Angiotensin II interferes with steroidogenesis in porcine granulosa cells

The elements for the synthesis and activity of the vasopressor angiotensin II (AII) are present in the mammalian ovary. In the present investigation, the effects of AII were determined on three parameters of steroidogenic function in porcine granulosa cells in vitro: the accumulation of progesterone, the cellular content of the enzyme 3 beta-hydroxysteroid dehydrogenase delta 5-4 isomerase (3 beta-HSD), and the accumulation of mRNA for 3 beta-HSD. Cells were incubated with LH (200 ng/ml) in the presence or absence of AII (10(-7) M) or phorbol 12-myristate 13-acetate (PMA, 10(-7) M); doses of AII from 10(-10) to 10(-6) M in the presence or absence of LH; the AII reactor antagonist saralasin (10(-6) M) in the presence of AII or in combination of AII and LH; and AII in the presence or absence of (Bu)2 cAMP. The results demonstrate that LH increased progesterone, 3 beta-HSD message, and 3 beta-HSD content. Both PMA and AII interfered with the LH-induced progesterone accumulation, reducing the response by 50% or more. All also abrogated the LH-induced increases in 3 beta-HSD mRNA and 3 beta-HSD enzyme content in porcine granulosa cells. The AII inhibition was dose-dependent. The AII receptor antagonist saralasin blocked the inhibitory effects of AII on LH-induced steroidogenic events. AII interfered with the (Bu)2 cAMP induction of steroidogenesis and 3 beta-HSD mRNA and enzyme accumulation when (Bu)2 cAMP was present at a concentration of 30 microM.(ABSTRACT TRUNCATED AT 250 WORDS)