ТИРЕОИДНЫЕ ГОРМОНЫ [ thyroid hormones ] Тиреоидные гормоны, или тиронины - это гормоны щитовидной железы. В соответствии с разным эмбриогенезом, химической структурой и назначением гормоны щитовидной железы разделяют на две группы. Одна группа - семейство йодаминокислотных гормонов, главными среди которых являются трийодтиронин, тетрайодтиронин (тироксин). Вторая группа - семейство пептидных гормонов кальцитонинов.
Йодаминокислотные гормоны щитовидной железы: 3,5,3'-трийодтиронин (Т3) и 3,5,3'5'-тетрайодтиронин (Т4, тироксин), являются главным средством нейрогуморального управления метаболизмом, развитием и дифференцированием тканей организма. Кальцитонин является средством управления гомеостазом кальция в организме.
Схема. Структура тиреоидных гормонов = Structures of thyroid hormones. Модификация: Jameson J., Ed. Harrison's Endocrinology, 2nd ed., McGraw-Hill, 2010, 560 p., см.: Физиология человека: Литература. Иллюстрации.
|
 |
Примечание:
|
Thyroxine (T4) contains four iodine atoms. Deiodination leads to production of the potent hormone triiodothyronine (T3), or the inactive hormone
reverse T3. 63 (63) |
|
Схема. Метаболизм иода = Iodine metabolism. Модификация: Gardner D.G., Shoback D.M., Eds. Greenspan's Basic & Clinical Endocrinology. 9th ed., Lange, 2011, 960 p., см.: Физиология человека: Литература. Иллюстрации.
|
 |
Примечание:
|
. The values indicated are representative of those that might be found in a healthy subject ingesting 500 g of iodine a day. The actual iodine intake varies considerably among different individuals. p. 7 |
|
Схема. Транспорт иода в щитовидной железе и синтез тиреоидных гормонов = thyroid iodine transport and thyroid hormone synthesis. Модификация: Melmed S., Polonsky K.S., Larsen P.R., Kronenberg H.M., Eds. Williams Textbook of Endocrinology, 12th ed., Saunders, 2011, 1816 p., см.: Физиология человека: Литература. Иллюстрации.
|
 |
Примечание:
|
Schematic illustration of a follicular cell showing the key aspects of thyroid iodine transport and thyroid hormone synthesis. AC, Adenyl cyclase;
ATPase, adenosine triphosphatase; cAMP, cyclic adenosine monophosphate; D1, thyroidal deiodinase type 1; D2, thyroidal deiodinase type 2; DAG, diacylglycerol;
DEHAL1, iodotyrosine dehalogenase 1 (IYD); DIT, diiodotyrosine; DUOX, dual oxidase; IP3, inositol triphosphate; MIT, monoiodotyrosine; NADP+, oxidized
form of nicotinamide adenosine dinucleotide phosphate; NADPH, reduced nicotinamide adenosine dinucleotide phosphate; NIS, sodium-iodide symporter;
PDS, pendrin (SLC26A4); PLC, phospholipase C; T3, triiodothyronine; T4, thyroxine; Tg, thyroglobulin; TPO, thyroid peroxidase TSHR, thyrotropin receptor. 335 (329) |
|
|
Схема. Распределение свободных активных тиреоидных гормонов в организме = Representation of free T4 (and free T3) as the biologically active hormones at the level of the pituitary and the peripheral tissues. Модификация: Gardner D.G., Shoback D.M., Eds. Greenspan's Basic & Clinical Endocrinology. 9th ed., Lange, 2011, 960 p., см.: Физиология человека: Литература. Иллюстрации.
Примечание:
Representation of free T4 (and free T3) as the biologically active hormones at the level of the pituitary and the peripheral tissues. Most of the thyroid hormones circulating in plasma are protein-bound and have no biologic activity. This pool of bound hormone is in equilibrium with the free hormone pool. |
 |
|
|
Примечание:
Rates are expressed in nmol/24 h and are approximations based upon available data. 100 nmol of T4 is equivalent to approximately 75 g. (rT3, reverse T3; TETRAC, tetraiodothyroacetic acid.) |
 |
|
|
Примечание:
TRH produced in the hypothalamus reaches the thyrotrophs in the anterior pituitary by the hypothalamo-hypophysial portal system and stimulates the synthesis and release of TSH. In both the hypothalamus and the pituitary, it is primarily T3 that inhibits TRH and TSH secretion, respectively. T4 undergoes monodeiodination to T3 in neural and pituitary as well as in peripheral tissues. |
 |
|
Схема. Регулирование синтеза тиреоидных гормонов = Regulation of thyroid hormone synthesis. Модификация: Jameson J., Ed. Harrison's Endocrinology, 2nd ed., McGraw-Hill, 2010, 560 p., см.: Физиология человека: Литература. Иллюстрации.
