Increased expression of messenger ribonucleic acid encoding cytochrome P450 cholesterol side-chain cleavage and P450 17 alpha-hydroxylase enzymes in ovarian hyperthecosis

Objective: To investigate whether the increased ovarian androgen synthesis in hyperthecosis is due to increased expression of the steroidogenic enzyme s essential for androgen synthesis. Design: Controlled study to investigate concentration of steroidogenic enzy mes in the ovarian stroma of women with hyperthecosis of the ovaries. Setting: Academic research environment. Patient(s): Three women with ovarian hyperthecosis and eight with normal ov ulatory cycles. Intervention(s): Ovarian stromal tissues were obtained from women with hype rthecosis and women with normal ovaries. Diagnosis of hyperthecosis was con firmed by histologic examination of the ovaries. Steroid levels were measur ed in the ovarian vein serum of one patient with hyperthecosis, Main Outcome Measure(s): Tissues were frozen immediately in liquid nitrogen and kept frozen until RNA was extracted. Total RNA was examined by Norther n blot analysis using P-32-labeled complementary DNA (cDNA) probes encoding human P450(scc) and P450(17 alpha) enzymes. Result(s): P450(scc) and P450(17 alpha) messenger RNAs (mRNAs) were detecte d in the normal ovarian stroma and stromal hyperthecosis. Compared with nor mal ovarian stroma. P450(scc) mRNA was increased twofold and P450(17 alpha) mRNA was increased threefold in stromal hyperthecosis. Conclusion(s): [1] Ovarian stroma is probably the site of androgen producti on in ovarian hyperthecosis. [2] Increased stromal androgen synthesis in hy perthecosis could be due to increased expression of the enzymes P450(scc) a nd P450(17 alpha) in the ovarian stroma, [3] Markedly increased concentrati ons of 17 alpha-hydroxyprogesterone in the ovarian vein serum indicate poss ible dysregulation of P450(17 alpha) in ovarian hyperthecosis. (Fertil Ster il(R) 1999,71:328-33. (C) 1999 by American Society for Reproductive Medicin e.)