Steroidogenic enzymes in the uterus of rats with polycystic ovary syndrome

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

Mar del Plata

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

Sociedad Argentina de Investigación Clínica

Women with polycystic ovary syndrome (PCOS)have a higher rate of recurrent abortions, hyperplasia and endometrialadenocarcinoma. These effects could be associated with alterations in thetissue metabolism of steroid hormones. The aim of this study was to evaluatethe uterine expression of steroidogenic genes and to investigate if these geneswere regulated through androgen receptor (AR) in a rat PCOS model. Wistar ratswere 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 hornswere obtained. No estrous cyclicity, hyperandrogenemia and similar estradiolserum levels were observed in PCOS and PCOS+F groups. mRNA transcripts forsteroidogenic 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-reductasetype 1 (SRD5A1), aromatase (P450arom) and, steroid sulfatase (STS), weredetected in the uterus of all experimental groups. In PCOS rats, an increase ofthe mRNA levels of 17b-HSD2 (converts estradiol into estrone), P450arom(converts androgens into estrone and estradiol) and SRD5A1 (convertstestosterone into dihydrotestosterone) and a decrease of STAR (transportcholesterol into the mitochondria) was found compared to control rats. InPCOS+F animals, the same changes described in PCOS rats regarding SRD5A1, 17b-HSD2and STAR enzymes were found. However, the increase in P450arom expression wasnot observed in PCOS+F. Present results suggest that P450arom expression isregulated 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 beassociated with the development of endometrial hyperplasia and/or cancer.