Regulation of Progestin Biosynthetic Enzymes in Cultured Rat Granulosa Cells: Effects of Prolactin, β 2-Adrenergic Agonist, Human Chorionic Gonadotropin and Gonadotropin Releasing Hormone 1

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Abstract
Prolactin (Prl), .beta.2-adrenergic agents and human chorionic gonadotropin (hCG) are luteotropic in rats, while gonadotropin releasing hormone (GnRH) exerts direct inhibitory effects on ovarian steroidogenesis. The modulation of the progestin biosynthetic pathway by the luteotropic agents as well as the actions of GnRH was examined. Rat granulosa cells were primed with FSH to increase their responsiveness to the luteotropic agents. Subsequent treatment for 2 days with Prl, terbutaline (a .beta.2-adrenergic agonist) or hCG stimulated the production of progesterone, 20.alpha.-hydroxypregn-4-en-3-one (20.alpha.-OH-P), pregnenolone and the activity of 3.beta.-hydroxysteroid dehydrogenase (3.beta.-HSD). In contrast, treatment with Prl or terbutaline but not hCG, inhibited 20.alpha.-hydroxysteroid dehydrogenase (20.alpha.-HSD) activity by decreasing the apparent maximal velocity of the enzyme with no change in its Km value. Concomitant treatment with GnRH inhibited progesterone, but increased 20.alpha.-OH-P production stimulated by Prl or terbutaline. These effects were associated with a stimulation of 20.alpha.-HSD activity, while neither 3.beta.-HSD activity nor pregnenolone biosynthesis was decreased.In contrast, GnRH inhibited progesterone production in hCG-treated cells without affecting 20.alpha.-OH-P production. This was associated with an inhibitory effect of GnRH on pregnenolone biosynthesis with no effect upon 3.beta.-HSD activity. Prl and the .beta.2-agonist stimulate progesterone production and 3.beta.-HSD activity. The inhibitory effect of GnRH on Prl- or terbutaline-stimulated progesterone production appears to result from a preferential increase in 20.alpha.-HSD activity, while the GnRH inhibition of hCG-stimulated progesterone production appears to result from a preferential inhibition of pregnenolone production.