Regulation of vasopressin V-1b receptors in the anterior pituitary gland of the rat

Vasopressin secreted by parvocellular neurones of the hypothalamic paravent ricular nucleus modulates pituitary adrenocorticotrophic hormone (ACTH) sec retion by acting upon vasopressin V-1b type receptors in the pituitary cort icotroph coupled to phospholipase C. Regulation of V-1b receptors contribut es to the adaptation of the hypothalamic-pituitary-adrenal (HPA) axis to st ress, as evidenced by the correlation between vasopressin receptor number a nd pituitary ACTH responsiveness. V-1b receptor upregulation during chronic stress is associated with elevated circulating glucocorticoids and vasopre ssin expression in parvocellular neurones, suggesting that these factors co ntrol V-1b receptor expression. Removal of circulating glucocorticoids by a drenalectomy causes sustained vasopressin receptor downregulation, but redu ces V-1b receptor mRNA only transiently. The latter effect is not mediated by increased corticotrophin-releasing hormone (CRH) and vasopressin release , since it is not prevented by lesions of the hypothalamic paraventricular nucleus. Adrenalectomy causes sustained V-1b receptor loss in Brattleboro r ats, which lack hypothalamic vasopressin, suggesting that vasopressin media tes V-1b receptor mRNA recovery. Exogenous glucocorticoid administration do wnregulates pituitary vasopressin binding but increases V-1b receptor mRNA and facilitates coupling of the receptor to phospholipase C, effects which may contribute to the refractoriness of vasopressin actions to glucocortico id feedback. The lack of parallelism between changes in pituitary vasopress in binding and V-1b receptor mRNA levels during manipulation of the HPA axi s indicates that V-1b receptor content depends on post-transcriptional mech anisms rather than steady-state V-1b receptor mRNA levels. These studies su ggest that interaction between glucocorticoids and vasopressin plays an imp ortant role in regulating V-1b receptor mRNA expression during alterations of the HPA axis. In addition, the recent characterization of a major part o f the V-1b receptor gene provides a basis for studying the molecular mechan isms regulating the V-1b receptor.