced to experiments in which serum containing progesterone
    (bound to proteins) is separated by a (dialysis) membrane from a solution of similar proteins which
    contain no progesterone.

    Progesterone "dissolves in" the substance of the membrane, and the serum proteins, which also tend
    to associate with the membrane, are so large that they don't pass through it. On the other side,
    proteins coming in contact with the membrane pick up some progesterone. The progesterone that
    passes through is called "free progesterone," but from that experiment, which gives no information
    on the nature of the interactions between progesterone and the dialysis membrane, or about its
    interactions with the proteins, or the proteins' interactions with the membrane, nothing is
    revealed about the reasons for the transmission or exchange of a certain amount of progesterone.
    Nevertheless, that type of experiment is used to interpret what happens in the body, where there is
    nothing that corresponds to the experimental set-up, except that some progesterone is associated
    with some protein.

    The idea that the "free hormone" is the active form has been tested in a few situations, and in the
    case of the thyroid hormone, it is clearly not true for the brain, and some other organs. The protein-
    bound hormone is, in these cases, the active form; the associations between the "free hormone" and
    the biological processes and diseases will be completely false, if they are ignoring the active
    forms of the hormone in favor of the less active forms. The conclusions will be false, as they are
    when T4 is measured, and T3 ignored. Thyroid-dependent processes will appear to be independent of
    the level of thyroid hormone; hypothyroidism could be caller hyperthyroidism.

    Although progesterone is more fat soluble than cortisol and the thyroid hormones, the behavior of
    progesterone in the blood illustrates some of the problems that have to be considered for
    interpreting thyroid physiology. When red cells are broken up, they are found to contain
    progesterone at about twice the concentration of the serum. In the serum, 40 to 80% of the
    progesterone is probably carried on albumin. (Albumin easily delivers its progesterone load into
    tissues.) Progesterone, like cholesterol, can be carried on/in the lipoproteins, in moderate
    quantities. This leaves a very small fraction to be bound to the "steroid binding globulin." Anyone
    who has tried to dissolve progesterone in various solvents and mixtures knows that it takes just a
    tiny amount of water in a solvent to make progesterone precipitate from solution as crystals; its
    solubility in water is essentially zero. "Free" progesterone would seem to mean progesterone not
    attached to proteins or dissolved in red blood cells or lipoproteins, and this would be zero. The
    tests that purport to measure free progesterone are measuring something, but not the progesterone in
    the watery fraction of the serum.

    The thyroid hormones associate with three types of simple proteins in the serum: Transthyretin
    (prealbumin), thyroid binding globulin, and albumin. A very significant amount is also associated
    with various serum lipoproteins, including HDL, LDL, and VLDL (very low density lipoproteins).

    A very large portion of the thyroid in the blood is associated with the red blood cells. When red
    cells were incubated in a medium containing serum albumin, with the cells at roughly the
    concentration found in the blood, they retained T3 at a concentration 13.5 times higher than that
    of the medium. In a larger amount of medium, their concentration of T3 was 50 times higher than the
    medium's. When laboratories measure the hormones in the serum only, they have already thrown out
    about 95% of the thyroid hormone that the blood contained.

    The T3 was found to be strongly associated with the cells' cytoplasmic proteins, but to move rapidly
    between the proteins inside the cells and other proteins outside the cells.

    When people speak of hormones travelling "on" the red blood cells, rather than "in" them, it is a
    concession to the doctrine of the impenetrable membrane barrier.

    Much more T3 bound to albumin is taken up by the liver than the small amount identified in vitro as
    free T3 (Terasaki, et al., 1987). The specific binding of T3 to albumin alters the protein's
    electrical properties, changing the way the albumin interacts with cells and other proteins.
    (Albumin becomes electrically more positive when it binds the hormone; this would make the albumin
    enter cells more easily. Giving up its T3 to the cell, it would become more negative, making it tend
    to leave the cell.) This active role of albumin in helping cells take up T3 might account for its
    increased uptake by the red cells when there were fewer cells in proportion to the albumin medium.
    This could also account for the favorable prognosis associated with higher levels of serum albumin
    in various sicknesses.

    When T3 is attached chemically (covalently, permanently) to the outside of red blood cells,
    apparently preventing its entry into other cells, the presence of these red cells produces reactions
    in other cells that are the same as some of those produced by the supposedly "free hormone." If T3
    attached to whole cells can exert its hormonal action, why should we think of the hormone bound to
    proteins as being unable to affect cells? The idea of measuring the "free hormone" is that it
    supposedly represents the biologically active hormone, but in fact it is easier to measure the
    biological effects than it is to measure this hypothetical entity. Who cares how many angels might
    be dancing on the head of a pin, if the pin is effective in keeping your shirt closed?

    . Events in the tissues

    Besides the effects of commercial deception, confusion about thyroid has resulted from some
    biological clichZs. The idea of a "barrier membrane" around cells is an assumption that has
    affected most people studying cell physiology, and its effects can be seen in nearly all of the
    thousands of publications on the functions of thyroid hormones. According to this idea, people
    have described a cell as resembling a droplet of a watery solution, enclosed in an oily bag which
    separates the internal solution from the external watery solution. The clichZ is sustained only
    by neglecting the fact that proteins have a great affinity for fats, and fats for proteins; even
    soluble proteins, such as serum albumin, often have interiors that are extremely fat-loving.
    Since the structural proteins that make up the framework of a cell aren't "dissolved in water"
    (they used to be called "the insoluble proteins"😉, the lipophilic phase isn't limited to an
    ultramicroscopically thin surface, but actually constitutes the bulk of the cell.

    Molecular geneticists like to trace their science from a 1944 experiment that was done by Avery., et
    al. Avery's group knew about an earlier experiment, that had demonstrated that when dead bacteria
    were added to living bacteria, the traits of the dead bacteria appeared in the living bacteria.
    Avery's group extracted DNA from the dead bacteria, and showed that adding it to living bacteria
    transferred the traits of the dead organisms to the living.

    In the 1930s and 1940s, the movement of huge molecules such as proteins and nucleic acids into cells
    and out of cells wasn't a big deal; people observed it happening, and wrote about it. But in the
    1940s the idea of the barrier membrane began gaining strength, and by the 1960s nothing was able to
    get into cells without authorization. At present, I doubt that any molecular geneticist would dream
    of doing a gene transplant without a "vector" to carry it across the membrane barrier.

    Since big molecules are supposed to be excluded from cells, it's only the "free hormone" which can
    find its specific port of entry into the cell, where another clichZ says it must travel into the
    nucleus, to react with a specific site to activate the specific genes through which its effects will
    be expressed.

    I don't know of any hormone that acts that way. Thyroid, progesterone, and estrogen have many
    immediate effects that change the cell's functions long before genes could be activated.

