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<html>
<head><title>Thyroid: Therapies, Confusion, and Fraud</title></head>
<body>
<h1>
Thyroid: Therapies, Confusion, and Fraud
</h1>
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
<strong>I. Respiratory defect</strong>
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.
<strong>II. 50 years of fraud</strong>
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.
<strong>III. Tests &amp; the "free hormone hypothesis"</strong>
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?
<strong>IV. Events in the tissues</strong>
Besides the effects of commercial deception, confusion about thyroid has resulted from some biological clich"s.
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
clich" 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 clich" 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.
<strong>V. Therapy</strong>
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
<strong>VI. Diagnosis</strong>
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.
<strong><h3>REFERENCES</h3></strong>
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Carrier-mediated transport of thyroid hormones through the rat blood-brain barrier: primary role of
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(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
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Endocrinology 1987 Sep; 121(3): 1185-91. Stereospecificity of triiodothyronine transport into brain, liver, and
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Neurophysiol 1994 Jul;72(1):380-91. Film autoradiography identifies unique features of [125I]3,3'5'-(reverse)
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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.
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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
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