THYROXINE - 3,5,3', 5 '-tetrayodtironin (T4), the iodated aminocarboxylic acid, derivative amino acids of tyrosine (or yodgorgonovy acid of diiodotyrosine), the main hormone of a thyroid gland, is the main circulating form of thyroid hormones.
T. possesses diverse fiziol. action: it is necessary for the normal growth, development and differentiation of fabrics, stimulates cordial activity, proteinaceous, carbohydrate and the lipometabolism, carrying out nervous impulses, strengthens oxygen absorption fabrics and their heat production, increases activity of separate fermental systems both in the whole organism, and in culture of fabrics. Usually answer to T. comes after a certain stage of latency and it is shown by strengthening of metabolism in a liver, heart, muscles and kidneys, however in some other bodies (a brain of the adult, a spleen, seed bubbles) of the changes of metabolism caused by T., it is not revealed.
On a share of T. 3/4 all iodine, contained in blood are necessary (see. Iodine ). T. it is allocated in blood after hydrolysis of thyreoglobulin (see) proteases of lysosomes of follicular cells of a thyroid gland (see). L-isomer T. possesses fiziol. the activity, by 3 times exceeding activity of its D-isomer.
Biosynthesis of T. occurs by condensation of two molecules of a diyodgiroznn in a molecule of thyreoglobulin (see. Yodtirozina ), in detail mechanism of biosynthesis of T. it is not found out, the conventional hypothesis assumes oxidation of a molecule of diiodotyrosine to the free radical and formation of T. through hinonovy ether. At the same time two molecules of diiodotyrosine which are in the connected state interact; the T formed as a result of reaction. and degidroalanin or serine remain in a molecule of thyreoglobulin. Allow also other option: the diiodotyrosine which is in the tpreoglobulena enters coupling reaction with a free molecule 3,5 '-diiodine-4-oxyphenyl-pyroracemic to - you.
Secretions of T. in blood gradual hydrolysis of molecules of thyreoglobulin in lysosomes of follicular cells of a thyroid gland at their migration in the direction of a basal membrane of a follicular cell precedes.
T. in a thyroid gland is exposed to partial deiodinating under the influence of a specific deyodaza, excellent from iodtyrosine-deyodazy (KF 126.96.36.199), with education 3,5,3 '-trpyodtironina (see Yodtyronina) and 3,3'5' - triiodothyronine — so-called return triiodothyronine (from 3 ), to-rye also cosecrete in blood. In a thyroid gland of the adult in days 87 mkg of thyroxine are on average developed, from to-rykh 8 mkg turn in triiodothyronine (see) — T3, 0,9 mkg — in from 3 , and the ground mass of hormone comes to a blood stream without changes.
Tireondny hormones (T3 and T4) circulate in blood generally in the form of complexes with proteins of serum (see. Proteinaceous and connected iodine ). Among the serum proteins connecting T., it is necessary to secrete especially tiroksinsvyazyvayushchy proteins (TSB) — globulin and prealbumin. T. in a complex with prealbumin possesses bigger biol. activity, than free hormone.
Concentration circulating T. is defined by intensity of its secretion a thyroid gland and consumption of hormone on peripheries and it is controlled by thyritropic hormone (see), to-ry it is formed in a hypophysis (see. Triple hormones of a hypophysis ). Number of T. it is regulated by the principle of a feed-back (see) hormones of a thyroid gland. TSB are in blood in a condition of labile equilibrium with free T., to-ry can diffuse in fabric.
Free T., contained in blood in insignificant quantity, nevertheless defines a thyroid condition of an organism (hypo - hyper - or an euthyroidism), causes peripheral effect of hormone, speed of his metabolism (the period biol is normal. semi-lives of T. it is equal to 6 — 7 days) and influence on hypophysis (see).
A number of transformations of T is known., the most important of to-rykh is formed as a result of its monodeiodinating in situation 5' and is 3,5,3' - the triiodothyronine (T3) possessing fiziol. activity by 5 — 10 times of higher, than fiziol. T. V activity to a cell can occur monodeiodinating of T. in situation 5 with education ot3, not having hormonal activity. This process is considered as a way of elimination of excess amount of thyroxine from a metabolism. In other ways of a catabolism of thyroxine are its konjyu-girovaniye with beta and glucuronic and sulfuric to-tami, deamination (see) or transamination (see) rest of alanine of a side chain of its molecule. With urine or with a stake in not changed look only a small amount of thyroid hormones is excreted.
