TSH is controlled by negative feed back mechanism eierted by T4 and T3.

owever have challenged this idea. According to some recent works. thyroxine causes increased Ca++ ATPase activity of myosin (which in turn may be due to increase in the bulk of myosin in heart muscle due to thyroxine) 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 slags, up to the age of approximately 1 year, normal amount of thyroxine is required for the satisfactory development of the neive fibers and their myelination. If sufficient thyronine is not available at this stage. the bram becomes small. The child grows in chronological age but his mental development does not occur. On the other hand, if thymune becomes deficient after the full development of the CNS, some mental signs like mental stowing still develops but can be completely cured by thyroid administration. This is not so in the case of hypolhyroidism in the neonatals If the hypolhyroidism 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. ThyroHine 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 thrioxnine causes osleopoiosis because of calcium drainage from the bone (iv)On reproductive system Lack ofthyromne in adult woman of reproducing age usually causes menorrhagia (= excessive menstrual bleeding) but the explanation is not definitely known HypoIhyioidism may be associated with infertility also. (v)0n digestive system. Excess thyrocxine causes increased motitrty of the gastrc intestinal trad (and thus causing diarrhea) and/or, increased appelite. Lack of thyroxine causes reverse symptoms. (vi)0n blood In hypothyroidism a normoeytic normochromic anemia is seen MECHANISM OF ACTION As stated already (chap i, ssc 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 DMA occurs more mRNA production synthesis of more proteins biological action One single biochemical action of T4 (rather T3) at Ihe molecular level cannot explain all the actions of thyroid hormones (TH) Thus, (i) as stated already (see above), trie idea that TM causes 'uncoupling of oxidative phasphorylaiion' has bsen discarded, (ii)the idea, that. Na+K+ ATPase enzyme is vigorosly synthesized so that TH causes calori genesis, (although still very popular), does not explain all. (iii) TH causes mcreass in the synthesis of many proteins (including enzymes) which explains some of The effects of thyroxine (growth ol neuron/rise in myocaidial contractilily/lung development in tadpoles etc etc ) CONTROL OF THE THYROID SECRETION There are three major ways of controlling [he ihyroid secretion, viz. (i) Tha anterior pituitary, (ii) the hypolhalmus, and (lii) auloregulation 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 Conlrol of Thyroid Secretion. TSH of the anterior pituitary Some details have been discussed previously (in this chapter) in connection with the biosynthesis of Ihe thyroid hormones. Additional details have been given in connection with the antenor pituitary hormones. In short, thyroid stimulating hormone, TSH. is secreted by Ihe specialized cells, tailed thyrotrophs' of the antenor pituitary, (i) TSH stimulates almost all the major steps of Thyromne biosynthesis as well as the release of thyroid hormones Hence, more TSH = more secretion of thyroid. (2) in addition, it causes increased vascuiarity and cellular growth of the thyroid gfarrd. These are the two major actions of the TSH. TSH is controlled by negative feed back mechanism eierted by T4 and T3. The circulating T4 is converted into T3 at the level of the anterior pituitary and thus both T4 and TB are active. Therefore, when Circulating T4 is in high concentration. the pituitary Ihyrolroph 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 ef the thyroid secretion Hypothalamus From the hypolhalamus, thyrotropin releasing hormone. TRH is secreted (NB. Ihyrotropin = TSH). TRH acts on pituilary thyrc-trophs and stimulates them to secrele TSH Hence more TRH = more TSH Probably T4 and T3 do not operate at the level of the hypolhalamus level for the feed back mechanism Thyioxine and TRH both act at the level of thyrotrophs of ant pituitary where they antagonize each other. Another hormones called somatostatin inhibits the TSH secielion. Somatostatin, in this case, is released from the hypothalamus [somatoslatin is also secreted by the islets of Langerhans and slornach) Autoremulation of thyroid If there is deficiency of the food iodine, The iodine trapping mechanism of The follicular cells become super efficient. Therefore, unless there is frank (severe] food iodine deficiency, supply of iodine to the follicular cells, for synthesis of T4 and T3 continues satisfactorily Conversely, if there is evcess of the food rod