THE EFFECT OF INSULIN AND INSULIN-LIKE GROWTH-FACTORS ON THE EXPRESSION OF STEROIDOGENIC ENZYMES IN A HUMAN OVARIAN THECAL-LIKE TUMOR-CELL MODEL

Objective: To determine the effects of insulin and insulin-like growth factors (IGF-I and IGF-II) on steroidogenesis and steroidogenic enzym e expression in a human ovarian thecal-like tumor cell culture model s ystem. Design: Human ovarian thecal-like tumor cells treated with fors kolin and insulin IGF-I or IGF-II were evaluated for media accumulatio n of P and androstenedione (A) as well as 3 beta-hydroxysteroid dehydr ogenase (3 beta HSD) and cytochrome P450 17 alpha-hydroxylase (P450c17 ) enzyme activity. Northern analysis of cytochrome P450 side chain cle avage (P450scc), P450c17, and 3 beta HSD messenger RNA (mRNA) also was performed. Results: Basal hormone secretion, enzyme activity, and mRN A levels were not affected by treatment with insulin or the IGFs. Fors kolin treatment stimulated steroid production, enzyme activity, and mR NA content. Forskolin-stimulated P secretion was augmented 30% by trea tment with insulin and IGFs, whereas 3 beta HSD activity was augmented twofold to threefold. Forskolin stimulated A and P450c17 activity wer e enhanced by treatment with insulin and the IGFs. In forskolin-treate d cells, P450c17 and P450scc mRNA levels were not affected by insulin (100 nhl) or IGF (10 nM) treatment; however, 3 beta HSD mRNA levels we re augmented by treatment with insulin and IGFs. Conclusions: We obser ved that forskolin-stimulated human ovarian thecal-like tumor cell ste roidogenesis, P450c17, and 3 beta HSD activity, as well as mRNA conten t for P450scc, 3 beta HSD, and P450c17. Insulin and the IGFs augmented forskolin-stimulated production of P and the expression of 3 beta HSD , with little effect on A production, P450scc, or P450c17 expression.