Insulin Signaling Displayed a Differential Tissue Specific Response to Low Dose Dihydrotestosterone in Female Mice

Abstract

Hyperandrogenemia and hyperinsulinemia are believed to play prominent roles in polycystic ovarian syndrome (PCOS). We explored the effects of low dose dihydrotestosterone (DHT) on insulin signaling in metabolic and reproductive tissues in a female mouse model. Insulin resistance in the energy storage tissues is associated with type 2 diabetes. Insulin signaling in the ovaries and pituitary either directly or indirectly stimulates androgen production. Energy storage and reproductive tissues were isolated and molecular assays were performed. Livers and WAT from DHT mice displayed lower mRNA and protein expression of insulin signaling intermediates. However, ovaries and pituitaries of DHT mice exhibited higher expression levels of insulin signaling genes/proteins. Insulin‐stimulated p‐AKT levels were blunted in the livers and WAT of the DHT mice but increased or remained the same in the ovaries and pituitaries compared to controls. Glucose uptake decreased in liver and WAT but was unchanged in pituitary and ovary of DHT mice. Plasma membrane GLUTs were decreased in liver and WAT but increased in ovary and pituitary of DHT mice. Skeletal muscle insulin signaling genes were not lowered in DHT mice compared to control. DHT mice did not display skeletal muscle insulin resistance. Insulin‐stimulated glucose transport increased in skeletal muscles of DHT mice compared to controls. DHT mice were hyperinsulinemic (HI). However, the differential mRNA and protein expression pattern was independent of hyperinsulinemia in cultured hepatocytes and pituitary cells. These findings demonstrate a differential effect of DHT on the insulin‐signaling pathway in energy storage versus reproductive tissues independent of hyperinsulinemia.Support or Funding InformationThis work was supported by the National Institutes of Health (Grants R00‐HD068130 04 to S.W. and 5T32DK007751‐18 to S.A.). Technical support was provided by the Integrated Physiology Core of the Baltimore DRTC (P30DK079637). Disclosure Summary: The authors have nothing to disclose.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.