60 YEARS OF NEUROENDOCRINOLOGY: TRH, the first hypophysiotropic releasing hormone isolated: control of the pituitary–thyroid axis

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   Figure 1

   Time line. Figure depicts the principal discoveries that contributed to the actual understanding of TRH neurons and regulation of the hypothalamus–pituitary–thyroid axis (HPT). Above the blue line are marked some of the main findings in techniques or in cellular biology. Below are those related to the HPT axis. Space constraints makes it impossible to cite each piece of work, and some examples represent the ideas and paradigms of various authors. BMR, basal metabolic rate; IEGs, immediate early genes; ISH, in situ hybridization; KO, knock out; ME, median eminence; NGF, nerve growth factor; POMC, proopiomelanocortin; PVN, paraventricular nucleus; TH, thyroid hormones; TRF, thyrotropin-releasing factor.
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   Figure 2

   Elements involved in HPT regulation. At the level of the paraventricular hypothalamic nucleus (PVN), Trh mRNA is transcribed, its expression is regulated by multiple effectors, processed TRH is released from terminals localized at the median eminence (ME) in yuxtaposition with tanycytes that contain deiodinase 2 (D2) and pyroglutamyl peptidase II (PPII). In response to nutrient status, arcuate neurons synthesizing POMC/CART or NPY/AgRP project to the PVN and activate or inhibit (respectively) TRH neurons. Released TRH may be degraded by PPII before reaching portal vessels that transport it to the pituitary where it controls synthesis of TSHb and glycosylation of both TSH subunits (a and b) to form bioactive TSH. At the thyroid, TSH stimulates synthesis and release of T₄ that is modified at target tissues by deiodinases (e.g. D1 and D2).

• © 2015 Society for Endocrinology