Indirect relationship between vasopressin-induced secretion of ACTH and cyclic nucleotides in cultured anterior pituitary cells.

The present study examines whether a correlation exists between cyclic nucleotides and the mechanism of action of arginine vasopressin (AVP) on adrenocorticotropin hormone (ACTH) secretion from pituitary corticotrophs. Incubation of cultured anterior pituitary cells with 3-isobutyl-1-methylxanthine (IBMX) or Rolipram elevated the basal intracellular content of both adenosine 3':5'-cyclic monophosphate (cAMP) and guanosine 3':5'-cyclic monophosphate (cGMP) or cAMP alone, respectively. Both IBMX and Rolipram enhanced the AVP-stimulated secretion of ACTH in cultured anterior pituitary cells, but not in AtT-20 corticotrophs which lack functional AVP receptors. Rolipram was less potent than IBMX in this regard, which suggests a possible involvement of cGMP. In contrast, both drugs showed similar potency to stimulate CRF-induced ACTH secretion. Incubation of pituitary cells with atrial natriuretic factor elevated tissue cGMP levels and increased the ACTH response to AVP. The results of this study show that, although AVP fails to directly affect the levels of cAMP and cGMP in anterior pituitary cells, the stimulatory effect of AVP on ACTH secretion was modulated by the cellular cAMP content.