The effect of kaurenol on steroidogenesis and cyclic adenosine monophosphate production in rat granulosa cells.

ABSTRACT

The effect of kaurenol (ent-kaur-16-en-15 beta-ol) on steroidogenesis and cyclic AMP production was examined in rat granulosa cells in short-term incubations (6 h). Kaurenol alone significantly augmented the production of progesterone in time- and concentration-dependent manner but attenuated the accumulation of the progesterone metabolite 20 alpha-hydroxypregn-4-en-3-one (20 alpha-OH-P). The steroidogenic effect of kaurenol is due to the acute stimulation of pregnenolone production from endogenous cholesterol and an inhibition in 20 alpha-hydroxysteroid dehydrogenase which catalyzes the metabolism of progesterone to 20 alpha-OH-P. Kaurenol had no appreciable effect on conversion of exogenous pregnenolone to progesterone. Although kaurenol was without effect on basal cyclic AMP generation, it inhibited the actions of luteinizing hormone (LH), follicle-stimulating hormone (FSH) and forskolin on the production of the cyclic nucleotide. Kaurenol also significantly attenuated the LH-, FSH- and forskolin-stimulated progesterone and 20 alpha-OH-P production in a concentration-dependent manner. Because kaurenol induced steroidogenesis without increased cyclic AMP accumulation, it is concluded that its action on basal steroidogenesis is mediated by a mechanism independent of the cyclic nucleotide. Kaurenol may serve as a useful tool for elucidating cyclic AMP-independent action(s) of hormones in intact tissue/cells.