Regulation of Progesterone-Metabolizing Enzyme by Adrenergic Agents, Prolactin, and Prostaglandins in Cultured Rat Ovarian Granulosa Cells*

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Abstract
The direct modulation of 20α-hydroxysteroid dehydrogenase (20α-OH-SDH) by regulatory agents of luteal functions was examined using in vitro cultures of ovarian granulose cells from immature, hypophysectomized, estrogen-treated rats. Without FSH priming, treatment with isoproterenol, PRL, or prostaglandin F2α (PGF2α) resulted in minimal modulation of the 20α-OH-SDH activity of granulosa cells. In contrast, after in vitro FSH priming, these hormones or agents caused marked changes in 20α-OH-SDH activity. Isoproterenol treatment inhibited 20α-OH-SDH activity in a dose-dependent manner (ED50, 3.4 × 10-10 M; maximal inhibition, 62% decrease). Similar inhibition of 20α-OH-SDH activity was observed after treatment with epinephrine, norepinephrine, and a β2-adrenergic agonist (terbutalino sulfate), whereas a β1 -adrenergic agonist (dobutamine) was less effective. Furthermore, the inhibitory effect of epinephrine was blocked by concomitant treatment with a β2- antagonist (IPS 339) but not by a β1-antagonist (practolol). In FSH-primed granulosa cells, treatment with ovine PRL inhibited 20α-OH-SDH activity in a dose-dependent manner (ED50, 33 Ng/ml; maximal inhibition, 90% decrease). Similar inhibition was observed in cells treated with human GH, whereas ovine GH was less effective. In contrast, treatment with PGF2α, but not PGA1 and PGA2, stimulated 20α-OH-SDH activity in a dosedependent fashion (170% increase at 10 mu;g/ml PGF2α). Moreover, concomitant treatment with PGF2α blocked the inhibitory effects of isoproterenol and PRL. Since FSH-primed granulosa cells respond to various regulatory agents of luteal functions in modulating 20a-OH-SDH activity, the present in vitro system provides a useful model for the study of the differentiation of granulosa cells to luteal cells. The luteotrophic effects of PRL and adrenergic agents are associated with decreases in 20α-OHSDH activity and are probably mediated through ovarian lactogenic and β2-adrenergic receptors, respectively. In contrast, the action of PGF2α is associated with an increase in 20α-OHSDH activity.