Steroid hormone receptors and nuclear receptor coregulators in a polycystic ovary syndrome rat model

ACOSTA, MARÍA V; BRACHO, GISELA S; IÑIGUEZ, INRI; KASS, LAURA; BOSQUIAZZO, VERÓNICA LIS

Mar del Plata

Congreso; LXVIII Reunión Anual de la Sociedad Argentina de Investigación Clínica (SAIC); 2023

Sociedad Argentina de Investigación Clínica (SAIC)

In a polycystic ovary syndrome (PCOS) rat model, we previously demonstrated an increased incidence of uterine epithelial and glandular lesions. The aim of this study was to investigate the expression of steroid hormone receptors and nuclear receptor coregulators in the uterus of PCOS rats. Female Wistar rats were treated subcutaneously with sesame oil (control) or dehydroepiandrosterone 6mg/100g bw (PCOS) from 21 to 40 days of age. After 24 hours, uterine horns were collected. Uterine expression of estrogen alpha (ESR1), estrogen beta (ESR2), progesterone (PR) and androgen (AR) receptors was analyzed by real-time PCR and immunohistochemistry. Also, real-time PCR was used to measure mRNA expression levels of coregulatory molecules essential for transcriptional regulation by these receptors, such as nuclear receptor coactivators (NCOA1 and 3) and corepressors (NCOR1 and 2). ESR1 mRNA expression was similar among groups, whereas ERS2 mRNA expression was decreased in PCOS animals. Notably, PCOS animals showed decreased ESR1 protein expression in the epithelium, but no difference in both the subepithelial stroma (SS) and myometrium (M) was observed between experimental groups. No changes in PR mRNA and protein expression were observed among the study groups. The expression of AR mRNA increased in the PCOS group, and protein expression followed the same pattern of change, mainly in SS and M. In control epithelial cells, the AR protein was only localized in the cytoplasm, whereas in PCOS animals, its expression was observed in both the cytoplasm and nucleus. In addition, the transcriptional expression of nuclear receptor coregulators was not significantly different between experimental groups. The results show that PCOS modifies the expression levels of steroid hormone receptors in the uterus. This suggests that PCOS alters AR and ESR-mediated mechanisms, which could promote the development of uterine abnormalities found in PCOS animals.