Abstract
Intracellular effector systems which utilize PKA and PKC can be pharmacologically activated by forskolin and phorbol 12-myristate 13-acetate (PMA) and appear to be important for regulation of Steroidogenesis by cells of the corpus luteum. In this study the effect of pharmacologic activation of PKA (forskolin) or PKC (PMA) on the activity of adenylate cyclase, cholesterol esterase, P450 cholesterol side chain cleavage (P450scc) and 3β-hydroxysteroid dehydrogenase/ Δ5,Δ4 isomerase (3βHSD) was determined. Basal adenylate cyclase activity (as measured by intracellular and secreted cAMP) was extremely low in both large and small luteal cells. Forskolin stimulated adenylate cyclase activity in both large and small luteal cells but progesterone production was increased only in small cells. PMA inhibited progesterone production by large and forskolin-stimulated small cells without altering adenylate cyclase activity. Basal cholesterol esterase activity was greater in small than in large cells and was stimulated by forskolin only in small cells. PMA did not significantly alter cholesterol esterase activity in either cell type. Activity of P450scc or 3βHSD was measured by conversion of hydroxylated cholesterol derivatives (P450scc) or pregnenolone (3β HSD) to progesterone. Although basal progesterone production was 47 times greater in large than small cells, there was only 5.1 (P450scc) and 6.4 (3βHSD) times greater enzyme activity in large than in small luteal cells. Activation of PKA and/or PKC did not alter the activity of P450scc or 3βHSD in either cell type. In conclusion, it appears that the difference in basal progesterone production between the small and large cells cannot be completely explained by differences in adenylate cyclase, cholesterol esterase, P450scc or 3βHSD enzyme activity. In addition we found that the only Steroidogenic enzyme acutely regulated by PKA or PKC was cholesterol esterase which was stimulated by PKA in small cells.
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