Chronic subcutaneous kisspeptin-10 stimulates gonadotropin secretion for 12 days in healthy men
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ID: 323644
2026
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Abstract
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: (i) characterize the acute dose-response relationship to subcutaneous kisspeptin-10 infusion, (ii) assess the effects of continuous kisspeptin-10 infusion over 5-days, (iii) daily intermittent administration (8-hours on, 16-hours 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-hour 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-hour infusions at 150 nmol/h for 12-days. RESULTS: (i) Acute subcutaneous kisspeptin-10 infusions dose-dependently increased LH, FSH, and testosterone vs vehicle (p<0.0001). (ii) Although testosterone concentrations remained elevated after 5-days of continuous kisspeptin-10, gonadotropin concentrations were similar to vehicle. (iii) Daily 8h 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=0.003 vs vehicle). Following 12-days, gonadotropin rises were still detected after kisspeptin-10 bolus (1nmol/kg) indicating that the kisspeptin receptor remained functional. CONCLUSIONS: We demonstrate that chronic subcutaneous kisspeptin administration sustain 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.
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| Authors | Arthur C. Yeung, Maria Phylactou, Kanyada Koysombat, Jovanna Tsoutsouki, Sandhi Nyunt, Megan Young, Aaran Patel, Elisabeth Daniels, Aureliane C S Pierret, Edouard G Mills, Alexander Comninos, Ali Abbara, Waljit S. Dhillo |
| Journal | european journal of endocrinology |
| Year | 2026 |
| DOI |
10.1093/ejendo/lvag134
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| URL | |
| Keywords | Keywords not found |
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