The conversion of dehydroepiandrosterone into androst-5-ene-3β,17β-diol (androstenediol) is increased in endometria from untreated women with polycystic ovarian syndrome

• Published in: Steroids Vol. 75; no. 12; pp. 810 - 817
• Main Authors: Plaza, F., Gabler, F., Romero, C., Vantman, D., Valladares, L., Vega, M.
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Inc 01.12.2010; Elsevier
• Subjects: Androstenediol; Biological and medical sciences; Dehydroepiandrosterone; Endometrium; Female genital diseases; Fundamental and applied biological sciences. Psychology; Gynecology. Andrology. Obstetrics; Intracrinology; Medical sciences; Non tumoral diseases; PCOS; Steroid metabolism; Vertebrates: endocrinology; Steroid metabolism; Androstenediol; PCOS; Dehydroepiandrosterone; Intracrinology; Endometrium; Steroid; Female sterility; Polycystic ovary; Metabolism; Female genital diseases; Ovarian diseases; Uterus; Female genital system; Cyst; Female; Benign neoplasm
• ISSN: 0039-128X; 1878-5867
• DOI: 10.1016/j.steroids.2010.06.011

The changes in endometrial homeostasis found in women with polycystic ovarian syndrome (PCOS) could be associated with alterations in the intracrine metabolism of steroid hormones. The uptake of dehydroepiandrosterone-sulphate (DHEA-S), precursor of the intracrine pathway, is achieved by transporters, such as organic anion transporter polypeptides (OATPs), and molecules with oestrogenic activity, such as androst-5-ene-3β,17β-diol (androstenediol), can be generated. We aimed to determine androstenediol generation and the expression of OATPs in human endometria throughout the menstrual cycle and in endometria from PCOS women. Endometrial samples were obtained from control women in the proliferative phase (control endometria (CEp), n = 7), secretory phase (CEs, n = 7), and from PCOS patients (PCOSEp, n = 7). The mRNA levels of OATP-B, OATP-D and OATP-E were measured by reverse transcriptase polymerase chain reaction (RT-PCR) and protein levels of OATP-E by immunofluorescence; 3β-hydroxysteroid dehydrogenase (HSD) by immunohistochemistry/Western blot; the metabolism of DHEA to androstenediol was evaluated by thin layer chromatography–high-performance liquid chromatography (TLC–HPLC). Lower levels of OATP-E transcript were obtained in PCOSEp ( p < 0.05) compared with CEp, while OATP-E protein levels ( p < 0.05) and DHEA conversion to androstenediol ( p < 0.01) were higher in PCOSEp. Lower 3β-(hydroxysteroid dehydrogenase) HSD protein levels were found in PCOSEp ( p < 0.05) (Western blot, immunohistochemistry). These results reveal a higher capacity of the endometria from PCOS women to metabolise DHEA to androstenediol, which, coupled with the high oestrogen sensitivity previously found in these endometria, may account for the increase in cell proliferation in PCOSEp already reported.