Effect of Endogenous Levels of Human Chorionic Gonadotropin (hCG) on Glucose and Lipid Metabolism in Male Mice

RATNER LAURA D; ALZAMENDI A; HUHTANIEMI I; SUAREZ ORTEGA A; SPINEDI E; RULLI S; MARCIAL LOPEZ A; GIOVAMBATTISTA A; CALANDRA R

Orlando

Congreso; 99° Annual Meeting Endo; 2017

Male hypogonadism is characterized by androgen deficiency and infertility. Androgen replacement therapy in prepubertal boys and men induces and maintains normal secondary sexual characteristics, sexual function, and behavior. Conversely, hCG therapy may be used in patients with hypogonadotropic hypogonadism to recover fertility, since hCG treatment stimulates spermatogenesis by inducing androgen production. Because the impact of hCG therapy on metabolic pathways has not been fully investigated, experimental studies on this topic need to be explored. Recent investigations in female mice have shown the impact of the overexpression of hCG on the carbohydrates and lipid metabolism (1). In addition, we have assessed that transgenic male mice overexpressing hCGβ subunit (hCGβ+) are fertile and have normal plasma testosterone levels, with minor disturbances of the gonadal axis (2). Conversely, males overexpressing α and β subunits of hCG (hCGαβ+) are infertile and exhibit elevated serum levels of androgens. The aim of this study was to analyze the influence of hCG on both glucose and lipid metabolism in adult transgenic mice. Food intake, body weight (BW) gain, and tryglicerides, cholesterol, glucose, insulin and leptin levels were analyzed. In addition, glucose (GTT) and insulin tolerance tests (ITT) were performed. Finally, pancreas, liver and white adipose tissue histological analyses were performed. Transgenic males from both groups displayed normal plasma levels of insulin, triglycerides and cholesterol. hCGβ+ mice showed increased serum leptin levels, food intake and BW vs WT mice (p < 0.01). Alterations in the GTT were observed in both groups (p < 0.05), whereas only hCGαβ+ mice developed insulin resistance. Hypertrophic white adipose tissue mass was noticed in both transgenic mice, whereas pancreatic and liver cell morphology remained normal. These results indicated that early and chronic hCG exposure induced a clearly disturbed glucose metabolism, although no effect on lipid metabolism appeared. Our study highlights that mainly carbohydrate metabolic aspects in patients under long-term hCG therapy due to hypogonadism, should be carefully monitored.