STEROID HORMONE RECEPTORS AND NUCLEAR RECEPTOR COREGULATORS IN A POLYCYSTIC OVARY SYNDROME RAT MODEL

ACOSTA MV; BRACHO GS; IÑIGUEZ I; KASS L; BOSQUIAZZO VL

Mar del Plata

Congreso; REUNIÓN CONJUNTA SAIC SAB AAFE AACYTAL 2023; 2023

In a polycystic ovary syndrome (PCOS) rat model, we previouslydemonstrated an increased incidence of uterine epithelial and glan-dular lesions. The aim of this study was to investigate the expres-sion of steroid hormone receptors and nuclear receptor coregulatorsin the uterus of PCOS rats. Female Wistar rats were treated sub-cutaneously with sesame oil (control) or dehydroepiandrosterone6mg/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 immunohisto-chemistry. Also, real-time PCR was used to measure mRNA expres-sion levels of coregulatory molecules essential for transcriptionalregulation by these receptors, such as nuclear receptor coactivators(NCOA1 and 3) and corepressors (NCOR1 and 2). ESR1 mRNAexpression was similar among groups, whereas ERS2 mRNA ex-pression was decreased in PCOS animals. Notably, PCOS animalsshowed decreased ESR1 protein expression in the epithelium, butno difference in both the subepithelial stroma (SS) and myometri-um (M) was observed between experimental groups. No changes inPR mRNA and protein expression were observed among the studygroups. The expression of AR mRNA increased in the PCOS group,and protein expression followed the same pattern of change, main-ly in SS and M. In control epithelial cells, the AR protein was onlylocalized in the cytoplasm, whereas in PCOS animals, its expres-sion was observed in both the cytoplasm and nucleus. In addition,the transcriptional expression of nuclear receptor coregulators wasnot significantly different between experimental groups. The resultsshow that PCOS modifies the expression levels of steroid hormonereceptors in the uterus. This suggests that PCOS alters AR andESR-mediated mechanisms, which could promote the developmentof uterine abnormalities found in PCOS animals.