    Transthyretin, carrying the thyroid hormone, enters the cell's mitochondria and nucleus (Azimova, et
    al., 1984, 1985). In the nucleus, it immediately causes generalized changes in the structure of
    chromosomes, as if preparing the cell for major adaptive changes. Respiratory activation is
    immediate in the mitochondria, but as respiration is stimulated, everything in the cell responds,
    including the genes that support respiratory metabolism. When the membrane people have to talk about
    the entry of large molecules into cells, they use terms such as "endocytosis" and "translocases,"
    that incorporate the assumption of the barrier. But people who actually investigate the problem
    generally find that "diffusion," "codiffusion," and absorption describe the situation adequately
    (e.g., B.A. Luxon, 1997; McLeese and Eales, 1996). "Active transport" and "membrane pumps" are ideas
    that seem necessary to people who haven't studied the complex forces that operate at phase
    boundaries, such as the boundary between a cell and its environment.

    . Therapy

    Years ago it was reported that Armour thyroid, U.S.P., released T3 and T4, when digested, in a ratio
    of 1:3, and that people who used it had much higher ratios of T3 to T4 in their serum, than people
    who took only thyroxine. The argument was made that thyroxine was superior to thyroid U.S.P.,
    without explaining the significance of the fact that healthy people who weren't taking any thyroid
    supplement had higher T3:T4 ratios than the people who took thyroxine, or that our own thyroid gland
    releases a high ratio of T3 to T4. The fact that the T3 is being used faster than T4, removing it
    from the blood more quickly than it enters from the thyroid gland itself, hasn't been discussed in
    the journals, possibly because it would support the view that a natural glandular balance was more
    appropriate to supplement than pure thyroxine.

    The serum's high ratio of T4 to T3 is a pitifully poor argument to justify the use of thyroxine
    instead of a product that resembles the proportion of these substances secreted by a healthy thyroid
    gland, or maintained inside cells. About 30 years ago, when many people still thought of thyroxine
    as "the thryoid hormone," someone was making the argument that "the thyroid hormone" must work
    exclusively as an activator of genes, since most of the organ slices he tested didn't increase their
    oxygen consumption when it was added. In fact, the addition of thyroxine to brain slices suppressed
    their respiration by 6% during the experiment. Since most T3 is produced from T4 in the liver, not
    in the brain, I think that experiment had great significance, despite the ignorant interpretation of
    the author. An excess of thyroxine, in a tissue that doesn't convert it rapidly to T3, has an
    antithyroid action. (See Goumaz, et al, 1987.) This happens in many women who are given thyroxine;
    as their dose is increased, their symptoms get worse.

    The brain concentrates T3 from the serum, and may have a concentration 6 times higher than the serum
    (Goumaz, et al., 1987), and it can achieve a higher concentration of T3 than T4. It takes up and
    concentrates T3, while tending to expel T4. Reverse T3 (rT3) doesn't have much ability to enter the
    brain, but increased T4 can cause it to be produced in the brain. These observations suggest to me
    that the blood's T3:T4 ratio would be very "brain favorable" if it approached more closely to the
    ratio formed in the thyroid gland, and secreted into the blood. Although most synthetic combination
    thyroid products now use a ratio of four T4 to one T3, many people feel that their memory and
    thinking are clearer when they take a ratio of about three to one. More active metabolism probably
    keeps the blood ratio of T3 to T4 relatively high, with the liver consuming T4 at about the same
    rate that T3 is used.

    Since T3 has a short half life, it should be taken frequently. If the liver isn't producing a
    noticeable amount of T3, it is usually helpful to take a few micorgrams per hour. Since it restores
    respiration and metabolic efficiency very quickly, it isn't usually necessary to take it every hour
    or two, but until normal temperature and pulse have been achieved and stabilized, sometimes it's
    necessary to take it four or more times during the day. T4 acts by being changed to T3, so it tends
    to accumulate in the body, and on a given dose, usually reaches a steady concentration after about
    two weeks.

    An effective way to use supplements is to take a combination T4-T3 dose,
    e.g., 40 mcg of T4 and 10 mcg of T3 once a day, and to use a few mcg of T3 at other times in the
    day. Keeping a 14-day chart of pulse rate and temperature allows you to see whether the dose is
    producing the desired response. If the figures aren't increasing at all after a few days, the
    dose can be increased, until a gradual daily increment can be seen, moving toward the goal at
    the rate of about 1/14 per day

    VI. Diagnosis

    In the absence of commercial techniques that reflect thyroid physiology realistically, there is no
    valid alternative to diagnosis based on the known physiological indicators of hypothyroidism and
    hyperthyroidism. The failure to treat sick people because of one or another blood test that
    indicates "normal thyroid function," or the destruction of patients' healthy thyroid glands because
    one of the tests indicates hyperthyroidism, isn't acceptable just because it's the professional
    standard, and is enforced by benighted state licensing boards.

    Toward the end of the twentieth century, there has been considerable discussion of "evidence-based
    medicine." Good judgment requires good information, but there are forces that would over-rule
    individual judgment as to whether published information is applicable to certain patients. In an
    atmosphere that sanctions prescribing estrogen or insulin without evidence of an estrogen
    deficiency or insulin deficiency, but that penalizes practitioners who prescribe thyroid to correct
    symptoms, the published "evidence" is necessarily heavily biased. In this context, "meta-analysis"
    becomes a tool of authoritarianism, replacing the use of judgment with the improper use of
    statistical analysis.

    Unless someone can demonstrate the scientific invalidity of the methods used to diagnose
    hypothyroidism up to 1945, then they constitute the best present evidence for evaluating
    hypothyroidism, because all of the blood tests that have been used since 1950 have been.shown to be,
    at best, very crude and conceptually inappropriate methods.

    Thomas H. McGavack's 1951 book, The Thyroid, was representative of the earlier approach to the study
    of thyroid physiology. Familiarity with the different effects of abnormal thyroid function under
    different conditions, at different ages, and the effects of gender, were standard parts of medical
    education that had disappeared by the end of the century. Arthritis, irregularities of growth,
    wasting, obesity, a variety of abnormalities of the hair and skin, carotenemia, amenorrhea, tendency
    to miscarry, infertility in males and females, insomnia or somnolence, emphysema, various heart
    diseases, psychosis, dementia, poor memory, anxiety, cold extremities, anemia, and many other
    problems were known reasons to suspect hypothyroidism. If the physician didn't have a device for
    measuring oxygen consumption, estimated calorie intake could provide supporting evidence. The
    Achilles' tendon reflex was another simple objective measurement with a very strong correlation to
    the basal metabolic rate. Skin electrical resistance, or whole body impedance wasn't widely
    accepted, though it had considerable scientific validity.

