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Hepatic actions of androgens in the regulation of metabolism

Birzniece, Vitaa,b,c,d

Current Opinion in Endocrinology & Diabetes and Obesity: June 2018 - Volume 25 - Issue 3 - p 201–208
doi: 10.1097/MED.0000000000000405
ANDROGENS: Edited by David Handelsman

Purpose of review The purpose of this review is to summarize recent findings on hepatic actions of androgens in the regulation of protein, lipid and glucose metabolism. The rationale for liver-targeted testosterone use will be provided.

Recent findings Liver-targeted testosterone administration, via the oral route, induces protein anabolic effect by reducing the rate of protein oxidation to a similar extent to that of systemic testosterone administration. Recent evidence indicates that testosterone exerts whole-body anabolic effect through inhibition of nitrogen loss via the hepatic urea cycle. Several hepatic effects of androgens, particularly on glucose metabolism, are direct and take place before any changes in body composition occur. This includes an increase in insulin secretion and sensitivity, and reduction in hepatic glucose output by testosterone. Furthermore, lack of testosterone in the liver exacerbates diet-induced impairment in glucose metabolism. In the liver, androgens induce the full spectrum of metabolic changes through interaction with growth hormone or aromatization to estradiol.

Summary Liver-targeted testosterone therapy may open up a new approach to achieve whole-body anabolism without systemic side-effects. Aromatizable androgens may be superior to nonaromatizable androgens in inducing a complex spectrum of direct, estrogen-mediated and other hormone-mediated effects of androgens.

aSchool of Medicine, Western Sydney University, Sydney

bDepartment of Diabetes and Endocrinology, Blacktown Hospital, Blacktown

cGarvan Institute of Medical Research, Sydney

dSchool of Medicine, University of New South Wales, Sydney, New South Wales, Australia

Correspondence to Dr Vita Birzniece, School of Medicine, Western Sydney University, Blacktown Clinical School and Research Centre, Blacktown Hospital, Blacktown 2148, NSW, Australia. Tel: +61 2 98516059; fax: +61 2 98516050; e-mail: v.birzniece@westernsydney.edu.au

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