Multiple factors involved in the control of ACTH and alpha-MSH secretion.

Alpha 1-adrenergic agents are potent stimulators of ACTH secretion directly at the pituitary level as observed using anterior pituitary cells in primary culture and by in vivo studies. On the other hand, beta-adrenergic as well as antidopaminergic agents are also potent stimulators of ACTH secretion but at a suprapituitary level, since no effect of these compounds are observed in vitro. CRF administration has been found to lead to rapid and parallel increases in ACTH and alpha-MSH concentrations in rat plasma and the mechanism of action of CRF has been studied in vitro using rat anterior and intermediate lobe of pituitary gland for ACTH and alpha-MSH secretion, respectively. In both cases, CRF stimulates adenylate cyclase activity at ED50 values of 70 and 350 nM for ACTH and alpha-MSH, respectively. CRF stimulates adenylate cyclase activity at least partly through a guanyl nucleotide-dependent mechanism. Using rat pars intermedia cells in culture, we have demonstrated the presence, in addition of a CRF receptor, of a beta 2-adrenergic receptor which stimulates cyclic AMP accumulation and alpha-MSH secretion and of a dopaminergic receptor which inhibits cellular activity. These results have been confirmed in in vivo studies where isoproterenol and thioproperazine (a dopamine antagonist) lead to a rapid increase of alpha-MSH secretion.