Effect of follicle-stimulating hormone and estrogen on the expression of betaglycan messenger ribonucleic acid levels in cultured rat granulosa cells.
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.
Omori
Yuki
Y
Department of Obstetrics and Gynecology, School of Medicine, Gunma University, Gunma 371-8511, Japan.
Nakamura
Kazuto
K
Yamashita
Soichi
S
Matsuda
Hiroko
H
Mizutani
Tetsuya
T
Miyamoto
Kaoru
K
Minegishi
Takashi
T
D000818:Animals; D002478:Cells, Cultured; D054746:Cyclic AMP-Dependent Protein Kinase Type II; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004054:Diethylstilbestrol / Q000494:pharmacology*; D004958:Estradiol / Q000494:pharmacology*; D004967:Estrogens / Q000502:physiology*; D005260:Female; D005640:Follicle Stimulating Hormone / Q000494:pharmacology*; D005822:Genetic Vectors; D006107:Granulosa Cells / Q000187:drug effects / Q000502:physiology*; D011509:Proteoglycans / Q000235:genetics*; D018075:RNA, Complementary; D012333:RNA, Messenger / Q000235:genetics*; D051381:Rats; D011960:Receptors, Estrogen / Q000037:antagonists & inhibitors*; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics*; D014158:Transcription, Genetic / Q000187:drug effects; D014162:Transfection
D004967:Estrogens; D011509:Proteoglycans; D018075:RNA, Complementary; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D018125:Receptors, Transforming Growth Factor beta; C071736:betaglycan; D004958:Estradiol; D004054:Diethylstilbestrol; D005640:Follicle Stimulating Hormone; D054746:Cyclic AMP-Dependent Protein Kinase Type II; D017868:Cyclic AMP-Dependent Protein Kinases