Glucagon‐like peptide‐1 reduces the pulsatile component of testosterone secretion in healthy males

Abstract

Glucagon-like-peptide-1 (7-36) amide (GLP-1), a potent regulator of glucose homeostasis, has been implicated in the control of hypothalamic-pituitary function. In vivo it is a relevant neuroendocrine modulator of gonadotropin-releasing hormone release, suggesting its possible role as a metabolic signal to the reproductive system. The present study was undertaken to establish its effect on luteinizing hormone (LH) and testosterone secretion in nine healthy male volunteers. Each subject underwent an oral glucose tolerance test to establish LH, testosterone, and GLP-1 responses to glucose. Euglycaemic clamp experiments (6 h) were performed on two occasions with saline or with a constant infusion of GLP-1 (0.4 pmol kg(-1) min (-1)). Blood samples were drawn at 10-min intervals to measure the pulsatile pattern of LH and testosterone secretion. Ingestion of oral glucose resulted in a reduction in plasma testosterone levels at 30 min compared with baseline (P < 0.004) despite unaltered LH levels (P = 0.5). Constant GLP-1 infusion resulted in no change in LH (P = 0.83), testosterone (P = 0.96), follicle stimulating hormone (FSH) (P = 0.86) and leptin levels (P = 0.3). Pulse analysis revealed no significant difference in the number (P = 0.1) or median absolute amplitude (P = 0.3) of the LH pulses. However, there was a significant decrease in the number (3.0 +/- 0.6 vs. 1.3 +/- 0.4; P < 0.05) and a tendency for increased duration of testosterone pulses (97.4 +/- 16.7 vs. 170 +/- 27.1 min; P = 0.06). Oral glucose ingestion and intravenous GLP-1 infusion reduce the pulsatile component of testosterone secretion by a mechanism independent of LH release.