Role of Androgen Receptor in Hypothalamic Regulation of Metabolism and Reproduction

This study explored the role of androgen receptors (AR) in the hypothalamic regulation of metabolism and reproduction, focusing on the expression of AR in the mouse brain across sexes and developmental stages. It was found that AR expression changes dynamically during prepubertal development in both male and female mice. The research identified specific brain regions, such as the ventral premammillary nucleus (PMv) and arcuate nucleus (ARH), where AR is coexpressed with leptin receptor (LepRb) neurons, which are crucial for energy homeostasis and fertility. Deletion of AR from LepRb cells led to sex-specific changes in reproductive and metabolic functions, including altered hormone levels and body composition. In female mice, AR deletion in LepRb neurons improved estrous cycles under conditions of prenatal androgen excess, suggesting a potential role in mitigating polycystic ovary syndrome (PCOS) symptoms. The findings underscored the importance of LepRb neurons as targets of androgen action, contributing to sex-specific differences in neuroendocrine and metabolic regulation.