UTERINE ENDOCRINE ENVIRONMENT IN A RAT PCOS MODEL

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

Congreso; REUNIÓN CONJUNTA SAIC SAI&FAIC SAFIS 2022 LXVII REUNIÓN ANUAL DE LA SOCIEDAD ARGENTINA DE INVESTIGACIÓN CLÍNICA (SAIC); 2022

This study aimed to investigate whether the development of lesions found in the uterus of rats with polycystic ovary syndrome (PCOS) is associated with changes in the local endocrine environment. Female Wistar rats were treated subcutaneously with sesame oil (CONTROL) or dehydroepiandrosterone 6mg/100g of body weight (PCOS) from 21 to 40 days of age. After 24 hours, blood and uterine horns were collected. To analyze the uterine endocrine environment in these animals, the levels of steroid hormones [estrone (E1), estradiol (E2), progesterone (P4), and testosterone (T)] were measured in uterine tissue and serum. Also, the main steroidogenic proteins [steroidogenic acute regulatory protein (StAR), 17b-hydroxysteroid dehydrogenase isoform 2 (17b-HSD2), 5a-reductase isoform 1 (Srd5a1) and aromatase (P450arom)] and the expression of estrogen alpha (ESR1), progesterone (PR) and androgen (AR) receptors were studied in the uterus. The PCOS group showed no difference in serum levels of E2 and P4 compared to CONTROL, however, an increase in T levels was observed. In uterine tissue, E1, E2, and P4 were detected in all CONTROL animals. In the PCOS group, E2 was detected in 100%, E1 in 75%, and P4 in only 50% of the rats. Notably, T was detected in 66.7% of CONTROL, however was not found in PCOS animals. In addition, we observed decreased mRNA levels of StAR and increased expression of 17b-HSD2, Srd5a1, and P450arom in the uterus of PCOS rats. Regarding steroid receptors, only AR expression was modified, increasing in the subepithelial stroma and myometrium of the PCOS group. Our results suggest that, in the uterus of PCOS rats, androgens and estrogens come from systemic hormonal metabolism, not from de novo synthesis since StAR was decreased. Also, the undetectable T levels, the increase in P450arom, together with a lower P4 detection, suggest that P4 would not sufficiently counteract estrogenic stimulation, which could promote the development of uterine lesions.