Taylor B Irvine, D Ashley Monks
Sex differences in circulating androgens are well-known to organize and activate neural and behavioral sex differences of traditional animal models, but much less is known about the consequences of intrasexual differences in androgens. One approach to this question is studying the effects of hyperandrogenism in females. Hyperandrogenism is associated with several endocrine conditions affecting women, with polyendocrine metabolic ovarian syndrome (PMOS) being the most common during reproductive years. PMOS symptoms often emerge around puberty, raising the possibility of organizational effects of hyperandrogenism on neurobehavioral phenotype. Using a mouse model of PMOS, we examined how the timing of symptom induction by 5α-dihydrotestosterone (DHT) treatment affects androgen-linked sociosexual behavioral phenotype. Female mice received DHT or vehicle treatment at peripuberty (PND21) and again in adulthood (PND60), generating four treatment groups with distinct developmental treatment histories. Behavioral testing assessed social preference, stereotyped/repetitive behaviors and partnered social interactions following the first and second androgen treatment. Brain FOS following partnered interaction with an age-matched, unfamiliar female was also measured. Peripubertal DHT treatment accelerated pubertal onset, as indicated by earlier vaginal opening and increased body weight. Androgen treatment had no effect on stereotyped/repetitive behavior or FOS expression but peripubertal androgen treatment altered exploratory activity during adult social preference tests, rather than social preference per se. In partnered interaction tests, both peripubertal and adult androgens increased masculine sexual approach responses, including mounting, with minimal effects on social behavior. These results are consistent with other evidence that peripubertal androgenic mechanisms can organize neurobehavioral phenotypes.