Stanozolol, an Anabolic-Androgenic Steroid, Modulates Expression of Receptors and Disrupts Uterine Histoarchitecture in Mus musculus

Abstract Abuse of Anabolic-Androgenic Steroids (AAS) by professional and recreational athletes for endurance performance and physique is increasing globally, consequently resulting in secondary pathophysiological effects. The present investigation aims to know the efficacy of one of the AAS, stanozolol, on uterine physiology. A total of 15 female mice were assigned to three experimental groups (n=5). ST was dosed subcutaneously (low-dose, 0.5 mg/kg bwt; high-dose, 5.0 mg/ kg bwt or 1% alcohol-baseline control) for 30 days, and treatment was withdrawn on the 31st day. Morphometric evaluation of uterus demonstrated aberrant endometrial luminal epithelial proliferation, marked by irregular branching with papillary formations. Prolonged administration of ST results in disruption of uterine organization, reflecting its deleterious impact on uterine histoarchitecture. In high-dose-treated mice, immunoexpression of ERα was downregulated in the endometrial compartment while significantly upregulated in myometrium, concomitant with increased myometrial thickness leading to myometrial hypertrophy. Results indicate the androgenic-to-anabolic efficacy of ST in myometrial compartment. ST, being a derivative of DHT, does not convert into estrogen; instead it may bind to ERα in the myometrium, suggesting a compartment-specific effect of ST on murine uterus. Furthermore, substantial hyperexpression of PRLR in both endometrium and myometrium, indicates a potential stimulatory effect of ST on AR-mediated release of PRL. High-dose ST induced a significant increase in circulating T and PRL levels, while decreasing E₂ concentrations, which reflects an altered hormonal milieu. It is inferred that prolonged treatment of ST resulted in aberrant endometrial proliferation, histoarchitectural anomalies, compartment-specific differential immunoexpression of hormone receptors in the endometrium and myometrium, and altered serum hormonal milieu.