|
 |
Примечание:
|
Left. Thyroid
hormones thyroxine (T4) and triiodothyronine (T3) feed back
to inhibit hypothalamic production of thyrotropin-releasing
hormone (TRH) and pituitary production of thyroid-stimulating
hormone (TSH). TSH stimulates thyroid gland production of T4
and T3.
Right. Thyroid follicles are formed by thyroid epithelial
cells surrounding proteinaceous colloid, which contains thyroglobulin.
Follicular cells, which are polarized, synthesize thyroglobulin
and carry out thyroid hormone biosynthesis (see
text for details). TSH-R, thyroid-stimulating hormone receptor;
Tg, thyroglobulin; NIS, sodium-iodide symporter; TPO, thyroid
peroxidase; DIT, diiodotyrosine; MIT, monoiodotyrosine. 64 (64) |
|
|
Примечание:
The thyroid
hormone receptor (TR) and retinoid X receptor (RXR)
form heterodimers that bind specifically to thyroid hormone
response elements (TREs) in the promoter regions of target
genes. In the absence of hormone, TR binds co-repressor
(CoR) proteins that silence gene expression. The numbers
refer to a series of ordered reactions that occur in response
to thyroid hormone: (1) thyroxine (T4) or triiodothyronine (T3)
enters the nucleus; (2) T3 binding dissociates CoR from TR;
(3) coactivators (CoA) are recruited to the T3-bound receptor;
(4) gene expression is altered. |
 |
|
Таблица. Стимуляция тиреотропином функций клеток щитовидной железы = Thyroid cell functions stimulated by thyrotropin. Модификация: Melmed S., Polonsky K.S., Larsen P.R., Kronenberg H.M., Eds. Williams Textbook of Endocrinology, 12th ed., Saunders, 2011, 1816 p., см.: Физиология человека: Литература. Иллюстрации. |
№ |
Function Affected |
General Mechanism |
I. МЕТАБОЛИЗМ ИОДА Iodide Metabolism |
1 |
Increase I- in follicular lumen |
PLC |
2 |
Delayed increased in NIS expression |
cAMP |
3 |
Increase thyroid blood flow |
↑ NO synthesis ( ↓ cellular
iodide) |
4 |
Increase in I- efflux from thyroid cell |
? |
II. СИНТЕЗ ТИРЕОИДНЫХ ГОРМОНОВ Thyroid Hormone Synthesis |
7 |
↑ Hydrogen peroxide |
PLC |
8 |
↑ Thyroglobulin and TPO synthesis |
cAMP |
9 |
↑ NADPH via pentose-phosphate pathway |
? |
III. СЕКРЕЦИЯ ТИРЕОИДНЫХ ГОРМОНОВ Thyroid Hormone Secretion |
10 |
↑ Pinocytosis of thyroglobulin |
cAMP |
11 |
↑ Release of thyroglobulin into plasma via the basolateral membrane |
cAMP (?) |
12 |
Mitogenesis |
cAMP; PLC; IGF1- and FGF-mediated kinase activation |
Примечание:
|
cAMP, cyclic adenosine monophosphate;
FGF, follicular growth factor;
IGF1-, insulin-like growth factor;
I-, plasma iodide; NADPH, reduced nicotinamide adenosine dinucleotide phosphate; |
S, sodium-iodide symporter;
NO, nitric oxide;
PLC, phospholipase C;
TPO, thyroid peroxidase. 339 (333)
|
|
Схема. Возможные пути поступления трииодтиронина в центральную нервную систему = Potential pathways for entry of triiodothyronine
(T3) into the central nervous system. Модификация: Melmed S., Polonsky K.S., Larsen P.R., Kronenberg H.M., Eds. Williams Textbook of Endocrinology, 12th ed., Saunders, 2011, 1816 p., см.: Физиология человека: Литература. Иллюстрации. |
 |
Thyroid hormones are
transported through the blood-brain barrier via the action of
an organic anion transporting polypeptide (OATP) or through
the blood-CSF barrier via OATP and monocarboxylate transporter
8 (MCT8). In the astrocytes and tanycytes, thyroxine
(T4) is converted to T3, which then enters the neurons, possibly
via MCT8. In the neurons, both T4 and T3 are degraded by type
