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

Abstract

Objective: To investigate whether the increased ovarian androgen synthesis in hyperthecosis is due to increased expression of the steroidogenic enzymes essential for androgen synthesis. Design: Controlled study to investigate concentration of steroidogenic enzymes 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 ovulatory cycles. Intervention(s): Ovarian stromal tissues were obtained from women with hyperthecosis and women with normal ovaries. Diagnosis of hyperthecosis was confirmed by histologic examination of the ovaries. Steroid levels were measured 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 Northern blot analysis using 32P-labeled complementary DNA (cDNA) probes encoding human P450 scc and P450 17α enzymes. Result(s): P450 scc and P450 17α messenger RNAs (mRNAs) were detected in the normal ovarian stroma and stromal hyperthecosis. Compared with normal ovarian stroma, P450 scc mRNA was increased twofold and P450 17α mRNA was increased threefold in stromal hyperthecosis. Conclusion(s): [1] Ovarian stroma is probably the site of androgen production in ovarian hyperthecosis. [2] Increased stromal androgen synthesis in hyperthecosis could be due to increased expression of the enzymes P450 scc and P450 17α in the ovarian stroma. [3] Markedly increased concentrations of 17α-hydroxyprogesterone in the ovarian vein serum indicate possible dysregulation of P450 17α in ovarian hyperthecosis.