Adrenal Contribution to Polycystic Ovary Syndrome

Abstract

Objective: To examine further the dynamics of adrenal steroidogenesis in selected groups of patients with polycystic ovary syndrome (PCOS) compared to normal ovulatory women of the same age. Materials and Methods: Serum cortisol, testosterone, dehydroepiandrosterone sulphate (DHEAS), androstenedione (A), luteinizing hormone (LH), follicle-stimulating hormone, prolactin, 17-hydroxyprogesterone (17-OHP) and sex hormone-binding globulin (SHBG) were measured in the early follicular phase of the period. In addition, 2-day dexamethasone suppression and short adrenotropic hormone (ACTH) stimulation tests were performed for the study group and controls. Results: Serum testosterone (4.3 ± 1.8 nmol/l), LH (7.6 ± 1.9 IU/l), and 17-OHP (4.7 ± 2.3 nmol/l) were higher while SHBG (24.7 ± 14.2 nmol/l) was lower in patients than the control. Testosterone was significantly suppressed after dexamethasone suppression test while the level of 17-OHP increased significantly in patients more than the control after 60 min of ACTH stimulation. In the PCOS, the ratio of 17-OHP/A showed a significant increase after ACTH stimulation while that of DHEAS/A decreased when compared to controls. Conclusion: The study suggests a contribution of adrenal cytochrome P-450C dysregulation in PCOS. This suggestion could lead to another method of treating some PCOS patients when the usual anti-androgens might not be fully effective in controlling most of the symptoms.

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

“…In fact, P450c17α dysregulation has been attributed to the modulatory effects of cytochrome b5, insulin, and estradiol (13,23). In the current study, estradiol levels were not increased in the hyperandrogenic group, and this finding does not support previous observations indicating that estrogen may increase 17,20 lyase activity in the conversion of 17-OHP4 to A in PCOS patients (13,14). Although hyperandrogenic patients presented higher baseline insulin levels, reports of the role of insulin in P450c17α enzyme activity have been inconsistent (13,23,25).…”

“…Compared to healthy individuals, greater activity of 17,20 lyase was previously demonstrated in PCOS patients when they were diagnosed according to the Rotterdam criteria and taken as the only population group (14). On the other hand, 17-hydroxylase activity was shown to be the same in both PCOS and healthy women (14). There is currently no clear explanation for this inconsistency, but it is possible that 17-hydroxylase activity may be maximally driven, precluding its further increase in the conversion of P4 to 17-OHP4.…”

“…No consistent corticosteroidogenic enzyme abnormality has been reported in PCOS patients. After the introduction of the NIH/Rotterdam criteria in the clinical setting, only a few studies have examined the activities of these enzymes (14), so this was the principal goal of the current study. A detailed understanding the Δ4 and Δ5 corticosteroidogenic pathways is illustrated in figure 2 (9).…”

“…These observations are relevant because, in normal conditions, the human P450c17α enzyme possesses normal 17,20 lyase activity for the conversion of 17-OHPE to DHEA (Δ5 pathway) but minimal, if any, activity for the conversion of 17-OHP4 to A (Δ4 pathway) (26). Compared to healthy individuals, greater activity of 17,20 lyase was previously demonstrated in PCOS patients when they were diagnosed according to the Rotterdam criteria and taken as the only population group (14). On the other hand, 17-hydroxylase activity was shown to be the same in both PCOS and healthy women (14).…”

Comparison of steroidogenic pathways among normoandrogenic and hyperandrogenic polycystic ovary syndrome patients and normal cycling women

“…These observations are relevant because in healthy individuals, the human P450c17α enzyme possesses normal 17,20 lyase activity for the conversion of 17‐OHPE to DHEA (Δ5 pathway) but it has minimal, if any, activity for the conversion of 17‐OHP4 to A (Δ4 pathway) . Compared to healthy individuals, greater activity of 17,20 lyase was previously demonstrated in PCOS patients when they were taken as the only population group . However, the 17‐hydroxylase activity was shown to be equal in PCOS patients and healthy women .…”