    A therapeutic trial was the final test of the validity of the diagnosis: If the patient's symptoms
    disappeared as his temperature and pulse rate and food intake were normalized, the diagnostic
    hypothesis was confirmed. It was common to begin therapy with one or two grains of thyroid, and to
    adjust the dose according to the patient's response. Whatever objective indicator was used, whether
    it was basal metabolic rate, or serum cholesterol. or core temperature, or reflex relaxation rate, a
    simple chart would graphically indicate the rate of recovery toward normal health.

    Raymond Peat, Ph.D. Copyright 2000 All Rights Reserved [email hidden] www.efn.org/~raypeat

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    protein. Luxon BA, Milliano MT [The nature of thyroid hormone receptors. Intracellular functions
    of thyroxine-binding prealbumin] Azimova ShS; Normatov K; Umarova GD; Kalontarov AI; Makhmudova
    AA, Biokhimiia 1985 Nov;50(11):1926-32. The effect of tyroxin-binding prealbumin (TBPA) of blood
    serum on the template activity of chromatin was studied. It was found that the values of binding
    constants of TBPA for T3 and T4 are 2 X 10(-11) M and 5 X 10(-10) M, respectively. The receptors
    isolated from 0.4 M KCl extract of chromatin and mitochondria as well as hormone-bound TBPA cause
    similar effects on the template activity of chromatin. Based on experimental results and the
    previously published comparative data on the structure of TBPA, nuclear, cytoplasmic and
    mitochondrial receptors of thyroid hormones as well as on translocation across the plasma
    membrane and intracellular transport of TBPA, a conclusion was drawn, which suggested that TBPA
    is the "core" of the true thyroid hormone receptor. It was shown that T3-bound TBPA caused
    histone H1-dependent conformational changes in chromatin. Based on the studies with the
    interaction of the TBPA-T3 complex with spin-labeled chromatin, a scheme of functioning of the
    thyroid hormone nuclear receptor was proposed. [The nature of thyroid hormone receptors. Thyroxine-
    and triiodothyronine-binding proteins of mitochondria] Azimova ShS; Umarova GD; Petrova OS;
    Tukhtaev KR; Abdukarimov A. Biokhimiia 1984 Sep;49(9):1478-85. T4- and T3-binding proteins of rat
    liver were studied. It was found that the external mitochondrial membranes and matrix contain a
    protein whose electrophoretic mobility is similar to that of thyroxine-binding blood serum
    prealbumin (TBPA) and which binds either T4 or T3. This protein is precipitated by monospecific
    antibodies against TBPA. The internal mitochondrial membrane has two proteins able to bind
    thyroid hormones, one of which is localized in the cathode part of the gel and binds only T3,
    while the second one capable of binding T4 rather than T3 and possessing the electrophoretic
    mobility similar to that of TBPA. Radioimmunoprecipitation with monospecific antibodies against
    TBPA revealed that this protein also the antigenic determinants common with those of TBPA. The in
    vivo translocation of 125I-TBPA into submitochondrial fractions was studied. The analysis of
    densitograms of submitochondrial protein fraction showed that both TBPA and hormones are
    localized in the same protein fractions. Electron microscopic autoradiography demonstrated that
    125I-TBPA enters the cytoplasm through the external membrane and is localized on the internal
    mitochondrial membrane and matrix. [The nature of thyroid hormone receptors. Translocation of
    thyroid hormones through plasma membranes]. Azimova ShS; Umarova GD; Petrova OS; Tukhtaev KR;
    Abdukarimov A. Biokhimiia 1984 Aug;49(8):1350-6.. The in vivo translocation of thyroxine- binding
    blood serum prealbumin (TBPA) was studied. It was found that the TBPA-hormone complex penetrates-
    through the plasma membrane into the cytoplasm of target cells. Electron microscopic
    autoradiography revealed that blood serum TBPA is localized in ribosomes of target cells as well
    as in mitochondria, lipid droplets and Golgi complex. Negligible amounts of the translocated TBPA
    is localized in lysosomes of the cells insensitive to thyroid hormones (spleen macrophages).
    Study of T4- and T3-binding proteins from rat liver cytoplasm demonstrated that one of them has
    the antigenic determinants common with those of TBPA. It was shown autoimmunoradiographically
    that the structure of TBPA is not altered during its translocation. Endocrinology 1987 Apr;120(4):1590-
    6 Brain cortex reverse triiodothyronine (rT3) and triiodothyronine concentrations under steady
    state infusions of thyroxine and rT3. Goumaz MO, Kaiser CA, Burger AG. Gen Comp Endocrinol 1996
    Aug;103(2):200-8 Characteristics of the uptake of 3,5,3'-triiodo-L-thyronine and L-thyroxine into
    red blood cells of rainbow trout (Oncorhynchus mykiss). McLeese JM, Eales JG. Prog
    Neuropsychopharmacol Biol Psychiatry 1998 Feb;22(2):293-310. Increase in red blood cell
    triiodothyronine uptake in untreated unipolar major depressed patients compared to healthy
    volunteers. Moreau X, Azorin JM, Maurel M, Jeanningros R. Prog Neuropsychopharmacol Biol
    Psychiatry 1998 Feb;22(2):293-310. Increase in red blood cell triiodothyronine uptake in
    untreated unipolar major depressed patients compared to healthy volunteers. Moreau X, Azorin JM,
    Maurel M, Jeanningros R. Biochem J 1982 Oct 15;208(1):27-34. Evidence that the uptake of tri-iodo-L-
    thyronine by human erythrocytes is carrier-mediated but not energy-dependent. Docter R, Krenning
    EP, Bos G, Fekkes DF, Hennemann G. J Clin Endocrinol Metab 1990 Dec;71(6):1589-95. Transport of
    thyroid hormones by human erythrocytes: kinetic characterization in adults and newborns. Osty J,
    Valensi P, Samson M, Francon J, Blondeau JP. J Endocrinol Invest 1999 Apr;22(4):257-61. Kinetics
    of red blood cell T3 uptake in hypothyroidism with or without hormonal replacement, in the rat.
    Moreau X, Lejeune PJ, Jeanningros R. "

    Source: efn.orgthythera.rtf

  2. "nick" <[email hidden]> wrote in message news:<[email hidden]>...

    Quoted message said:

    If I were you I would do the easiest thing first. Only eat tiny amounts of foods that have
    substantial unsaturated fatty acid content, and don't eat any foods that are cooked (other than
    boiled) that contain cholesterol.

    So no cooked meat? No fried eggs?

    Quoted message said:

    Switch over to coconut products. Shredded coconut (all natural), coconut milk (Thai kitchen's
    seems best), and/or coconut oil (Coconut Oil Surpreme seems best - tastes great - I ordered it
    over the internet - you can ask them for a free sample).

    Isn't Coconut milk fattening? Coconut oil?

    Quoted message said:

    Eat plenty of organic fruit.


    I guess I need to start buy organic ones.

