Androgen receptor actions on AgRP neurons are not a major cause of reproductive and metabolic impairments in peripubertally androgenized mice

• DOI: 10.1111/jne.13370
• Publication Date: 2024-02-12T10:13:29Z
• Authors: Romy I. Kerbus; Caroline Decourt; Megan A. Inglis; Rebecca E. Campbell; Greg M. Anderson
• Keywords: Knockout mouse; Hyperinsulinemia; Dihydrotestosterone; Androgen Excess

Abstract Excess levels of circulating androgens during prenatal or peripubertal development are an important cause polycystic ovary syndrome (PCOS), with the brain being a key target. Approximately half women diagnosed PCOS also experience metabolic syndrome; common features including obesity, insulin resistance and hyperinsulinemia. Although large amount clinical preclinical evidence has confirmed this relationship between reproductive PCOS, mechanisms by which dysregulation unknown. Neuron‐specific androgen receptor knockout alleviates some PCOS‐like in dihydrotestosterone (DHT) mouse model, but specific neuronal populations mediating these effects undefined. A candidate population is agouti‐related peptide (AgRP)‐expressing neurons, for both function. We used well‐characterised androgenized model Cre‐loxP transgenics to investigate whether deleting receptors specifically from AgRP neurons can alleviate induced dysregulation. Androgen were co‐expressed 66% control mice, only <2% mice. The number was not altered treatments. Only 20% mice showed rescue DHT‐induced androgen‐induced anovulation acyclicity. Furthermore, did dysfunction (body weight, adiposity glucose tolerance). While we cannot rule out developmental compensation our results suggest excess does markedly influence Agrp expression dysregulate function through direct actions onto neurons.