Extrapituitary Functions of Thyrotropin-Releasing Hormone

Abstract

Thyrotropin-releasing hormone (TRH) was the first and smallest hypothalamic polypeptide to be isolated, purified, characterized, and synthesized (Vale and Rivier, 1975; Vale et al., 1977); its sequential tripeptide-amino acid structure is L-pyroglutamyl-L-histidyl-L-proline amide (pGlu-His-Pro-NH2). Synthetic TRH has been shown to stimulate in vivo and in vitro secretion of thyroid-stimulating hormones (TSH) from the adenohypophysis in all mammals (including humans). It effects prolactin (PRL) release as well (Brownstein, 1978; Vale and Rivier, 1975; Vale et al., 1977). Competitive radioreceptor TRH binding studies utilizing synthetic tritiated TRH ([3H]-TRH) in pituitary tissues (mouse thyrotropic and rat somatotropic/prolactotropic tumor, as well as normal bovine and rat membrane preparations) reveal high specificity of binding: [3H]-TRH binding is saturable; unlabeled TRH is capable of stoichiometric competition; and the majority of binding sites are localized in the plasma membrane subcellular fraction, which displays an approximate 40-fold increase in [3H]-TRH binding when compared with the total adenohypophyseal homogenate (Burt and Snyder, 1975; Burt and Taylor, 1980; Grant et al., 1973; Labrie et al., 1972, 1978; Poirier et al., 1972). In addition, a large number of synthetic TRH structural analogues have been synthesized and studied in the pituitary (Burt and Snyder, 1975; Burt and Taylor, 1980; Grant et al., 1973; Vale et al., 1973, 1977; Vale and Rivier, 1975; Vale, Rivier and Burgus, 1971). In general, the relative in vivo biological potency (percentage TSH release; percentage PRL release) of these analogues correlates fairly well with their in vitro radioreceptor [3H]-TRH competitive binding capabilities (relative affinities) in pituitary membrane receptors. Potent receptor antagonists, mainly TRH analogues, capable of blocking TRH-stimulated release of TSH have been synthesized (Bowers et al, 1976; Lybeck et al., 1973; Sievertsson et al., 1975).