    Quoted message said:

    It will take at least a few weeks before you feel better, but it's worth not having to take drugs.
    Start to use salt to taste, but only use Celtic Sea salt. Small amounts of brewer's yeast (I like
    Twin Labs - cheap, all natural, tastes okay) with each meal is a good idea too.

    Will try brewer's yeats; I have heard of it.

    I have had my thyroid checked a few years ago. It was normal.

    I will read the article. Thanks a lot.

    Quoted message said:

    Here is an article by biochemist Ray Peat that may interest you:

    " Thyroid: Therapies, Confusion, and Fraud

    I. Respiratory-metabolic defect
    II. 50 years of commercially motivated fraud
    III. Tests and the "free hormone hypothesis"
    IV. Events in the tissues
    V. Therapies
    VI. Diagnosis

    I. Respiratory defect

    Broda Barnes, more than 60 years ago, summed up the major effects of hypothyroidism on health very
    neatly when he pointed out that if hypothyroid people don't die young from infectious diseases,
    such as tuberculosis, they die a little later from cancer or heart disease. He did his PhD
    research at the University of Chicago, just a few years after Otto Warburg, in Germany, had
    demonstrated the role of a "respiratory defect" in cancer. At the time Barnes was doing his
    research, hypothyroidism was diagnosed on the basis of a low basal metabolic rate, meaning that
    only a small amount of oxygen was needed to sustain life. This deficiency of oxygen consumption
    involved the same enzyme system that Warburg was studying in cancer cells.

    Barnes experimented on rabbits, and found that when their thyroid glands were removed, they
    developed atherosclerosis, just as hypothyroid people did. By the mid-1930s, it was generally
    known that hypothyroidism causes the cholesterol level in the blood to increase;
    hypercholesterolemia was a diagnostic sign of hypothyroidism. Administering a thyroid
    supplement, blood cholesterol came down to normal exactly as the basal metabolic rate came up to
    the normal rate. The biology of atherosclerotic heart disease was basically solved before the
    second world war.

    Many other diseases are now known to be caused by respiratory defects. Inflammation, stress,
    immunodeficiency, autoimmunity, developmental and degenerative diseases, and aging, all involve
    significantly abnormal oxidative processes. Just brief oxygen deprivation triggers processes that
    lead to lipid peroxidation, producing a chain of other oxidative reactions when oxygen is
    restored. The only effective way to stop lipid peroxidation is to restore normal respiration.

    Now that dozens of diseases are known to involve defective respiration, the idea of thyroid's
    extremely broad range of actions is becoming easier to accept.

    II. 50 years of fraud

    Until the second world war, hypothyroidism was diagnosed on the basis of BMR (basal metabolic
    rate) and a large group of signs and symptoms. In the late 1940s, promotion of the (biologically
    inappropriate) PBI (protein-bound iodine) blood test in the U.S. led to the concept that only 5%
    of the population were hypothyroid, and that the 40% identified by "obsolete" methods were either
    normal, or suffered from other problems such as sloth and gluttony, or "genetic susceptibility" to
    disease.

    During the same period, thyroxine became available, and in healthy young men it acted "like the
    thyroid hormone." Older practitioners recognized that it was not metabolically the same as the
    traditional thyroid substance, especially for women and seriously hypothyroid patients, but
    marketing, and its influence on medical education, led to the false idea that the standard Armour
    thyroid USP wasn't properly standardized, and that certain thyroxine products were; despite the
    fact that both of these were shown to be false.

    By the 1960s, the PBI test was proven to be irrelevant to the diagnosis of hypothyroidism, but the
    doctrine of 5% hypothyroidism in the populaton became the basis for establishing the norms for
    biologically meaningful tests when they were introduced.

    Meanwhile, the practice of measuring serum iodine, and equating it with "thyroxine the thyroid
    hormone," led to the practice of examining only the iodine content of the putative glandular
    material that was offered for sale as thyroid USP. This led to the substitution of materials such
    as iodinated casein for desiccated thyroid in the products sold as thyroid USP. The US FDA refused
    to take action, because they held that a material's iodine content was enough to identify it as
    "thyroid USP."

    In this culture of misunderstanding and misrepresentation, the mistaken idea of hypothyroidism's
    low incidence in the population led to the acceptance of dangerously high TSH (thyroid stimulating
    hormone) activity as "normal." Just as excessive FSH (follicle stimulating hormone) has been shown
    to have a role in ovarian cancer, excessive stimulation by TSH produces disorganization in the
    thyroid gland.

    III. Tests & the "free hormone hypothesis"

    After radioactive iodine became available, many physicians would administer a dose, and then scan
    the body with a Geiger counter, to see if it was being concentrated in the thyroid gland. If a
    person had been eating iodine-rich food (and iodine was used in bread as a preservative/dough
    condition, and was present in other foods as an accidental contaminant), they would already be
    over saturated with iodine, and the gland would fail to concentrate the iodine. The test can find
    some types of metastatic thyroid cancer, but the test generally wasn't used for that purpose.
    Another expensive and entertaining test has been the thyrotropin release hormone (TRH) test, to
    see if the pituitary responds to it by increasing TSH production. A recent study concluded that
    "TRH test gives many misleading results and has an elevated cost/benefit ratio as compared with
    the characteristic combination of low thyroxinemia and non-elevated TSH." (Bakiri, Ann. Endocr
    (Paris) 1999), but the technological drama, cost, and danger (Dokmetas, et al., J Endocrinol
    Invest 1999 Oct; 22(9): 698-700) of this test is going to make it stay popular for a long time.
    If the special value of the test is to diagnose a pituitary abnormality, it seems intuitively
    obvious that overstimulating the pituitary might not be a good idea (e.g., it could cause a tumor
    to grow).

    Everything else being equal, as they say, looking at the amount of thyroxine and TSH in the blood
    can be informative. The problem is that it's just a matter of faith that "everything else" is
    going to be equal. The exceptions to the "rule" regarding normal ranges for thyroxine and TSH have
    formed the basis for some theories about "the genetics of thyroid resistance," but others have
    pointed out that, when a few other things are taken into account, abnormal numbers for T4, T3,
    TSH, can be variously explained.

    The actual quantity of T3, the active thyroid hormone, in the blood can be measured with
    reasonable accuracy (using radioimmunoassay, RIA), and this single test corresponds better to the
    metabolic rate and other meaningful biological responses than other standard tests do. But still,
    this is only a statistical correspondence, and it doesn't indicate that any particular number is
    right for a particular individual.

    Sometimes, a test called the RT3U, or resin T3 uptake, is used, along with a measurement of
    thyroxine. A certain amount of radioactive T3 is added to a sample of serum, and then an adsorbent
    material is exposed to the mixture of serum and radioactive T3. The amount of radioactivity that
    sticks to the resin is called the T3 uptake. The lab report then gives a number called T7, or free
    thyroxine index. The closer this procedure is examined, the sillier it looks, and it looks pretty
    silly on its face.. The idea that the added radioactive T3 that sticks to a piece of resin will
    correspond to "free thyroxine," is in itself odd, but the really interesting question is, what do
    they mean by "free thyroxine"?

