The effect of insulin and insulin-like growth factors on the expression of steroidogenic enzymes in a human ovarian thecal-like tumor cell model

To determine the effects of insulin and insulin-like growth factors (IGF-I and IGF-II) on steroidogenesis and steroidogenic enzyme expression in a human ovarian thecal-like tumor cell culture model system. Human ovarian thecal-like tumor cells treated with forskolin and insulin IGF-I or IGF-II were evaluated for media accumulation of P and androstenedione (A) as well as 3β-hydroxysteroid dehydrogenase (3βHSD) and cytochrome P450 17α-hydroxylase (P450c17) enzyme activity. Northern analysis of cytochrome P450 side chain cleavage (P450scc), P450c17, and 3βHSD messenger RNA (mRNA) also was performed. Basal hormone secretion, enzyme activity, and mRNA levels were not affected by treatment with insulin or the IGFs. Forskolin treatment stimulated steroid production, enzyme activity, and mRNA content. Forskolin-stimulated P secretion was augmented 30% by treatment with insulin and IGFs, whereas 3βHSD activity was augmented twofold to threefold. Forskolin stimulated A and P450c17 activity were enhanced by treatment with insulin and the IGFs. In forskolin-treated cells, P450c17 and P450scc mRNA levels were not affected by insulin (100 nM) or IGF (10 nM) treatment; however, 3βHSD mRNA levels were augmented by treatment with insulin and IGFs. We observed that forskolin-stimulated human ovarian thecal-like tumor cell steroidogenesis, P450c17, and 3βHSD activity, as well as mRNA content for P450scc, 3βHSD, and P450c17. Insulin and the IGFs augmented forskolin-stimulated production of P and the expression of 3βHSD, with little effect on A production, P450scc, or P450c17 expression.