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

RATNER D; MARCIAL LOPEZ A; SUAREZ ORTEGA A; ALZAMENDI A; GIOVAMBATTISTA A; HUHTANIEMI IT; SPINEDI E; CALANDRA RS; RULLI SB

Orlando

Congreso; 2017 ENDO Meeting; 2017

ESO

Male hypogonadism is characterized by androgen deficiency and infertility. Androgen replacement therapy inprepubertal boys and men induces and maintains normal secondary sexual characteristics, sexual function, andbehavior. 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 hCGtherapy on metabolic pathways has not been fully investigated, experimental studies on this topic need to beexplored. Recent investigations in female mice have shown the impact of the overexpression of hCG on thecarbohydrates and lipid metabolism (1). In addition, we have assessed that transgenic male mice overexpressinghCGβ subunit (hCGβ+) are fertile and have normal plasma testosterone levels, with minor disturbances of thegonadal axis (2). Conversely, males overexpressing α and β subunits of hCG (hCGαβ+) are infertile and exhibitelevated serum levels of androgens. The aim of this study was to analyze the influence of hCG on both glucose andlipid 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) wereperformed. Finally, pancreas, liver and white adipose tissue histological analyses were performed. Transgenic malesfrom both groups displayed normal plasma levels of insulin, triglycerides and cholesterol. hCGβ+ mice showedincreased serum leptin levels, food intake and BW vs WT mice (p < 0.01). Alterations in the GTT were observed inboth groups (p < 0.05), whereas only hCGαβ+ mice developed insulin resistance. Hypertrophic white adipose tissuemass was noticed in both transgenic mice, whereas pancreatic and liver cell morphology remained normal. Theseresults indicated that early and chronic hCG exposure induced a clearly disturbed glucose metabolism, although noeffect on lipid metabolism appeared. Our study highlights that mainly carbohydrate metabolic aspects in patientsunder long-term hCG therapy due to hypogonadism, should be carefully monitored.