Transforming growth factor beta inhibits steroidogenic acute regulatory (StAR) protein expression in human ovarian thecal cells

In this study, we investigated the effects of TGF beta1 on steroidogensis a nd expression of the steroidogenic acute regulatory (StAR) protein which re gulates an important early step in the steroidogenic pathway. We utilized a human ovarian thecal like tumor (HOTT) cell model and investigated the eff ects of activin-A, inhibin-A, or TGF beta1 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 TG F beta1 in the presence of forskolin, combined steroid production was measu red at the end of 48 h and after 3 h incubation with 22R-hydroxycholesterol . In the presence of TGF beta1 there was a dose-dependent inhibition of and rostenedione production. Inhibition in combined steroid production was appa rent at the highest concentration of TGF beta1 tested. In the presence of 2 2R-hydroxycholesterol, combined steroid production was significantly inhibi ted at lower concentrations. TGF beta1 inhibited StAR protein expression in a concentration dependent manner. There was also a similar inhibition in S tAR mRNA. These results suggest that the effect of TGF beta1 on steroid pro duction and possibly follicular development may be in part due to its effec ts on StAR expression. (C) 2000 Elsevier Science Ireland Ltd. All rights re served.