Low Dose Dihydrotestosterone Drives Metabolic Dysfunction via Cytosolic and Nuclear Hepatic Androgen Receptor Mechanisms.

Low Dose Dihydrotestosterone Drives Metabolic Dysfunction via Cytosolic and Nuclear Hepatic Androgen Receptor Mechanisms. Endocrinology. 2016 Dec 14;:en20161553 Authors: Andrisse S, Childress S, Ma Y, Billings K, Chen Y, Xue P, Stewart A, Sonko ML, Wolfe A, Wu S Abstract Androgen excess in women is associated with metabolic dysfunction (obesity, hyperinsulinemia, insulin resistance, and increased risk of type 2 diabetes (T2D)) and reproductive dysfunction (polycystic ovaries, amenorrhea, dysregulated gonadotropin release, and infertility). We sought to identify the effects of androgen excess on glucose metabolic dysfunction and the specific mechanisms of action by which androgens are inducing pathology. We developed a mouse model that displayed pathophysiological serum androgen levels with normal body mass/composition to ensure that the phenotypes were directly from androgens and not an indirect consequence of obesity. We performed reproductive tests, metabolic tests, and hormonal assays. Livers were isolated and examined via molecular, biochemical, and histological analysis. Additionally, a low dose DHT cell model using H2.35 mouse hepatocytes were developed to study androgen effects on hepatic insulin signaling. DHT mice demonstrated impaired estrous cyclicity, few corpora lutea (CL) in the ovaries, glucose, insulin and pyruvate intolerance, and lowered hepatic insulin action. Mechanistically, DHT increased hepatic AR binding to ph...
Source: Endocrinology - Category: Endocrinology Authors: Tags: Endocrinology Source Type: research