Downregulation of the expression of inhibin α subunit and betaglycan in porcine cystic follicles
Betaglycan (TGFbeta type III receptor) was recently identified as a coreceptor to enhance the binding of inhibin A to activin type II receptor. This inhibin/betaglycan/activin type II receptor complex prevents activins from binding to their own receptors. The present study was undertaken to identify the expression and the regulation of the betaglycan gene in cultured rat granulosa cells. Northern blot analysis indicated betaglycan mRNA transcript of approximately 6.4 kbp. The treatment of the cells with FSH increased the betaglycan mRNA level, and a concurrent treatment with estradiol brought a significant increase in betaglycan mRNA. The protein kinase A activator, 8-bromoadenosine-cAMP, also increased the expression of its mRNA. Furthermore, betaglycan mRNA was induced additively by estradiol, which was blocked by estrogen receptor antagonists [ICI 182780, (R, R)-cis-diethyltetrahydro-2,8-chrysenediol]. In the luciferase assay, FSH altered the promoter activity of betaglycan. Moreover, when FSH plus estradiol was added to the granulosa cells, a significant increase in the half-life of betaglycan mRNA transcript was seen. In summary, FSH and estradiol increased betaglycan mRNA expression, most possibly through the protein kinase A pathway and the estrogen receptor-beta. The increase of betaglycan mRNA was due to an increase in transcription and altered mRNA stability. In ovarian regulatory function, the expression of betaglycan may involve the functional antagonism of inhibin A in activin signal transduction.