New insights into steroidogenesis in normo- and hyperandrogenic polycystic ovary syndrome patients

Objective: This study sought to examine corticosteroidogenic enzyme activities in normo-and hyperandrogenic polycystic ovary syndrome (PCOS) patients. Subjects and methods: This cohort study included 81 patients with biochemical hyperandrogenism and 41 patients with normal androgen levels. Enzyme activities were assessed according to the serum steroid product/precursor ratios at baseline and after adrenal stimulation. Results: At baseline, in the delta 4 (Delta 4) pathway, hyperandrogenic patients showed greater 17-hydroxylase and 17,20 lyase activities in converting progesterone (P4) into 17-hydroxyprogesterone (17-OHP4) and 17-hydroxypregnenolone (17-OHPE) into androstenedione (A) (p = 0.0005 and p = 0.047, respectively) compared to normoandrogenic patients. In the delta 5 (Delta 5) pathway, the 17-hydroxylase and 17,20 lyase enzymes showed similar activities in both groups. Hyperandrogenic patients presented lower 21-hydroxylase, lower 11 beta-hydroxylase (p = 0.0001), and statistically significant increases in 3 beta-hydroxysteroid dehydrogenase II (3 beta-HSDII) activities (p < 0.0001). Following tetracosactrin stimulation, only the 17,20 lyase activity remained up-regulated in the Delta 4 pathway (p < 0.0001). Conclusion: Hyperandrogenic patients had higher 17,20 lyase activity, both at baseline and after adrenal stimulation. Greater conversion of dehydroepiandrosterone (DHEA) into A with normal conversion of 17-OHPE to 17-OHP4 in hyperandrogenic PCOS patients indicated different levels of 3 beta-HSDII activity in adrenal cells, and hyperandrogenic patients had lower 11 beta-hydroxylase and 21-hydroxylase activities.