Ovary

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

Abstract

To evaluate the site(s) and mechanism(s) of glucocorticoid-inhibition of transforming growth factor-b receptor [TR] mRNA expression in ovarian cells, steady-state levels of TR mRNA in hamster preantral follicles exposed to FSH or estradiol with or without dexamethasone were determined by RT-PCR and Southern hybridization. The effect of dexamethasone on follicular DNA and steroid synthesis, and expression of NF-Y and Sp3 was also investigated. Dexamethasone differentially inhibited FSH- or estradiol-induced expression of TR mRNA in preantral follicles at all stages. Further, dexamethasone strongly inhibited FSH-induced, but not TGF-2-induced follicular DNA synthesis, and the inhibition was completely reversed by TGF-2. On the other hand, TGF-2 markedly attenuated FSH+ dexamethasone-stimulated progesterone and FSH-induced follicular estradiol synthesis. Both FSH and estradiol up regulated NF-YA expression, but the effect was significantly attenuated by dexamethasone. Our results suggest that suppression of NF-YA levels is one of the mechanisms whereby dexamethasone reduces hormone-induced TRI and TbRII mRNA levels in hamster preantral follicles. Whereas dexamethasone potentiates the effect of FSH on granulosa cell steroidogenesis, TGF- counteracts the effect. Collectively, these data indicate that glucocorticoid and TGF- may form an important regulatory loop to modulate FSH-regulation of preantral follicular growth and differentiation.