A relationship between hyperactivity of the adrenal gland and inhibition of normal ovarian function has been proposed; however, the importance of direct glucocorticoid effects in determining the extent of follicle differentiation is unclear. In view of the critical role of an increase in granulosa cell LH/hCG receptor in the development of preovulatory follicles, we have examined direct glucocorticoid effects on the FSH induction of LH/hCG receptor in cultured granulosa cells. Further, we have correlated this action with two other important differentiative functions of granulosa cells, namely estrogen and progesterone production. Granulosa cells from immature hypophysectomized diethylstibestrol-treated rats were cultured in serum-free medium containing FSH in the presence or absence of dexamethasone. After 2 days of exposure to 10 ng/ml FSH, the granulosa cells exhibited a 12-fold increase in specific [125I] iodo-hCG binding (control, 0.7 ± 0.1; FSH-treated, 8.2 ± 0.6 fmol/106 cells). In contrast, exposure to a combination of FSH plus 1 μM dexamethasone resulted in a marked decrease in [125I] iodo-hCG binding (FSH- and dexamethasone-treated, 2.2 ± 0.3 fmol/106 cells). Scatchard analysis demonstrated that dexamethasone decreased the concentration of specific high affinity LH/ hCG-binding sites without influencing receptor affinity. The distribution of [125I]iodo-hCG binding, as determined by autoradiography, revealed a heterogeneity in granulosa cells with respect to the capacity to acquire LH/hCG receptor in response to FSH (only 56% of the granulosa cells acquired LH/hCG receptor) as well as the ability of granulosa cells to respond to glucocorticoids (dexamethasone did not fully suppress FSH induction of LH/hCG receptor). In addition to its effects on LH/ hCG receptor, dexamethasone also inhibited FSH-stimulated aromatase activity, but stimulated progesterone production. Each of these responses was dose dependent and was not attributable to a reduction in cell viability or number. Further, treatment with various corticoid hormones suggested that these responses were a function of the glucocorticoid rather than the mineralocorticoid potencies of the corticoid hormones administered. These observations raise the possibility that adrenal glucocorticoids may act directly on follicles to modulate FSHdependent granulosa cell differentiation and, thus, suggest that ovarian failure associated with adrenal hyperactivity can be explained, at least in part, by direct glucocorticoid actions in the ovary. (Endocrinology113: 1356, 1983)
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Schoonmaker et al. (1983) studied this question.