REGULATION OF THYROTROPIN-RELEASING-HORMONE IN THE POSTERIOR PITUITARY

Although the presence of thyrotropin-releasing hormone (TRH) in the po sterior pituitary (PP) ws reported more than one decade ago, knowledge on its origin, regulation and functional significance is lacking. In the present study we investigated the regulation of TRH in the rat PP. Analysis by specific RIA, anion and cation exchange chromatography an d reverse-phase HPLC showed that all TRH immunoreactivity in the PP is accounted for by authentic TRH. Induction of hyperthyroidism with thy roxine increased levels of TRH in the PP by 20%, whereas in methimazol e-treated, hypothyroid rats the content decreased by 25% versus untrea ted, euthyroid controls. Food deprivation for 3 days increased levels by 35% and refeeding completely normalized TRH content again. Also 14- 17 days after castration, TRH in the PP was increased by 25% while tes tosterone substitution prevented this increase. Castration did not aff ect proTRH mRNA levels in the hypothalamus. One week after adrenalecto my or daily subcutaneous dexamethasone injections, TRH content in the PP was not affected. Treatment with disulfiram, an inhibitor of the pe ptidylglycine alpha-amidating monooxygenase (PAM), reduced levels of T RH in the PP by 20%. ProTRH and PAM mRNA levels were not affected in t he hypothalamus by this treatment. Since TRH in the PP has been sugges ted to play a role in prolactin (PRL) release, we determined the conte nt of TRH in the PP during a 6-hour suckling stimulus that increased P RL levels in peripheral blood 30-fold. Whereas TRH in the median emine nce increased by 35%, 6 h after the initiation of suckling, TRH levels in the PP remained constant. In conclusion, (1) authentic TRH account s for all TRH immunoreactivity in the PP, (2) TRH content in the PP is increased in conditions in which hypothalamic TRH release is reported ly decreased (hyperthyroidism, starvation, castration) and decreased w hen TRH release is increased (hypothyroidism) - its levels may thus be used as a parameter of TRH content in hypothalamic hypophysiotropic n eurons; (3) the changes in TRH levels in the PP in conditions that alt er thyroid-stimulating hormone (TSH) levels in peripheral plasma sugge st a role in TSH secretion, and (4) TRH in the PP does not seem to be important for the suckling-induced PRL release.