3 deiodinase (D3). T3 from the tanycytes may reach the portal
vessels in the median eminence. Other transporters may be
present on the astrocyte or tanycyte membranes. In most
cases, transport could be bidirectional, although only one
direction is shown. CSF, cerebrospinal fluid; D2, type 2 iodothyronine
deiodinase; MCT10, monocarboxylate transporter
10; T2, diiodothyronine. 342 (346) |
|
Таблица. Сравнение трииодтиронина и тироксина = Comparison of Triiodothyronine (T3) and Thyroxine (T4) in Humans. Модификация: Melmed S., Polonsky K.S., Larsen P.R., Kronenberg H.M., Eds. Williams Textbook of Endocrinology, 12th ed., Saunders, 2011, 1816 p., см.: Физиология человека: Литература. Иллюстрации. |
№ |
Показатели |
Т3 |
Т4 |
1 |
Production rate (nmol/day) Fraction from thyroid |
50 0,2 |
110 1,0 |
2 |
Relative metabolic potency |
1,0 |
0,3 |
3 |
Serum concentration Total (nmol/L) Free (pmol/L) |
1.8 5 |
100 20 |
4 |
Fraction of total hormone in free form (Ч10-2) |
0,3 |
0,02 |
5 |
Distribution volume (L) |
40 |
10 |
6 |
Fraction intracellular |
0,64 |
0,15 |
7 |
Half-life (days) |
0,75 |
6,7 |
Примечание:
|
*To convert T4 from nmol/L to мg/dL (total) or from pmol/L to ng/dL (free),
divide by 12.87; to convert T3 from nmol/L to ng/dL (total) or from pmol/L
to pg/dL (free), multiply by 65.1. 344 (338)
|
|
Схема. Потоки кальция в тканях здорового организма в условиях минерального гомеостаза = Calcium fluxes in a normal individual in a state of zero external mineral balance. Модификация: Gardner D.G., Shoback D.M., Eds. Greenspan's Basic & Clinical Endocrinology. 9th ed., Lange, 2011, 960 p., см.: Физиология человека: Литература. Иллюстрации.
Примечание:
Calcium fluxes in a normal individual in a state of zero external mineral balance. The blue arrows denote unidirectional calcium fluxes; the pink arrows denote net fluxes. |
 |
|
Таблица. Внешние проявления действия тиреоидных гормонов в норме на различные органы-мишени = Physiologic Effects of Thyroid Hormones. Модификация: McPhee S. J., Hammer G.D., Eds. Pathophysiology of Disease: An Introduction to Clinical Medicine, 6th ed., McGraw-Hill, 2010, 752 p. см.: Физиология человека: Литература. Иллюстрации. |
№ |
Effect |
Mechanism |
I. СЕРДЦЕ Heart |
1 |
Хронотропный Chronotropic |
Увеличивают количество и чувствительность β-адренергических рецепторов Increase number and affinity of β-adrenergic receptors |
2 |
Inotropic |
Enhance responses to circulating catecholamines Increase proportion of alpha-myosin heavy chain (with higher ATPase activity) |
II. ЖИРОВАЯ ТКАНЬ Adipose tissue |
3 |
Catabolic |
Stimulate lipolysis |
III. МЫШЦЫ Muscle |
4 |
Catabolic |
Increase protein breakdown |
III. КОСТИ Bone |
5 |
Developmental and metabolic |
Promote normal growth and skeletal development; accelerate bone turnover |
IV. НЕРВНАЯ СИСТЕМА Nervous system |
6 |
Developmental |
Promote normal brain development |
V. ЖЕЛУДОЧНО-КИШЕЧНЫЙ ТРАКТ Gut |
7 |
Metabolic |
Increase rate of carbohydrate absorption |
VI. ЛИПОПРОТЕИНЫ Lipoprotein |
8 |
Metabolic |
Stimulate formation of LDL receptors |
VII. ТЕРМОРЕГУЛЯЦИЯ Thermoregulation |
9 |
Calorigenic |
Stimulate oxygen consumption by metabolically active tissues (exceptions: adult brain, testes, uterus, lymph nodes, spleen, anterior pituitary) |
VIII. МЕТАБОЛИЗМ Metabolism |
10 |
Calorigenic |
Increase metabolic rate |
Примечание:
|
Key: ATPase, adenosine triphosphatase; LDL, low-density lipoprotein.
