The hypothalamic-pituitary-thyroid axis.

"TRH stimulates and somatostatin (SRIF) inhibits TSH release by acting directly on the thyrotroph. The negative-feedback loops (-), shown in red, inhibit TRH secretion and action on the thyrotroph, causing a decrease in TSH secretion. The feedback loops ( + ), shown in gray, stimulate somatostatin secretion, causing a decrease in TRH secretion. SRIF, somato-statin, or somatotropin release inhibiting factor.

lease. The thyroid hormones also increase the release of so-matostatin from the hypothalamus. Somatostatin (SRIF) inhibits the release of TSH from the thyrotroph (see Fig. 32.9). In the pituitary, thyroid hormones reduce the sensitivity of the thyrotroph to TRH and inhibit TSH synthesis.

The negative-feedback effects of the thyroid hormones on thyrotrophs are produced primarily through the actions of T3. Both T4 and T3 circulate in the blood bound to plasma proteins, with only a small percentage (less than 1%) unbound or free (see Chapter 33). The free T4 and T3 molecules are taken up by thyrotrophs, and T4 is converted to T3 by the enzymatic removal of one iodine atom. The newly formed T3 molecules and those taken up directly from the blood enter the nucleus, where they bind to thyroid hormone receptors in the chromatin. The interaction of T3 with its receptors changes the expression of specific genes in the thyrotroph, which decreases the cell's ability to produce and secrete TSH. For example, T3 inhibits the expression of the genes for the a and P subunits of TSH, directly decreasing the synthesis of TSH. Also, T3 influences the expression of other unidentified genes that code for proteins that decrease thyrotroph sensitivity to TRH. The loss in sensitivity is thought to be partly due to a reduction in the number of TRH receptors in thyrotroph plasma membranes.

Other Factors Affecting TSH Secretion. The exposure of certain animals to a cold environment stimulates TSH secretion. This makes sense from a physiological perspective because the thyroid hormones are important in regulating body heat production (see Chapter 33). Brief exposure of experimental animals to a cold environment stimulates the secretion of TSH, presumably a result of enhanced TRH se cretion. Newborn humans behave much the same way, in that they respond to brief cold exposure with an increase in TSH secretion. This response to cold does not occur in adult humans.

The hypothalamic-pituitary-thyroid axis, like the hypo-thalamic-pituitary-adrenal axis, follows a diurnal circadian rhythm in humans. Peak TSH secretion occurs in the early morning and a low point is reached in the evening. Physical and emotional stress can alter TSH secretion but the effects of stress on the hypothalamic-pituitary-thyroid axis are not as pronounced as on the hypothalamic-pituitary-adrenal axis.

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Essentials of Human Physiology

Essentials of Human Physiology

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