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

Abstract

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 (Δ4) 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 (Δ5) pathway, the 17-hydroxylase and 17,20 lyase enzymes showed similar activities in both groups. Hyperandrogenic patients presented lower 21-hydroxylase, lower 11β-hydroxylase (p = 0.0001), and statistically significant increases in 3β-hydroxysteroid dehydrogenase II (3β-HSDII) activities (p < 0.0001). Following tetracosactrin stimulation, only the 17,20 lyase activity remained up--regulated in the Δ4 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 3β-HSDII activity in adrenal cells, and hyperandrogenic patients had lower 11β-hydroxylase and 21-hydroxylase activities. Arq Bras Endocrinol Metab. 2013;57(6):437-44 Keywords Polycystic ovary syndrome; steroidogenesis; hyperandrogenism; enzyme activity; adrenal stimulation RESUMO Objetivo: O objetivo deste estudo foi examinar a atividade de enzimas responsáveis pela produção de corticosteroides em pacientes normo e hiperandrogênicas com síndrome de ovários policísticos (SOP). Sujeitos e métodos: A coorte estudada incluiu 81 pacientes com hiperandrogenismo bioquímico e 41 pacientes com níveis normais de androgênio. A atividade enzimática foi avaliada de acordo com as proporções de produto/precursor do esteroide sérico, no momento inicial do estudo e depois de estimulação adrenal. Resultados: No momento inicial, na via delta 4 (Δ4), as pacientes hiperandrogênicas mostraram maior atividade da 17-hidroxilase e 17,20 liase na conversão da progesterona (P4) em 17-hidroxiprogesterona (17-OHP4) e na conversão da 17-hidroxipregnenolona (17-OHPE) em androstenediona (A) (p = 0,0005 e p = 0,047, respectivamente) em comparação com pacientes normoandrogênicas. Na via delta 5 (Δ5), a 17-hidroxilase e a 17,20 liase mostraram atividades similares nos dois grupos. As pacientes hiperandrogênicas mostraram menor atividade da 21-hidroxilase, menor atividade da 11β-hidroxilase (p = 0,0001) e aumento estatisticamente significativo na atividade da 3β-hidroxiesteroide desidrogenase II (3β-HSDII) (p < 0.0001). Após a estimulação com tetracosactrin, apenas a ativi...

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

“…The 17‐hydroxylase enzyme promotes rapid conversion of pregnenolone (PE) and progesterone (P4) into 17‐hydroxypregnenolone (17‐OHPE) and 17‐hydroxyprogesterone (17‐OHP4), respectively; in tandem, and more slowly, the 17,20 lyase enzyme converts 17‐OHPE and 17‐OHP4 into dehydroepiandrosterone (DHEA) and androstenedione (A), respectively. Two additional adrenal enzymes are involved: 3β‐hydroxysteroid dehydrogenase II (3β‐HSDII) drives precursors towards the synthesis of P4, 17‐OHP4 and A; and sulfotransferase (SULT2A1) which transforms DHEA into DHEA sulfate (DHEA‐S) …”

Prevalence of Elevated Glycated Hemoglobin Concentrations in the Polycystic Ovary Syndrome: Anthropometrical and Metabolic Relationship in Amazonian Women

“…The sample size was estimated using an imprecision (i) value of 5%, a mean expected effect of 14% (based on scarce previous studies reporting on the proportion of PCOS patients with an elevated HbA1c) and an alpha level of 5% [10, 14, 15]. Written informed consent was obtained from each patient, as approved by the local Committee for Ethics in Research.…”

“…Patients were excluded for any of the following reasons: use of sex steroids or insulin-sensitizing drugs over the previous 6 months; thyroxin-stimulating hormone (TSH) concentration ≥ 4.2 µUI/mL and prolactin (PRL) concentration > 25 ng/mL (1,086 nmol/L). Non-classic 21-hydroxylase, 11β-hydroxylase and 3β-hydroxysteroid dehydrogenase (3β-HSD) were excluded as published elsewhere [15]. …”

“…PCOS diagnosis was performed according to the National Institutes of Health and Rotterdam criteria [1, 15]. Clinical hyperandrogenism was defined as a dichotomous variable using the presence or not of hirsutism in the following body areas: upper lip, chin, chest, upper or lower back, upper or lower abdomen, upper arms and thighs [16].…”

Effects of metformin on the adrenal cortex of androgenized rats

“…The increase in androgens from the ovaries and the adrenal glands is usual in PCOS due to the heightened activity of 17-hydroxylase and 17-20-lyase in the conversion of progesterone into 17-hydroxyprogesterone and of 17-hydroxypregnenolone into androstenedione [5]. There is a great deal of evidence of metformin action on PCOS, and this could manifest as changes in folliculogenesis and a decrease in androgen production [6,7].…”