Acute effects of glucagon on reproductive hormone secretion in healthy men

Abstract

Context: Glucagon increases energy expenditure; consequently, glucagon receptor agonists arein development for the treatment of obesity. Obesity negatively affects the reproductive axis,and hypogonadism itself can exacerbate weight gain. Therefore, knowledge of the effects ofglucagon receptor agonism on reproductive hormones is important for developing therapeuticsfor obesity; but reports in the literature about the effects of glucagon receptor agonism on thereproductive axis are conflicting.Objective: The objective of this work is to investigate the effect of glucagon administration onreproductive hormone secretion in healthy young men.Design: A single-blinded, randomized, placebo-controlled crossover study was conducted.Setting: The setting of this study was the Clinical Research Facility, Imperial College HealthcareNHS Trust.Participants: Eighteen healthy eugonadal men (mean ± SEM: age 25.1 ± 1.0 years; body massindex 22.5 ± 0.4 kg/m2; testosterone 21.2 ± 1.2 nmol/L) participated in this study.Intervention: An 8-hour intravenous infusion of 2 pmol/kg/min glucagon or rate-matchedvehicle infusion was administered.Main Outcome Measures: Luteinizing hormone (LH) pulsatility; LH, follicle-stimulating hormone(FSH), and testosterone levels were measured.Results: Although glucagon administration induced metabolic effects (insulin area under thecurve: vehicle 1065 ± 292 min.μ U/mL vs glucagon 2098 ± 358 min.μ U/mL, P