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

• Published in: Molecular and cellular endocrinology 2000-12, Vol.170 (1), p.123-129
• Main Authors: Attia, George R, Dooley, Christina A, Rainey, William E, Carr, Bruce R
• Format: Article
• Language: English
• Subjects: Androstenedione - biosynthesis; Cell Culture Techniques - methods; Colforsin - pharmacology; Female; Humans; Immunoblotting; Neoplasm Proteins - antagonists & inhibitors; Neoplasm Proteins - genetics; Neoplasm Proteins - metabolism; Ovarian Neoplasms - pathology; Phosphoproteins - antagonists & inhibitors; Phosphoproteins - genetics; Phosphoproteins - metabolism; Progesterone - biosynthesis; Protein Isoforms - pharmacology; RNA, Messenger - drug effects; RNA, Messenger - metabolism; StAR; TGFβ1; Theca Cells - drug effects; Theca Cells - metabolism; Theca Cells - pathology; Thecal cell; Transforming Growth Factor beta - pharmacology; Tumor Cells, Cultured - drug effects
• ISSN: 0303-7207; 1872-8057
• DOI: 10.1016/S0303-7207(00)00335-X

In this study, we investigated the effects of TGFβ1 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 TGFβ1 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 TGFβ1 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 TGFβ1 there was a dose-dependent inhibition of androstenedione production. Inhibition in combined steroid production was apparent at the highest concentration of TGFβ1 tested. In the presence of 22R-hydroxycholesterol, combined steroid production was significantly inhibited at lower concentrations. TGFβ1 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 TGFβ1 on steroid production and possibly follicular development may be in part due to its effects on StAR expression.