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Transforming growth factor beta inhibits steroidogenic acute regulatory (StAR) protein expression in human ovarian
G R Attia1, C A Dooley, W E Rainey
1Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology, University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Blvd, Dallas, TX 75390, USA.
Abstract:
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.
Insights
Transforming growth factor beta1 (TGFbeta1) inhibits steroid production and steroidogenic acute regulatory (StAR) protein expression in human ovarian cells. This suggests TGFbeta1 may impact follicular development by affecting StAR expression.
Area of Science:
- Reproductive biology
- Endocrinology
- Cellular signaling
Background:
- Steroidogenesis is crucial for ovarian function and follicular development.
- The steroidogenic acute regulatory (StAR) protein is a key regulator of steroid hormone synthesis.
- Transforming growth factor beta1 (TGFbeta1) is implicated in various reproductive processes.
Purpose of the Study:
- To investigate the effects of TGFbeta1 on steroidogenesis in a human ovarian theca-like tumor (HOTT) cell model.
- To determine the impact of TGFbeta1 on the expression of the steroidogenic acute regulatory (StAR) protein and its mRNA.
- To elucidate the role of TGFbeta1 in regulating steroid production.
Main Methods:
- Utilized a human ovarian theca-like tumor (HOTT) cell model.
- Treated cells with TGFbeta1, forskolin, dibutyryl cyclic AMP (dbcAMP), and 22R-hydroxycholesterol.
- Measured androstenedione production, combined steroid production, StAR protein expression, and StAR mRNA levels.
Main Results:
- TGFbeta1 caused a dose-dependent inhibition of androstenedione production.
- Combined steroid production was inhibited by TGFbeta1, particularly at higher concentrations and with 22R-hydroxycholesterol.
- TGFbeta1 significantly suppressed both StAR protein and mRNA expression in a concentration-dependent manner.
Conclusions:
- TGFbeta1 inhibits steroid production in ovarian theca cells.
- TGFbeta1 exerts its inhibitory effects, at least partly, by downregulating StAR expression.
- These findings suggest TGFbeta1 may influence ovarian follicular development through modulation of StAR.