Active participation in metabolism of T. accepts a liver, in a cut the most part of T3 is formed. To deiodinating in a liver about 75% metaboliziruyemy are exposed to T., at the same time about 35% of T3 and 40% ot3 are formed. The ratio between the number of T3 and ot3 changes at nek-ry fiziol. and patol. states.
For hormones of a thyroid gland target organs are not established and still there is no standard theory explaining their hormonal influence at molecular level. The former popular concept connected action of T. with dissociation under its influence of tissue respiration and oxidizing fosfori-lirovan I, leading to decrease in accumulation of energy in the form of high-energy phosphatic bonds of vysokoergichesky connections (see). The raised oxygen absorption is typical for a thyrotoxicosis (see) — patol. the state caused by excess of thyroid hormones in blood, however, as showed new researches thyroid stimulation of oxidizing phosphorylation in mitochondrions was interfaced to tissue respiration, except for cases of a heavy thyrotoxicosis. According to a new hypothesis, T., obviously, in the beginning stimulates energy-requiring system, napr, active transmembrane transfer of ions of Na + (see Membranes biological), for the Crimea increase in oxygen absorption fabrics, strengthening of synthesis of protein necessary for formation of mitochondrions, and then filling by their enzymes follows. In 60 — the 70th 20 century the look, according to Krom action of T was approved. on cellular processes it is caused by stimulation of synthesis of protein in a cell. T. strengthens synthesis of respiratory enzymes in fabrics (see. Respiratory enzymes ), it is especially distinct — synthesis mitochondrial alpha glitserofosfatdegidrogenazy. Further researches confirmed action of T. on separate stages of synthesis of protein both at a stage of a transcription (see), and at a stage of broadcasting (see). Also binding sites of thyroid hormones on kernels of cells are established, receptor volume to-rykh correlates with sensitivity of fabric to effect of thyroxine. Thus, it is possible to assume that T. is the regulator of a metabolism in all sensitive to T. fabrics and probably this action is carried out by accession of hormone to a cellular kernel with initial influence on activity of a DNA-dependent RNA polymerase (see. Polymerases ) and subsequent increase in intensity of synthesis of protein. Similar, but not permanent effect of T. can render on mitochondrions.
There are more and more messages on influence of thyroid hormones on activity of adenylatecyclase (KF 188.8.131.52) and intracellular contents cyclic 3', 5' - AMF. Activation of adenilattsiklazny system by thyroid hormones in sensitive to T is established. fabrics (in a liver, kidneys, heart, fatty tissue and skeletal muscles) and lack of such effect in fabrics, insensitive to thyroxine (a spleen, a brain and lungs), both at introduction by his animal, and at addition to culture of fabrics.
Content of the proteinaceous and connected iodine (see) and butanolekstragiruyemy iodine (see) in blood testifies to total quantity of T. (see. Iodic exchange). Broad use for assessment of content of thyroid hormones in blood and others biol. substrates received so-called radioligandny methods, to-rye allow to define specifically T, T3 and other naturally found iodated components. One of these methods — a radio immunological method (see) — allows to define concentration of T4 in blood serum with a fine precision by special standard sets.
Maintenance of T. in blood normal makes 4 — 11 mkg / 10 0 ml (according to other data, 7 — 10 mkg / 100 ml). The quantity it is increased at a diffusion toxic craw (see. Craw diffusion toxic ), various diseases which are followed by a thyrotoxicosis it is also lowered at a hypothyroidism (see).
Small amount of T. it is extracted with urine. T. it is found also in breast milk. Its concentration in the first days of a lactation makes 0,6 — 1,5 mkg! 100 ml it is also rather low in comparison with the content of hormone in blood serum of mother, but gradually to 3 — from 7,3 to 12,9 mkg rise 4th week! 100 ml.
T. is a part of the pharmaceuticals used for replacement therapy at hypofunction of a thyroid gland — Thyreoidinum (see), the synthetic combined drugs, napr, Thyreocombum made in GDR, etc.
Bibliography: The guide to clinical endocrinology, under the editorship of V. G. Baranov, page 352, L., 1977; Thyroid hormones, under the editorship of. I. X. Turakulova, Tashkent, 1972; Endocrinology, ed. by L. J. De Groot a. o., v i N. Y. a. o., 1979; Hormones in blood, ed. ’by of Page H. Gray a. V. H. T. James, v i, L. — N. Y., 1979.
I. X. Turakulov.