Transforming growth factor beta inhibits steroidogenic acute regulatory (StAR) protein expression in human ovarian thecal cells.
In this study, we investigated the effects of TGFbeta1 on steroidogensis and expression of the steroidogenic acute regulatory (StAR) protein which regulates an important early step in the steroidogenic pathway. We utilized a human ovarian thecal like tumor (HOTT) cell model and investigated the effects of activin-A, inhibin-A, or TGFbeta1 in the presence of forskolin and the effect of dibutyryl cyclic AMP (dbcAMP) on steroid accumulation in the culture medium. Cells were also treated with different concentration of TGFbeta1 in the presence of forskolin, combined steroid production was measured at the end of 48 h and after 3 h incubation with 22R-hydroxycholesterol. In the presence of TGFbeta1 there was a dose-dependent inhibition of androstenedione production. Inhibition in combined steroid production was apparent at the highest concentration of TGFbeta1 tested. In the presence of 22R-hydroxycholesterol, combined steroid production was significantly inhibited at lower concentrations. TGFbeta1 inhibited StAR protein expression in a concentration dependent manner. There was also a similar inhibition in StAR mRNA. These results suggest that the effect of TGFbeta1 on steroid production and possibly follicular development may be in part due to its effects on StAR expression.
Attia
G R
GR
Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology, University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Blvd, Dallas, TX 75390, USA.
Dooley
C A
CA
Rainey
W E
WE
Carr
B R
BR
D000735:Androstenedione / Q000096:biosynthesis; D018929:Cell Culture Techniques / Q000379:methods; D005576:Colforsin / Q000494:pharmacology; D005260:Female; D006801:Humans; D015151:Immunoblotting; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000473:pathology; D010750:Phosphoproteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D011374:Progesterone / Q000096:biosynthesis; D020033:Protein Isoforms / Q000494:pharmacology; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D013799:Theca Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects; D000098682:Steroidogenic Acute Regulatory Protein
D009363:Neoplasm Proteins; D010750:Phosphoproteins; D020033:Protein Isoforms; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D000098682:Steroidogenic Acute Regulatory Protein; D005576:Colforsin; D000735:Androstenedione; D011374:Progesterone