Abstract

OBJECTIVE: Our purpose was to determine the effects of transforming growth factor-β on steroidogenesis and regulation of steroidogenic enzyme expression by use of a human ovarian thecal-like tumor cell culture system. STUDY DESIGN: Human ovarian thecal-like tumor cells were treated in serum-free medium in the presence or absence of forskolin and transforming growth factor-β 1 . The accumulation of progesterone and androstenedione in the culture medium was evaluated by radioimmunoassay. The effects of forskolin with or without transforming growth factor- β 1 on the enzymatic activity of P450c17 and 3 βHSD, the expression of immunodetectable P450c17 protein, and the expression of messenger ribonucleic acid for P450scc, P450c17, and 3 βHSD were determined. RESULTS: Basal steroid secretion, steroidogenic enzyme activity, enzyme protein, and messenger ribonucleic acid expression were not affected by transforming growth factor-β 1 alone. Forskolin treatment significantly stimulated steroid production and the enzymatic activity of P450c17 and 3 βHSD up to 10-fold above basal levels. However, transforming growth factor- β 1 inhibited forskolin-stimulated androstenedione production to near basal levels and increased progesterone 1.4- to 2-fold while suppressing P450c17 enzyme activity to near basal levels, but it did not affect 3 βHSD activity. Forskolin-stimulated immunodetectable P450c17 α protein was markedly inhibited by transforming growth factor- β 1 . In addition, transforming growth factor- β 1 markedly inhibited the forskolin-stimulation of P450c17 messenger ribonucleic acid, while not significantly altering P450scc or 3 βHSD messenger ribonucleic acid expression. CONCLUSION: Forskolin stimulated human ovarian thecal-like tumor cell steroidogenesis, P450c17 and 3βHSD activity, immunodetectable P450c17, and messenger ribonucleic acid content for P450scc, P450c17, and 3βHSD. Transforming growth factor-β 1 inhibited forskolin stimulation of androstenedione production through the inhibition of P450c17 expression. (A M J O BSTET G YNECOL 1996;174:1109-17.)

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