The thyrotrope secretes TSH in response to humoral signals (Fig. 15-2). The hypothalamic neurohormones TRH, somatostatin, and dopamine are released under control of the central nervous system. Thyroid hormones feed back to suppress TSH release. Other hormones, including corticosteroids and cytokines, also can modulate TSH secretion.

Physiologic alterations in TSH secretion in response to factors such as circadian rhythm, cold exposure (in neonates and lower animals), and stress are controlled by the central nervous system through pathways that project to hypothalamic nuclei to modulate hypothalamic releasing hormone secretion. Numerous neurotransmitters, including biogenic amines, amino acids, endogenous opioids, and neuropeptides, have been found to modulate TSH secretion in animals.20,21 For example, in rats, the TSH response to cold exposure appears to be mediated by α-adrenergic pathways.

TRH, a tripeptide (pyroglutamyl-histidyl-proline amide), was one of the first hypothalamic releasing hormones to be isolated and characterized (Fig. 15-3). The mammalian TRH prohormone contains multiple copies of the sequence Gln-His-Pro-Gly, suggesting that several TRH molecules could be derived from each precursor.22 The highest density of TRH-containing cells in the central nervous system is found in the hypothalamic paraventricular nucleus.23 TRH also is distributed extensively in the extrahypothalamic brain and in nonneuronal tissue, including the heart and testis.24 High-affinity TRH receptors are widely distributed; many behavioral, pharmacologic, and neurophysiologic effects have been reported after TRH administration. Hence, TRH may function as a neurotransmitter.21 However, probably only TRH released into the hypothalamic-pituitary portal circulation is involved in control of TSH secretion. Transcription of TRH is also under negative feedback regulation by T₃. TREs have been identified in the regulatory region of the TRH gene.24