ANGIOTENSIN-II-INDUCED AND PHORBOL ESTER-INDUCED STEROIDOGENESIS BY OVINE ADRENOCORTICAL-CELLS - EFFECT OF SEX AND THE GONADAL STATUS OF THE DONOR ANIMAL

1. Angiotensin II (AngII) is well recognized as a regulator of adrenal cortisol production in the sheep in vivo, but studies to date have fa iled to reveal this action on cultured ovine adrenocortical cells, Sim ilarly, phorbol myristate acetate (PMA), an activator of protein kinas e C, also has little effect on cortisol production from ovine adrenoco rtical cells in vitro. Previous studies have, however, only looked at the responses to single concentrations of AngII or PMA, but have led t o the suggestion that important differences exist between adrenocortic al cells of the sheep and other species. 2. We have extended previous studies by examining cortisol production by ovine adrenocortical cells over 3 h in response to a broad range of concentrations of either Ang II (10(-10) to 10(-6) mol/L) or PMA (10(-10) to 10-5 mol/L), In additi on, we have investigated the possible role of gonadal factors in regul ating these responses by comparing cultures derived from intact and go nadectomized male and female sheep. 3. Angiotensin II caused concentra tion-dependent increases (P<0.05) in cortisol production in ail cultur es, with cortisol production in response to AngII being greater (P<0.0 5) in cultures from intact male sheep than in the cultures from orchid ectomized males or intact females. Cortisol production in response to AngII was modest in all groups (two- to 2.6-fold increases). 4. Phorbo l myristate acetate elicited a concentration-dependent inhibition (P<0 .01) of basal cortisol production in adrenocortical cultures from all groups, Phorbol myristate acetate produced a greater inhibition (P<0.0 5) of cortisol production in cultures from intact male sheep than eith er the orchidectomized males or intact females. 5. These findings demo nstrate that ovine adrenocortical cells are responsive in a concentrat ion-dependent fashion to AngII and PMA. In addition, sex and gonadal f actors may play an important role in regulating the responsiveness of adrenocortical cells to these factors.