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Dexamethasone Inhibits Transforming Growth Factor-ß Receptor (TßR) Messenger RNA Expression in Hamster Preantral Follicles: Possible Association with NF-YA¹

Departments of Obstetrics and Gynecology and Physiology and Biophysics, University of Nebraska Medical Center, Omaha, Nebraska 68198-4515

To evaluate the site(s) and mechanism(s) of glucocorticoid-inhibition of transforming growth factor (TGF) ß receptor (TßR) mRNA expression in ovarian cells, steady-state levels of TßR 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 TßR mRNA in preantral follicles at all stages. Dexamethasone also strongly inhibited FSH-induced but not TGFß2-induced follicular DNA synthesis, and the inhibition was completely reversed by TGFß2. However, TGFß2 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 NF-YA levels is one of the mechanisms whereby dexamethasone reduces hormone-induced TßRI and TßRII mRNA levels in hamster preantral follicles. Dexamethasone potentiates the effect of FSH on granulosa cell steroidogenesis, whereas TGFß counteracts the effect. These data indicate that glucocorticoid and TGFß may form an important regulatory loop to modulate FSH regulation of preantral follicular growth and differentiation.

¹ This study was supported by research grants HD 28165 and HD 38468 from the National Institute of Child Health and Human Development, NIH.

² Correspondence: Shyamal K. Roy, Departments of Obstetrics and Gynecology and Physiology and Biophysics, BH 4030, University of Nebraska Medical Center, 984515 Nebraska Medical Center, Omaha, NE 68198-4515. FAX: 402 559 6164; skroy{at}unmc.edu

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