Thyroxine and T RH both act at the level of thyrotrophs of ant. pituitary where they antagonize each other

owever have challenged fhis idea. According fo some recenf works, fhyroxine causes increased Ca++ ATPase acfivity of myosin (which in turn may be due to increase in fhe bulk of myosin in heart muscle due to fhyroxine) increased contractility of myocardium. In short, excess thyroxine excess myosin in the myocardium increased contractility of the heart (ii) Central' nervous system. In the neonatal stage, up to the age of approximately 1 year, normal amount of thyroxine is required for the. satisfactory development of the nerve fibers and their myelination. If sufficient thyroxine is not available at this stage, the brain becomes small. The child grows in chronological age but his mental development does not occur. On the other hand, if fhyroxine becomes deficient after the full development of the CNS, some mental signs like mental slowing still develops but can be completely cured by thyroid administration. This is not so in the case of hypofhyroidism in the neonatals. If the hypothyroidism is not corrected within about 1 year of birth, no matter how vigoros is the subsequent treatment, satisfactory brain development will not occur. (iii) On skeletal system. Thyroxine is required for the growth and maturation of epiphyseal cartilage so that in the absence of this hormone, linear skeletal growth does not occur. Excess thyroxine causes osteoporosis because of calcium drainage from the bone (iv)On reproductive system. Lack of thyroxine in a dult woman of reproducing age. usually causes menorrhagia (= excessive menstrual bleeding) but the explanation is not definitely known. Hypofhyroidism may be associated with mfertility also. (v)0n digestive system. Excess thyroxine causes increased motility of the gastro intestinal tract (and thus causing diarrhea) and/or, increased appetite. Lack of fhyroxine causes reverse symptoms. (vi)On blood. In hypothyroidism a normocytic normochromic anemia is seen. MECHANISM OF ACTION As stated already (chap. i,-sec. VI, 'Mechanism of action. Thyroid hormones'), thyroid hormones act somewhat like the steroid hormones. The free (not' the TBG bound) T4 enters the target cell (almost all tissues are target cells of T4 , specially notable are the neurons, heart, liver, skeletal muscles, adipose tissues, mammary gland) converted into T3 HR (hormone receptor) complex is formed within, the nucleus HR attachment with DNA occurs more mRNA production synthesis of more proteins biological action. One single biochemical action of T4 (rather T3) at the molecular level cannot explain all the actions of thyroid hormones (TH). Thus, (i) as stated already (see above), the idea that TH causes 'uncoupling of oxidative phosphorylation' has been discarded, (ii) the idea, that, Na+ K+ ATPase enzyme is vigorosly synthesized so that TH causes calorigenesis, (although still very popular), does not explain all, (iii) TH causes increase in the synthesis of many proteins (including enzymes) which explains some of the effects of thyroxine (growth of neuron/rise in myocardial confractility/lung development in tad poles etc. etc. ) CONTROL OF THE THYROID SECRETION There are three major ways of controlling the thyroid secretion, viz, (i) the anterior pituitary, (ii) the hypothalmus, and (iii) autoregulation. Fig. 6.2.4 gives a diagramatic representation of the mode of working of the first two factors. Besides, some other factors like (iv) sympathetic stimulation (v) exposure to cold are also, important. Fig. 6.2.4. Control of Thyroid Secretion TSH of the anterior pituitary Some details have been discussed previously (in this chapter) in connection with the biosynthesis of the thyroid hormones. Additional details have been given in connection with the anterior pituitary hormones In short, thyroid simulating hormone, TSH, is secreted by the specialized cells, called thyrotrophs' of the anterior pituitary. (i) TSH stimulates almost all the major steps of fhyroxine biosynthesis as well as the release of thyroid hormones. Hence, more TSH = more secretion of thyroid. (2) In addition, it causes increased vascularity: and cellular growth of the thyroid gland. These are the two major actions of the TSH. TSH is controlled by negative feed back mechanism exerted by T4 and T3. The circulating T4 is converted into T3 at the level of the anferior pituitary and thus both T4 and T3 are active. Therefore, when circulating T4 is in high concentration, the pituitary thyrotroph is inhibited so that TSH secretion is depressed, resulting in correction of excess T4 in blood. Reverse occurs when T4 concentration of blood is low. Hence, more T4 =less TSH. TSH is the single most important regulator of the thyroid secretion. Hypothalamus From the hypothalamus, thyrofropin releasing hormone, TRH is secreted (NB. thyrotropin = TSH). TRH acts on pituitary thyrotrophs and stimulates them to secrete TSH. Hence more TRH = more TSH. Probably T4 and T3 do not operate at the level of the hypothalamus level for the feed back mechanism. Thyroxine and T RH both act at the level of thyrotrophs of ant. pituitary where they antagonize each other. Another hormones called somatostatin inhibits the TSH secretion. Somatostatin, in this, case, is released from fhe hypothalamus (somatostatin is also secreted by the islets of Langerhans and stomach). Autoregulation of thyroid If there is deficiency of the food iodine, the iodine trapping mechanism of the follicular cells become superefficient. Therefore, unless there is frank (severe) food iodine deficiency, supply of iodine to Ihe follicular cells, for synthesis of T4 and T3 continues satisfactorily. Conversely, if there is excess of the food iod