Effects of hormone treatment and age on the stimulation of rat anterior pituitary adenylate cyclase and cyclic adenosine 3',5' monophosphate by hypothalamic extract

Crude ovine hypothalamic extract in vitro significantly stimulated adenylate cyclase activity and LH release by pituitary gland obtained from newborn rats (0.25–0.5 days old) and increased cyclic adenosine 3′,5′-monophosphate (cyclic AMP) in 2-day-old rats. In adult rats, the stimulation of adenylate cyclase activity and cyclic AMP formation, but not LH release, induced by hypothalamic extract was inhibited by adrenalectomy. In vivo administration of pharmacologic doses of 1 mg dexamethasone asd 100 μg thyroxine for 1 day markedly reduced the effect of 0.2 mg/ml but not 1 mg/ml hypothalamic extract on cyclic AMP concentrations. The action of the latter dose of hypothalamic extract on cyclic AMP was inhibited by injection of dexamethasone and thyroxine for 3 days, while the stimulation of LH release was preserved. Such dissociation between activation of the adenylate cyclase-cyclic AMP system and LH release suggests that cyclic AMP formation may not be essential for increased release of LH. Adrenalectomy did not inhibit stimulation of adenylate cyclase activity or cyclic AMP formation caused by prostaglandin E₁ (PGE₁). Hypothalamic extract or PGE₁ added to intact pituitary in vitro increased protein kinase activity and decreased the protein binding of exogenous cyclic AMP, reflecting the increased generation of endogenous cyclic AMP.