Mechanism of Action of Thyroid Hormones.
Thyroid hormones enter cells by either passive diffusion or specific transport through the cell membrane and cytoplasm. Within the cell cytoplasm, most of the T4 is converted to T3. The nuclear receptor for T3 has been cloned and found to be similar to the nuclear receptors for glucocorticoids, mineralocorticoids, estrogens, progestins, vitamin D3, and retinoic acid. For reasons that are unclear, at least two different T3 receptors, coded by different genes, exist in human tissues. The two biologically active human thyroid hormone receptors (hTR) are labeled hTR-1 and hTR-1. The gene for the alpha form is on chromosome 17 and for the beta form on chromosome 3. The two different receptor forms may help to explain both the normal variation in thyroid hormone responsiveness of various organs and the selective tissue abnormalities found in various thyroid resistance syndromes. For example, the brain contains mostly receptors, the liver contains mostly receptors, and the heart contains both. Point mutations in the hTR-1 gene result in abnormal T3 receptors and the syndrome of generalized resistance to thyroid hormone (Refetoff's syndrome).
When the T3 receptor complex binds to DNA, it increases expression of specific genes, with the induction of messenger RNAs. A wide variety of enzymes must be produced to account for the many effects of thyroid hormones on cell function.
Effects of Thyroid Hormones.
Thyroid hormones increase the activity of membrane-bound Na+-K+ ATPase, increase heat production, and stimulate oxygen consumption (calorigenesis). Thyroid hormones also affect tissue growth and maturation, help regulate lipid metabolism, increase cardiac contractility by stimulating the expression of myosin protein, and increase intestinal absorption of carbohydrates. The effects of T4 and T3 and the catecholamines epinephrine and norepinephrine are closely interrelated. Both increase the metabolic rate and stimulate the nervous system and heart. In humans, the transcriptional effects of T3 include production of increased -adrenergic receptors; in animals, incubation of thyroid cells in a medium containing TSH increases the number of 1-adrenergic receptors, presumably by inducing their biosynthesis.
|
ЭНДОКРИНОЛОГИЯ: ОГЛАВЛЕНИЕ
ЭНДОКРИНОЛОГИЯ: ИЛЛЮСТРАЦИИ.
ЭНДОКРИНОЛОГИЯ: ТАБЛИЦЫ.
ЭНДОКРИНОЛОГИЯ: ЛИТЕРАТУРА.
«Я У Ч Е Н Ы Й И Л И . . . Н Е Д О У Ч К А ?» Т Е С Т В А Ш Е Г О И Н Т Е Л Л Е К Т А
Предпосылка: Эффективность развития любой отрасли знаний определяется степенью соответствия методологии познания - познаваемой сущности. Реальность: Живые структуры от биохимического и субклеточного уровня, до целого организма являются вероятностными структурами. Функции вероятностных структур являются вероятностными функциями. Необходимое условие: Эффективное исследование вероятностных структур и функций должно основываться на вероятностной методологии (Трифонов Е.В., 1978,..., ..., 2015, …).
Критерий: Степень развития морфологии, физиологии, психологии человека и медицины, объём индивидуальных и социальных знаний в этих областях определяется степенью использования вероятностной методологии.
Актуальные знания: В соответствии с предпосылкой, реальностью, необходимым условием и критерием...
... о ц е н и т е с а м о с т о я т е л ь н о: — с т е п е н ь р а з в и т и я с о в р е м е н н о й н а у к и, — о б ъ е м В а ш и х з н а н и й и — В а ш и н т е л л е к т !
|
♥ Ошибка? Щелкни здесь и исправь ее! Поиск на сайте E-mail автора (author): tryphonov@yandex.ru
|