title: Dexamethasone inhibits transforming growth factor-beta receptor (Tbeta R) 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 (TGF) beta receptor (TbetaR) mRNA expression in ovarian cells, steady-state levels of TbetaR 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 TbetaR mRNA in preantral follicles at all stages. Dexamethasone also strongly inhibited FSH-induced but not TGFbeta2-induced follicular DNA synthesis, and the inhibition was completely reversed by TGFbeta2. However, TGFbeta2 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 TbetaRI and TbetaRII mRNA levels in hamster preantral follicles. Dexamethasone potentiates the effect of FSH on granulosa cell steroidogenesis, whereas TGFbeta counteracts the effect. These data indicate that glucocorticoid and TGFbeta may form an important regulatory loop to modulate FSH regulation of preantral follicular growth and differentiation.
authors.affiliation: Departments of Obstetrics, University of Nebraska Medical Center, Omaha, Nebraska 68198-4515, USA. skroy@unmc.edu
authors.forename: Shyamal K
authors.initials: SK
authors.lastname: Roy
authors.forename: Jinrong
authors.initials: J
authors.lastname: Wang
authors.forename: Peixin
authors.initials: P
authors.lastname: Yang
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D015153:Blotting, Western; D023081:CCAAT-Binding Factor / Q000378:metabolism*; D006224:Cricetinae; D004247:DNA / Q000096:biosynthesis / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D003907:Dexamethasone / Q000494:pharmacology*; D004958:Estradiol / Q000096:biosynthesis / Q000494:pharmacology; D005260:Female; D005455:Fluorescent Antibody Technique; D005640:Follicle Stimulating Hormone / Q000502:physiology; D008647:Mesocricetus; D006080:Ovarian Follicle / Q000187:drug effects / Q000378:metabolism*; D011247:Pregnancy; D011374:Progesterone / Q000096:biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis*; D018125:Receptors, Transforming Growth Factor beta / Q000096:biosynthesis*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012269:Ribosomal Proteins / Q000096:biosynthesis / Q000235:genetics; D051705:Sp3 Transcription Factor; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D000893:Anti-Inflammatory Agents; D023081:CCAAT-Binding Factor; D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D018125:Receptors, Transforming Growth Factor beta; D012269:Ribosomal Proteins; D014157:Transcription Factors; C402244:nuclear factor Y; C031798:ribosomal protein S4; D051705:Sp3 Transcription Factor; D011374:Progesterone; D004958:Estradiol; D003907:Dexamethasone; D005640:Follicle Stimulating Hormone; D004247:DNA