    Thyroxine is a fairly hydrophobic (insoluble in water) substance, that will associate with
    proteins, cells, and lipoproteins in the blood, rather than dissolving in the water. Although the
    Merck Index describes it as "insoluble in water," it does contain some polar groups that, in the
    right (industrial or laboratory) conditions, can make it slightly water soluble. This makes it a
    little different from progesterone, which is simply and thoroughly insoluble in water, though the
    term "free hormone" is often applied to progesterone, as it is to thyroid. In the case of
    progesterone, the term "free progesterone" can be traced to experiments in which serum containing
    progesterone (bound to proteins) is separated by a (dialysis) membrane from a solution of similar
    proteins which contain no progesterone.

    Progesterone "dissolves in" the substance of the membrane, and the serum proteins, which also tend
    to associate with the membrane, are so large that they don't pass through it. On the other side,
    proteins coming in contact with the membrane pick up some progesterone. The progesterone that
    passes through is called "free progesterone," but from that experiment, which gives no information
    on the nature of the interactions between progesterone and the dialysis membrane, or about its
    interactions with the proteins, or the proteins' interactions with the membrane, nothing is
    revealed about the reasons for the transmission or exchange of a certain amount of progesterone.
    Nevertheless, that type of experiment is used to interpret what happens in the body, where there
    is nothing that corresponds to the experimental set-up, except that some progesterone is
    associated with some protein.

    The idea that the "free hormone" is the active form has been tested in a few situations, and in
    the case of the thyroid hormone, it is clearly not true for the brain, and some other organs. The
    protein-bound hormone is, in these cases, the active form; the associations between the "free
    hormone" and the biological processes and diseases will be completely false, if they are ignoring
    the active forms of the hormone in favor of the less active forms. The conclusions will be false,
    as they are when T4 is measured, and T3 ignored. Thyroid-dependent processes will appear to be
    independent of the level of thyroid hormone; hypothyroidism could be caller hyperthyroidism.

    Although progesterone is more fat soluble than cortisol and the thyroid hormones, the behavior of
    progesterone in the blood illustrates some of the problems that have to be considered for
    interpreting thyroid physiology. When red cells are broken up, they are found to contain
    progesterone at about twice the concentration of the serum. In the serum, 40 to 80% of the
    progesterone is probably carried on albumin. (Albumin easily delivers its progesterone load into
    tissues.) Progesterone, like cholesterol, can be carried on/in the lipoproteins, in moderate
    quantities. This leaves a very small fraction to be bound to the "steroid binding globulin."
    Anyone who has tried to dissolve progesterone in various solvents and mixtures knows that it takes
    just a tiny amount of water in a solvent to make progesterone precipitate from solution as
    crystals; its solubility in water is essentially zero. "Free" progesterone would seem to mean
    progesterone not attached to proteins or dissolved in red blood cells or lipoproteins, and this
    would be zero. The tests that purport to measure free progesterone are measuring something, but
    not the progesterone in the watery fraction of the serum.

    The thyroid hormones associate with three types of simple proteins in the serum: Transthyretin
    (prealbumin), thyroid binding globulin, and albumin. A very significant amount is also associated
    with various serum lipoproteins, including HDL, LDL, and VLDL (very low density lipoproteins).

    A very large portion of the thyroid in the blood is associated with the red blood cells. When red
    cells were incubated in a medium containing serum albumin, with the cells at roughly the
    concentration found in the blood, they retained T3 at a concentration 13.5 times higher than that
    of the medium. In a larger amount of medium, their concentration of T3 was 50 times higher than
    the medium's. When laboratories measure the hormones in the serum only, they have already thrown
    out about 95% of the thyroid hormone that the blood contained.

    The T3 was found to be strongly associated with the cells' cytoplasmic proteins, but to move
    rapidly between the proteins inside the cells and other proteins outside the cells.

    When people speak of hormones travelling "on" the red blood cells, rather than "in" them, it is a
    concession to the doctrine of the impenetrable membrane barrier.

    Much more T3 bound to albumin is taken up by the liver than the small amount identified in vitro
    as free T3 (Terasaki, et al., 1987). The specific binding of T3 to albumin alters the protein's
    electrical properties, changing the way the albumin interacts with cells and other proteins.
    (Albumin becomes electrically more positive when it binds the hormone; this would make the albumin
    enter cells more easily. Giving up its T3 to the cell, it would become more negative, making it
    tend to leave the cell.) This active role of albumin in helping cells take up T3 might account for
    its increased uptake by the red cells when there were fewer cells in proportion to the albumin
    medium. This could also account for the favorable prognosis associated with higher levels of serum
    albumin in various sicknesses.

    When T3 is attached chemically (covalently, permanently) to the outside of red blood cells,
    apparently preventing its entry into other cells, the presence of these red cells produces
    reactions in other cells that are the same as some of those produced by the supposedly "free
    hormone." If T3 attached to whole cells can exert its hormonal action, why should we think of the
    hormone bound to proteins as being unable to affect cells? The idea of measuring the "free
    hormone" is that it supposedly represents the biologically active hormone, but in fact it is
    easier to measure the biological effects than it is to measure this hypothetical entity. Who cares
    how many angels might be dancing on the head of a pin, if the pin is effective in keeping your
    shirt closed?

    IV. Events in the tissues

    Besides the effects of commercial deception, confusion about thyroid has resulted from some
    biological clichZs. The idea of a "barrier membrane" around cells is an assumption that has
    affected most people studying cell physiology, and its effects can be seen in nearly all of the
    thousands of publications on the functions of thyroid hormones. According to this idea, people
    have described a cell as resembling a droplet of a watery solution, enclosed in an oily bag
    which separates the internal solution from the external watery solution. The clichZ is
    sustained only by neglecting the fact that proteins have a great affinity for fats, and fats
    for proteins; even soluble proteins, such as serum albumin, often have interiors that are
    extremely fat-loving. Since the structural proteins that make up the framework of a cell aren't
    "dissolved in water" (they used to be called "the insoluble proteins"😉, the lipophilic phase
    isn't limited to an ultramicroscopically thin surface, but actually constitutes the bulk of the
    cell.

    Molecular geneticists like to trace their science from a 1944 experiment that was done by Avery.,
    et al. Avery's group knew about an earlier experiment, that had demonstrated that when dead
    bacteria were added to living bacteria, the traits of the dead bacteria appeared in the living
    bacteria. Avery's group extracted DNA from the dead bacteria, and showed that adding it to living
    bacteria transferred the traits of the dead organisms to the living.

