Further Studies on the Mechanisms Controlling Prostaglandin Biosynthesis in the Cat Adrenal Cortex: The Role of Calcium and Cyclic AMP

Abstract

In light of previous studies which have implicated prostaglandin (PG) formation as a link in ACTH-induced steroid production by isolated cat adrenocortical cells, experiments were carried out to provide additional information regarding the role of PG in adrenal steroidogenesis and their interactions with Ca and cyclic[c]AMP. Perfusion of cat adrenal glands with Locke''s solution plus .beta.(1-24)-ACTH immediately increased PGF2.alpha. release, which rapidly declined to basal levels after the stimulus was withdrawn. Maximal rates of steroid release were manifest some 30 min after removal of ACTH. ACTH and its o-nitrophenyl sulfenyl derivative (NPS-ACTH) increased PG (PGF2.alpha. and PGE2) and steroid release by trypsin-dispersed cat cortical cells, but NPS-ACTH, unlike ACTH, did not augment cortical cAMP levels. In this same preparation, indomethacin completely blocked ACTH and NPS-ACTH facilitated PGF2.alpha. and PGE2 release but failed to suppress steroid release markedly. Ca- deprivation blocked PG and steroid release evoked by these 2 polypeptides, and depressed PG release elicited by monobutyryl cAMP (bcAMP) without affecting steroid release. The concept that PG play a role in the mode of action of ACTH was supported; however, they do not appear to be obligatory intermediates in the steroidogenic process. The importance of Ca in regulating PG formation is discussed with special regard for the idea that this cation has a direct action on the enzyme systems which control PG synthesis.