Dexamethasone Inhibits Transforming Growth Factor-(beta) Receptor (T(beta)R) Messenger RNA Expression in Hamster Preantral Follicles: Possible Association with NF-YA

To evaluate the site(s) and mechanism(s) of glucocorticoid-inhibition of transforming growth factor (TGF) (beta) receptor (T(beta)R) mRNA expression in ovarian cells, steady-state levels of T(beta)R mRNA in hamster preantral follicles exposed to FSH or estradiol with or without dexamethasone were determined by reverse transcription polymerase chain reaction and Southern hybridization. The effect of dexamethasone on follicular DNA and steroid synthesis and the expression of NF-Y and Sp3 were also investigated. Dexamethasone differentially inhibited FSH- or estradiol-induced expression of T(beta)R mRNA in preantral follicles at all stages. Dexamethasone also strongly inhibited FSH-induced but not TGF(beta)2-induced follicular DNA synthesis, and the inhibition was completely reversed by TGF(beta)2. However, TGF(beta)2 markedly attenuated FSH + dexamethasone-stimulated progesterone and FSH-induced follicular estradiol synthesis. Both FSH and estradiol upregulated NF-YA expression, but the effect was significantly attenuated by dexamethasone. Our results suggest that suppression of NFYA levels is one of the mechanisms whereby dexamethasone reduces hormone-induced T(beta)RI and T(beta)RII mRNA levels in hamster preantral follicles. Dexamethasone potentiates the effect of FSH on granulosa cell steroidogenesis, whereas TGF(beta) counteracts the effect. These data indicate that glucocorticoid and TGF(beta) may form an important regulatory loop to modulate FSH regulation of preantral follicular growth and differentiation.