    In the 1930s and 1940s, the movement of huge molecules such as proteins and nucleic acids into
    cells and out of cells wasn't a big deal; people observed it happening, and wrote about it. But in
    the 1940s the idea of the barrier membrane began gaining strength, and by the 1960s nothing was
    able to get into cells without authorization. At present, I doubt that any molecular geneticist
    would dream of doing a gene transplant without a "vector" to carry it across the membrane barrier.

    Since big molecules are supposed to be excluded from cells, it's only the "free hormone" which can
    find its specific port of entry into the cell, where another clichZ says it must travel into the
    nucleus, to react with a specific site to activate the specific genes through which its effects
    will be expressed.

    I don't know of any hormone that acts that way. Thyroid, progesterone, and estrogen have many
    immediate effects that change the cell's functions long before genes could be activated.

    Transthyretin, carrying the thyroid hormone, enters the cell's mitochondria and nucleus (Azimova,
    et al., 1984, 1985). In the nucleus, it immediately causes generalized changes in the structure of
    chromosomes, as if preparing the cell for major adaptive changes. Respiratory activation is
    immediate in the mitochondria, but as respiration is stimulated, everything in the cell responds,
    including the genes that support respiratory metabolism. When the membrane people have to talk
    about the entry of large molecules into cells, they use terms such as "endocytosis" and
    "translocases," that incorporate the assumption of the barrier. But people who actually
    investigate the problem generally find that "diffusion," "codiffusion," and absorption describe
    the situation adequately (e.g., B.A. Luxon, 1997; McLeese and Eales, 1996). "Active transport" and
    "membrane pumps" are ideas that seem necessary to people who haven't studied the complex forces
    that operate at phase boundaries, such as the boundary between a cell and its environment.

    V. Therapy

    Years ago it was reported that Armour thyroid, U.S.P., released T3 and T4, when digested, in a
    ratio of 1:3, and that people who used it had much higher ratios of T3 to T4 in their serum, than
    people who took only thyroxine. The argument was made that thyroxine was superior to thyroid
    U.S.P., without explaining the significance of the fact that healthy people who weren't taking any
    thyroid supplement had higher T3:T4 ratios than the people who took thyroxine, or that our own
    thyroid gland releases a high ratio of T3 to T4. The fact that the T3 is being used faster than
    T4, removing it from the blood more quickly than it enters from the thyroid gland itself, hasn't
    been discussed in the journals, possibly because it would support the view that a natural
    glandular balance was more appropriate to supplement than pure thyroxine.

    The serum's high ratio of T4 to T3 is a pitifully poor argument to justify the use of thyroxine
    instead of a product that resembles the proportion of these substances secreted by a healthy
    thyroid gland, or maintained inside cells. About 30 years ago, when many people still thought of
    thyroxine as "the thryoid hormone," someone was making the argument that "the thyroid hormone"
    must work exclusively as an activator of genes, since most of the organ slices he tested didn't
    increase their oxygen consumption when it was added. In fact, the addition of thyroxine to brain
    slices suppressed their respiration by 6% during the experiment. Since most T3 is produced from T4
    in the liver, not in the brain, I think that experiment had great significance, despite the
    ignorant interpretation of the author. An excess of thyroxine, in a tissue that doesn't convert it
    rapidly to T3, has an antithyroid action. (See Goumaz, et al, 1987.) This happens in many women
    who are given thyroxine; as their dose is increased, their symptoms get worse.

    The brain concentrates T3 from the serum, and may have a concentration 6 times higher than the
    serum (Goumaz, et al., 1987), and it can achieve a higher concentration of T3 than T4. It takes up
    and concentrates T3, while tending to expel T4. Reverse T3 (rT3) doesn't have much ability to
    enter the brain, but increased T4 can cause it to be produced in the brain. These observations
    suggest to me that the blood's T3:T4 ratio would be very "brain favorable" if it approached more
    closely to the ratio formed in the thyroid gland, and secreted into the blood. Although most
    synthetic combination thyroid products now use a ratio of four T4 to one T3, many people feel that
    their memory and thinking are clearer when they take a ratio of about three to one. More active
    metabolism probably keeps the blood ratio of T3 to T4 relatively high, with the liver consuming T4
    at about the same rate that T3 is used.

    Since T3 has a short half life, it should be taken frequently. If the liver isn't producing a
    noticeable amount of T3, it is usually helpful to take a few micorgrams per hour. Since it
    restores respiration and metabolic efficiency very quickly, it isn't usually necessary to take it
    every hour or two, but until normal temperature and pulse have been achieved and stabilized,
    sometimes it's necessary to take it four or more times during the day. T4 acts by being changed to
    T3, so it tends to accumulate in the body, and on a given dose, usually reaches a steady
    concentration after about two weeks.

    An effective way to use supplements is to take a combination T4-T3 dose,
    e.g., 40 mcg of T4 and 10 mcg of T3 once a day, and to use a few mcg of T3 at other times in the
    day. Keeping a 14-day chart of pulse rate and temperature allows you to see whether the dose
    is producing the desired response. If the figures aren't increasing at all after a few days,
    the dose can be increased, until a gradual daily increment can be seen, moving toward the goal
    at the rate of about 1/14 per day

    VI. Diagnosis

    In the absence of commercial techniques that reflect thyroid physiology realistically, there is no
    valid alternative to diagnosis based on the known physiological indicators of hypothyroidism and
    hyperthyroidism. The failure to treat sick people because of one or another blood test that
    indicates "normal thyroid function," or the destruction of patients' healthy thyroid glands
    because one of the tests indicates hyperthyroidism, isn't acceptable just because it's the
    professional standard, and is enforced by benighted state licensing boards.

    Toward the end of the twentieth century, there has been considerable discussion of "evidence-based
    medicine." Good judgment requires good information, but there are forces that would over-rule
    individual judgment as to whether published information is applicable to certain patients. In an
    atmosphere that sanctions prescribing estrogen or insulin without evidence of an estrogen
    deficiency or insulin deficiency, but that penalizes practitioners who prescribe thyroid to
    correct symptoms, the published "evidence" is necessarily heavily biased. In this context, "meta-
    analysis" becomes a tool of authoritarianism, replacing the use of judgment with the improper use
    of statistical analysis.

    Unless someone can demonstrate the scientific invalidity of the methods used to diagnose
    hypothyroidism up to 1945, then they constitute the best present evidence for evaluating
    hypothyroidism, because all of the blood tests that have been used since 1950 have been.shown to
    be, at best, very crude and conceptually inappropriate methods.

