Expression of 11 beta-hydroxysteroid dehydrogenase, glucocorticoid receptor, and mineralocorticoid receptor genes in rat ovary

A new concept in reproductive endocrinology is that the status of the ovary as a glucocorticoid target organ alters with follicular development. Evide nce for a physiological role of glucocorticoids in the regulation of ovaria n folliculogenesis has been strengthened by the discovery that 11 beta-hydr oxysteroid dehydrogenase (11 beta HSD) mRNA expression in human granulosa c ells is developmentally regulated. In this study, we quantified the pattern of expression and investigated the cellular location of 11 beta HSD type 1 (11 beta HSD1), 11 beta HSD type 2 (11 beta HSD2), glucocorticoid receptor (CR), and mineralocorticoid receptor (MR) mRNAs during follicular maturati on in rat ovary. immature female rats received treatment with eCG to induce preovulatory follicular development or eCG followed by hCG to induce lutei nization. 11 beta HSD1, 11 beta HSD2, GR, and MR mRNAs were all detectable by ribonuclease protection assay in ovarian total RNA. Treatment with eCG a lone caused an similar to 8-fold increase in the ovarian level of 11 beta H SD1 mRNA, which rose to similar to 30-fold after additional treatment with hCG. Equine CC alone did not measurably affect the ovarian 11 beta HSD2 mRN A level, but additional treatment with hCG reduced it to 34% of the control level. Expression of GR mRNA was unchanged by any gonadotropin treatment, while MR mRNA was down-regulated. A similar pattern of 11 beta HSD1, 11 bet a HSD2, GR, and MR mRNA expression was observed in isolated granulosa cells . These results provide direct experimental evidence that 11 beta HSD genes are gonadotropically regulated in the rat ovary, including granulosa cells , and are consistent with a shift in glucocorticoid metabolism from inactiv ation (due to oxidation by 11 beta HSD2) to activation (reduction by 11 bet a HSD1) during hCG-induced granulosa cell luteinization.