Stimulation of beta 2-adrenergic responsiveness by follicle-stimulating hormone in rat granulosa cells in vitro and in vivo

The development of adrenergic responsiveness in ovarian granulosa cells cultured in the presence of androstenedione was investigated. Progesterone production by granulosa cells obtained from immature hypophysectomized diethylstilbestrol-treated rats was stimulated by FSH, but was only minimally affected by various adrenergic agents. In contrast, FSH treatment for 2 days in vivo or in vitro resulted in an increase in the adrenergic responsiveness of granulosa cells. Subsequent treatment with (-)epinephrine, (-)norepinephrine, or (-)isoproterenol (a potent beta-adrenergic agonist) resulted in time- and dose-dependent increases in progesterone production. The adrenergic agents enhanced the effects of hCG and PRL with respect to progesterone production, but were without effect on estrogen production or the maintenance of LH/hCG receptors in FSH-primed granulosa cells. A selective beta 2-adrenergic agonist (terbutaline) stimulated progesterone production in FSH-treated granulosa cells, whereas a beta 1-agonist (dobutamine) was 10,000-fold less effective. Furthermore, progesterone production induced by (-)epinephrine was blocked by a selective beta 2-antagonist (IPS 339), but the beta 1-antagonist (practolol) was 7,000-fold less effective. These results suggest that FSH treatment in vivo and in vitro increases beta 2-adrenergic responsiveness in ovarian granulosa cells and that this functional responsiveness is coupled to progesterone, but not to estrogen, biosynthesis.