    Thomas H. McGavack's 1951 book, The Thyroid, was representative of the earlier approach to the
    study of thyroid physiology. Familiarity with the different effects of abnormal thyroid function
    under different conditions, at different ages, and the effects of gender, were standard parts of
    medical education that had disappeared by the end of the century. Arthritis, irregularities of
    growth, wasting, obesity, a variety of abnormalities of the hair and skin, carotenemia,
    amenorrhea, tendency to miscarry, infertility in males and females, insomnia or somnolence,
    emphysema, various heart diseases, psychosis, dementia, poor memory, anxiety, cold extremities,
    anemia, and many other problems were known reasons to suspect hypothyroidism. If the physician
    didn't have a device for measuring oxygen consumption, estimated calorie intake could provide
    supporting evidence. The Achilles' tendon reflex was another simple objective measurement with a
    very strong correlation to the basal metabolic rate. Skin electrical resistance, or whole body
    impedance wasn't widely accepted, though it had considerable scientific validity.

    A therapeutic trial was the final test of the validity of the diagnosis: If the patient's
    symptoms disappeared as his temperature and pulse rate and food intake were normalized, the
    diagnostic hypothesis was confirmed. It was common to begin therapy with one or two grains of
    thyroid, and to adjust the dose according to the patient's response. Whatever objective indicator
    was used, whether it was basal metabolic rate, or serum cholesterol. or core temperature, or
    reflex relaxation rate, a simple chart would graphically indicate the rate of recovery toward
    normal health.

    Raymond Peat, Ph.D. Copyright 2000 All Rights Reserved [email hidden] www.efn.org/~raypeat

