Steroidogenic enzymes in the uterus of rats with polycystic ovary syndrome.

ACOSTA MV; BRACHO GS; ALTAMIRANO GA,; LUQUE EH; KASS L; BOSQUIAZZO VL

Congreso; LXIV Reunión Anual de la Sociedad Argentina de Investigación Clínica; 2019

Women with polycystic ovary syndrome (PCOS) have a higher rate of recurrent abortions, hyperplasia and endometrial adenocarcinoma. These effects could be associated with alterations in the tissue metabolism of steroid hormones. The aim of this study was to evaluate the uterine expression of steroidogenic genes and to investigate if these genes were regulated through androgen receptor (AR) in a rat PCOS model. Wistar rats were injected sc with sesame oil (control), dehydroepiandrosterone (DHEA) 6mg/100g bw (PCOS) or DHEA 6mg/100g + Flutamide (AR antagonist) 2mg/100g (PCOS+F) from 21 to 40 days of age. 24 hours later, blood and the uterine horns were obtained. No estrous cyclicity, hyperandrogenemia and similar estradiol serum levels were observed in PCOS and PCOS+F groups. mRNA transcripts for steroidogenic acute regulatory protein (STAR), 3a-hydroxysteroid dehydrogenase (HSD), 3b-HSD (isoforms 1, 2, 3, 5 and 7), 17b-HSD (isoforms 1, 2, 3 and 4), 5a-reductase type 1 (SRD5A1), aromatase (P450arom) and, steroid sulfatase (STS), were detected in the uterus of all experimental groups. In PCOS rats, an increase of the mRNA levels of 17b-HSD2 (converts estradiol into estrone), P450arom (converts androgens into estrone and estradiol) and SRD5A1 (converts testosterone into dihydrotestosterone) and a decrease of STAR (transport cholesterol into the mitochondria) was found compared to control rats. In PCOS+F animals, the same changes described in PCOS rats regarding SRD5A1, 17b-HSD2 and STAR enzymes were found. However, the increase in P450arom expression was not observed in PCOS+F. Present results suggest that P450arom expression is regulated by AR. The induction of 17b-HSD2 and P450arom expression in the PCOS rats, allow to propose that an increase in uterine estrogenic effects may be associated with the development of endometrial hyperplasia and/or cancer.