Angiotensin II- and phorbol ester-induced steroidogenesis by ovine adrenocortical cells: effect of sex and the gonadal status of the donor animal.

Abstract

1. Angiotensin II (AngII) is well recognized as a regulator of adrenal cortisol production in the sheep in vivo, but studies to date have failed to reveal this action on cultured ovine adrenocortical cells. Similarly, phorbol myristate acetate (PMA), an activator of protein kinase C, also has little effect on cortisol production from ovine adrenocortical cells in vitro. Previous studies have, however, only looked at the responses to single concentrations of AngII or PMA, but have led to the suggestion that important differences exist between adrenocortical 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 AngII (10(-10) to 10(-6) mol/L) or PMA (10(-10) to 10(-5) mol/L). In addition, we have investigated the possible role of gonadal factors in regulating these responses by comparing cultures derived from intact and gonadectomized male and female sheep. 3. Angiotensin II caused concentration-dependent increases (P < 0.05) in cortisol production in all cultures, with cortisol production in response to AngII being greater (P < 0.05) in cultures from intact male sheep than in the cultures from orchidectomized males or intact females. Cortisol production in response to AngII was modest in all groups (two- to 2.6-fold increases). 4. Phorbol 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 < 0.05) of cortisol production in cultures from intact male sheep than either the orchidectomized males or intact females. 5. These findings demonstrate that ovine adrenocortical cells are responsive in a concentration-dependent fashion to AngII and PMA. In addition, sex and gonadal factors may play an important role in regulating the responsiveness of adrenocortical cells to these factors.