    REFERENCES

    McGavack, Thomas Hodge.: The thyroid,: St. Louis, Mosby, 1951. 646 p. ill.Several chapters
    contributed by various authors.Call Numbers WK200 M145t 1951 (Rare Book). Endocrinology 1979 Sep;
    105(3): 605-12. Carrier-mediated transport of thyroid hormones through the rat blood-brain
    barrier: primary role of albumin-bound hormone. Pardridge WM. Endocrinology 1987 Apr;120(4):1590-
    6. Brain cortex reverse triiodothyronine (rT3) and triiodothyronine concentrations under steady
    state infusions of thyroxine and rT3. Goumaz MO, Kaiser CA, Burger A.G. J Clin Invest 1984 Sep;74(3):745-
    52. Tracer kinetic model of blood-brain barrier transport of plasma protein-bound ligands. Empiric
    testing of the free hormone hypothesis. Pardridge WM, Landaw EM. Previous studies have shown that
    the fraction of hormone or drug that is plasma protein bound is readily available for transport
    through the brain endothelial wall, i.e., the blood-brain barrier (BBB). To test whether these
    observations are reconcilable with the free-hormone hypothesis, a tracer-kinetic model is used
    Endocrinology 113(1), 391-8, 1983, Stimulation of sugar transport in cultured heart cells by
    triiodothyronine (T2) covalently bound to red blood cells and by T3 in the presence of serum,
    Dickstein Y, Schwartz H, Gross J, Gordon A. Endocrinology 1987 Sep; 121(3): 1185-91.
    Stereospecificity of triiodothyronine transport into brain, liver, and salivary gland: role of carrier-
    and plasma protein-mediated transport. Terasaki T, Pardridge WM.
    J. Neurophysiol 1994 Jul;72(1):380-91. Film autoradiography identifies unique features of [125I]3,3'5'-
    (reverse) triiodothyronine transport from blood to brain. Cheng LY, Outterbridge LV, Covatta
    ND, Martens DA, Gordon JT, Dratman MB Brain Res 1991 Jul 19;554(1-2):229-36. Transport of
    iodothyronines from bloodstream to brain: contributions by blood:brain and choroid
    plexus:cerebrospinal fluid barriers. Dratman MB, Crutchfield FL, Schoenhoff
    MB.. Mech Ageing Dev 1990 Mar 15;52(2-3):141-7. Blood-brain transport of triiodothyronine is
    reduced in aged rats. Mooradian AD Geriatrics Section, Tucson VA Medical Center, AZ.
    Endocrinology 1987 Sep;121(3):1185-91. Stereospecificity of triiodothyronine transport into
    brain, liver, and salivary gland: role of carrier- and plasma protein-mediated transport.
    Terasaki T, Pardridge WM. J Clin Invest 1984 Sep;74(3):745-52. Tracer kinetic model of blood-
    brain barrier transport of plasma protein-bound ligands. Empiric testing of the free hormone
    hypothesis. Pardridge WM, Landaw EM. Endocrinology 1980 Dec;107(6):1705-10. Transport of
    thyroid and steroid hormones through the blood-brain barrier of the newborn rabbit: primary
    role of protein-bound hormone. Pardridge WM, Mietus LJ. Endocrinology 1979 Sep; 105(3): 605-12.
    Carrier-mediated transport of thyroid hormones through the rat blood-brain barrier: primary
    role of albumin-bound hormone. Pardridge WM. Endocrinology 1975 Jun;96(6):1357-65.
    Triiodothyronine binding in rat anterior pituitary, posterior pituitary, median eminence and
    brain. Gordon A, Spira O. Endocr Rev 1989 Aug;10(3):232-74. The free hormone hypothesis: a
    physiologically based mathematical model. Mendel CM. Biochim Biophys Acta 1991 Mar 4;1073(2):275-
    84. Transport of steroid hormones facilitated by serum proteins. Watanabe S, Tani T, Watanabe
    S, Seno M Kanagawa. D Novitzky, H Fontanet, M Snyder, N Coblio, D Smith, V Parsonnet, Impact of
    triiodothyronine on the survival of high-risk patients undergoing open heart surgery,
    Cardiology, 1996, Vol 87, Iss 6, pp 509-515. Biochim Biophys Acta 1997. Jan 16;1318(1-2):173-83
    Regulation of the energy coupling in mitochondria by some steroid and thyroid hormones. Starkov
    AA, Simonyan RA, Dedukhova VI, Mansurova SE, Palamarchuk LA, Skulachev VP Thyroid 1996 Oct;6(5):531-
    6. Novel actions of thyroid hormone: the role of triiodothyronine in cardiac transplantation.
    Novitzky D. Rev Med Chil 1996 Oct;124(10):1248-50. [Severe cardiac failure as complication of
    primary hypothyroidism]. Novik V, Cardenas IE, Gonzalez R, Pena M, Lopez Moreno JM. Cardiology
    1996 Nov-Dec;87(6):509-15. Impact of triiodothyronine on the survival of high-risk patients
    undergoing open heart surgery. Novitzky D, Fontanet H, Snyder M, Coblio N, Smith D, Parsonnet V
    Curr Opin Cardiol 1996 Nov;11(6):603-9. The use of thyroid hormone in cardiac surgery. Dyke C N
    Koibuchi, S Matsuzaki, K Ichimura, H Ohtake, S Yamaoka. Ontogenic changes in the expression of
    cytochrome c oxidase subunit I gene in the cerebellar cortex of the perinatal hypothyroid rat.
    Endocrinology, 1996, Vol 137, Iss 11, pp 5096-5108. Biokhimiia 1984 Aug;49(8):1350-6. [The
    nature of thyroid hormone receptors. Translocation of thyroid hormones through plasma
    membranes]. [Article in Russian] Azimova ShS, Umarova GD, Petrova OS, Tukhtaev KR, Abdukarimov
    A. The in vivo translocation of thyroxine-binding blood serum prealbumin (TBPA) was studied. It
    was found that the TBPA-hormone complex penetrates-through the plasma membrane into the
    cytoplasm of target cells. Electron microscopic autoradiography revealed that blood serum TBPA
    is localized in ribosomes of target cells as well as in mitochondria, lipid droplets and Golgi
    complex. Negligible amounts of the translocated TBPA is localized in lysosomes of the cells
    insensitive to thyroid hormones (spleen macrophages). Study of T4- and T3-binding proteins from
    rat liver cytoplasm demonstrated that one of them has the antigenic determinants common with
    those of TBPA. It was shown autoimmunoradiographically that the structure of TBPA is not
    altered during its translocation. Am J Physiol 1997 Sep;273(3 Pt 1):C859-67. Cytoplasmic
    codiffusion of fatty acids is not specific for fatty acid binding protein. Luxon BA, Milliano
    MT [The nature of thyroid hormone receptors. Intracellular functions of thyroxine-binding
    prealbumin] Azimova ShS; Normatov K; Umarova GD; Kalontarov AI; Makhmudova AA, Biokhimiia 1985
    Nov;50(11):1926-32. The effect of tyroxin-binding prealbumin (TBPA) of blood serum on the
    template activity of chromatin was studied. It was found that the values of binding constants
    of TBPA for T3 and T4 are 2 X 10(-11) M and 5 X 10(-10) M, respectively. The receptors isolated
    from 0.4 M KCl extract of chromatin and mitochondria as well as hormone-bound TBPA cause
    similar effects on the template activity of chromatin. Based on experimental results and the
    previously published comparative data on the structure of TBPA, nuclear, cytoplasmic and
    mitochondrial receptors of thyroid hormones as well as on translocation across the plasma
    membrane and intracellular transport of TBPA, a conclusion was drawn, which suggested that TBPA
    is the "core" of the true thyroid hormone receptor. It was shown that T3-bound TBPA caused
    histone H1-dependent conformational changes in chromatin. Based on the studies with the
    interaction of the TBPA-T3 complex with spin-labeled chromatin, a scheme of functioning of the
    thyroid hormone nuclear receptor was proposed. [The nature of thyroid hormone receptors. Thyroxine-
    and triiodothyronine-binding proteins of mitochondria] Azimova ShS; Umarova GD; Petrova OS;
    Tukhtaev KR; Abdukarimov A. Biokhimiia 1984 Sep;49(9):1478-85. T4- and T3-binding proteins of
    rat liver were studied. It was found that the external mitochondrial membranes and matrix
    contain a protein whose electrophoretic mobility is similar to that of thyroxine-binding blood
    serum prealbumin (TBPA) and which binds either T4 or T3. This protein is precipitated by
    monospecific antibodies against TBPA. The internal mitochondrial membrane has two proteins able
    to bind thyroid hormones, one of which is localized in the cathode part of the gel and binds
    only T3, while the second one capable of binding T4 rather than T3 and possessing the
    electrophoretic mobility similar to that of TBPA. Radioimmunoprecipitation with monospecific
    antibodies against TBPA revealed that this protein also the antigenic determinants common with
    those of TBPA. The in vivo translocation of 125I-TBPA into submitochondrial fractions was
    studied. The analysis of densitograms of submitochondrial protein fraction showed that both
    TBPA and hormones are localized in the same protein fractions. Electron microscopic
    autoradiography demonstrated that 125I-TBPA enters the cytoplasm through the external membrane
    and is localized on the internal mitochondrial membrane and matrix. [The nature of thyroid
    hormone receptors. Translocation of thyroid hormones through plasma membranes]. Azimova ShS;
    Umarova GD; Petrova OS; Tukhtaev KR; Abdukarimov A. Biokhimiia 1984 Aug;49(8):1350-6.. The in
    vivo translocation of thyroxine- binding blood serum prealbumin (TBPA) was studied. It was
    found that the TBPA-hormone complex penetrates-through the plasma membrane into the cytoplasm
    of target cells. Electron microscopic autoradiography revealed that blood serum TBPA is
    localized in ribosomes of target cells as well as in mitochondria, lipid droplets and Golgi
    complex. Negligible amounts of the translocated TBPA is localized in lysosomes of the cells
    insensitive to thyroid hormones (spleen macrophages). Study of T4- and T3-binding proteins from
    rat liver cytoplasm demonstrated that one of them has the antigenic determinants common with
    those of TBPA. It was shown autoimmunoradiographically that the structure of TBPA is not
    altered during its translocation. Endocrinology 1987 Apr;120(4):1590-6 Brain cortex reverse
    triiodothyronine (rT3) and triiodothyronine concentrations under steady state infusions of
    thyroxine and rT3. Goumaz MO, Kaiser CA, Burger AG. Gen Comp Endocrinol 1996 Aug;103(2):200-8
    Characteristics of the uptake of 3,5,3'-triiodo-L-thyronine and L-thyroxine into red blood
    cells of rainbow trout (Oncorhynchus mykiss). McLeese JM, Eales JG. Prog Neuropsychopharmacol
    Biol Psychiatry 1998 Feb;22(2):293-310. Increase in red blood cell triiodothyronine uptake in
    untreated unipolar major depressed patients compared to healthy volunteers. Moreau X, Azorin
    JM, Maurel M, Jeanningros R. Prog Neuropsychopharmacol Biol Psychiatry 1998 Feb;22(2):293-310.
    Increase in red blood cell triiodothyronine uptake in untreated unipolar major depressed
    patients compared to healthy volunteers. Moreau X, Azorin JM, Maurel M, Jeanningros R. Biochem
    J 1982 Oct 15;208(1):27-34. Evidence that the uptake of tri-iodo-L-thyronine by human
    erythrocytes is carrier-mediated but not energy-dependent. Docter R, Krenning EP, Bos G, Fekkes
    DF, Hennemann G. J Clin Endocrinol Metab 1990 Dec;71(6):1589-95. Transport of thyroid hormones
    by human erythrocytes: kinetic characterization in adults and newborns. Osty J, Valensi P,
    Samson M, Francon J, Blondeau JP. J Endocrinol Invest 1999 Apr;22(4):257-61. Kinetics of red
    blood cell T3 uptake in hypothyroidism with or without hormonal replacement, in the rat. Moreau
    X, Lejeune PJ, Jeanningros R. "

    Source: efn.orgthythera.rtf

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