Human Biochemistry, Volume 2 - Murray R. 1993

Biochemistry of Intracellular and Intercellular Communication
Thyroid Hormones
Regulation of Synthesis and Release of Thyroid Hormones

The main components that make up the negative feedback loop are T4, T3, thyrotropin, and thyroliberin (Fig. 46.4). T4 and T3 inhibit their own synthesis via a feedback mechanism. T3 may act as the mediator of this process, since T4 is converted to T3 in the Pituitary Gland. At this level, feedback inhibits thyrotropin release. T3 (or possibly T4) can suppress both the release and production of thyroliberin by the Hypothalamus. The stimulus for increased secretion of thyroliberin and thyrotropin is a drop in the Blood levels of THYROID Hormones. However, even with a complete blockade of thyroid hormone Biosynthesis (e.g., during antithyroid drug therapy), there is no immediate surge in thyroliberin and thyrotropin release. The Thyroid Gland contains a reserve of previously synthesized hormone sufficient to maintain supply for several weeks; There are also extrathyroidal hormone reserves (in The Liver and bound to TBG) that are depleted first. Furthermore, if hormone biosynthesis is threatened by iodine deficiency, an autoregulatory mechanism of the thyroid gland plays an additional compensatory role.

There is an intriguing interplay between the negative feedback loops of the thyroid gland and Growth Hormone, driving The regulatory mechanisms shown in Fig. 46.4. T3 and T4 enhance the release of Somatostatin from the hypothalamus, and this peptide in turn inhibits thyrotropin secretion by the pituitary gland. Somatostatin is also involved in another mechanism: its levels rise in response to increased plasma levels of Insulin-like growth factor 1 (IGF-1), which is stimulated by growth hormone (see Chapter 45 and Fig. 45.5). Short-stature children receiving growth hormone therapy occasionally develop hypothyroidism, apparently due to elevated IGF-1 concentrations that drive up somatostatin secretion, which consequently leads to a drop in thyrotropin secretion.

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Fig. 46.4. Feedback Regulation of Thyroid hormone biosynthesis. Solid lines with ⊕ symbols indicate stimulatory pathways, while dashed lines with ⊝ symbols indicate inhibitory pathways. IGF — insulin-like growth factor; SS — somatostatin; TRH — thyrotropin-releasing hormone (thyroliberin); TSH — thyroid-stimulating hormone.



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