The thyrotropin-releasing hormone gene: differential regulation, expression, and function in hypothalamus and two unexpected extrahypothalamic loci, the heart and testis.

Thyrotropin-releasing hormone (TRH) is the key regulator of the synthesis and secretion of TSH in animals and humans (Wilber and Yamada 1990). The biological implications of this peptide, the first releasing hormone to be characterized, has generated a large literature regarding both pituitary TSH and extrapituitary roles of TRH as a neurotransmitter and/or neuro-modulator in the central nervous system (O'Leary and O'Connor 1995, Morley 1981). In this review, new areas of TRH biology are explored, focused on the differential regulation of the TRH gene by triiodothyronine (T(3)) and other substances in the hypothalamus and two unexpected extrahypothalamic loci, the heart and testis. These new directions should enlarge our understanding concerning how hormones like T(3) regulate genes negatively and selectively with the identical receptors and DNA elements required for positive gene stimulation. In addition, regulatory studies of the TRH gene by T(3) should be relevant to other hormone receptor interactions with DNA sequences in general, as glucocorticoids, mineralocorticoids, sex steroids, vitamin D, and retinoic acid are ligands for homologous receptor proteins in the nuclear receptor superfamily.