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Published on: August 25, 2023
Chronic subcutaneous kisspeptin-10 stimulates gonadotropin secretion for 12 days in healthy men
Arthur C Yeung1, Maria Phylactou1,2, Kanyada Koysombat1,2
1Section of Endocrinology and Investigative Medicine, Department of Metabolism, Digestion and Reproduction, Imperial College London, Hammersmith Hospital, London W12 0NN, United Kingdom.
Objective:
To develop a protocol for chronic kisspeptin administration that persistently stimulates gonadotropin secretion. We evaluated the effects of acute and chronic subcutaneous kisspeptin-10 administration on reproductive hormones in healthy men to (1) characterize the acute dose--response relationship to subcutaneous kisspeptin-10 infusion, (2) assess the effects of continuous kisspeptin-10 infusion over 5 days, and (3) daily intermittent administration (8 h on, 16 h off) for 12 days.
Design:
Randomized, single-blinded, placebo-controlled study.
Methods:
Overall, 15 healthy men were recruited (study 1: n = 7, study 2: n = 4; study 3: n = 7); 12 men served as controls. Luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone were assessed during an acute 8 h dose-response subcutaneous kisspeptin-10 infusions (1.25-10.0 nmol/kg/h). Thereafter, we evaluated chronic subcutaneous administration, including continuous kisspeptin-10 infusion at 180 nmol/h for 5 days, and daily 8 h infusions at 150 nmol/h for 12 days.
Results:
(1) Acute subcutaneous kisspeptin-10 infusions dose-dependently increased LH, FSH, and testosterone vs vehicle (P < .0001). (2) Although testosterone concentrations remained elevated after 5 days of continuous kisspeptin-10, gonadotropin concentrations were similar to vehicle. (3) Daily 8 h subcutaneous infusions over 12 days sustained increases in gonadotropins (mean LH increase: vehicle -0.16 ± 0.19; day 1: +1.68 ± 0.25; day 12: +1.14 ± 0.33, P = .003 vs vehicle). Following 12 days, gonadotropin rises were still detected after kisspeptin-10 bolus (1 nmol/kg) indicating that the kisspeptin receptor remained functional.
Conclusions:
We demonstrate that chronic subcutaneous kisspeptin administration sustains gonadotropin and testosterone secretion in healthy men for 12 days. These data can inform development of chronic kisspeptin administration protocols for the treatment of reproductive disorders.
