OR02-05 The Role of Ovaries in the Pathophysiology of Polycystic Ovary Syndrome Induced by Androgen Excess

Abstract Disclosure: H. Noguchi: None. Y. Yamamoto: None. M. Arata: None. K. Tamura: None. H. Aoki: None. A. Takeda: None. S. Minato: None. R. Kinouchi: None. K. Yoshida: None. T. Matsuzaki: None. T. Iwasa: None. OBJECTIVE:Androgen excess is thought to play a crucial role in the onset and progression of polycystic ovary syndrome (PCOS), although the underlying mechanism remains unclear. Recently, several studies have suggested that the pathophysiologic effects of androgens may vary by age and sex. We recently established a new PCOS model in rats, which more closely reproduces human PCOS phenotypes than conventional models. In the present study, we used our new PCOS rat model to evaluate the interaction between estrogen and androgens, similar to the pathophysiologic state of women with PCOS, in order to elucidate the mechanism underlying the formation and progression of PCOS. More specifically, we examined whether the presence of ovaries is essential in the pathophysiology of androgen-induced PCOS. MATERIALS AND METHODS:At 26 days of age, female rats were divided into two primary groups: bilaterally ovariectomized (OVX) and sham-operated (Intact). Each group was further divided into PCOS and Control groups. Based on our previous study, rats in the PCOS group were implanted with a silicon tube filled with diluted dihydrotestosterone (DHT). The DHT was dissolved in a solution of 80% peanut oil and 20% ethanol to a concentration of 16 mg/mL. In the Control group, by contrast, the rats were implanted with an empty tube. Body weight and food intake were measured weekly. At 58 and 59 days of age, locomotor activity and body temperature were measured. At 87 days of age, brain, blood, and fat tissues were collected and their gene expressions were analyzed. RESULTS: The Intact-PCOS group, compared to the Intact-Control group, exhibited increased ovarian weight, polycystic ovarian morphology, and acyclic or irregular estrous cycles, highly replicating the PCOS phenotype. Body weight, food intake, adipocyte size, weight of visceral and subcutaneous fat, and serum leptin levels were higher in the Intact-PCOS group than the Intact-Control group, but there were no significant differences between the OVX-PCOS and OVX-Control groups. The gene expression data showed no significant differences between the groups. In the light phase, the mean locomotor activity was 29% lower in the Intact-PCOS group than in the Intact-Control group, but it was only 22% lower in the OVX-PCOS group than in the OVX-Control group. Core body temperature was significantly higher in the Intact-PCOS group than in the Intact-Control group during the dark phase, whereas there were no significant differences between the OVX-PCOS and OVX-Control groups.CONCLUSIONS:In the presence of ovaries, androgens exerted unfavorable effects on metabolic functions; however, in the absence of ovaries, these effects were not observed.IMPACT STATEMENT:The effects of androgen might depend on the estrogen milieu, suggesting that the presence of ovaries is essential in the pathophysiologic development and progression of androgen-induced PCOS. Presentation: Saturday, July 12, 2025