Sex-dependent increases in oxytocin levels in response to intravenous kisspeptin in humans
- PMID: 39965102
- PMCID: PMC11886556
- DOI: 10.1093/ejendo/lvaf001
Sex-dependent increases in oxytocin levels in response to intravenous kisspeptin in humans
Abstract
Background: A clinically significant oxytocin-deficient state (OXT-D) has been established in adults with arginine vasopressin deficiency, and there is a need to develop diagnostic testing. Kisspeptin (KP) is a candidate for such a test, as KP receptors are found on oxytocinergic neurons, and KP administration increases plasma OXT in animals. We hypothesized that intravenous KP administration would increase peripheral OXT levels post-injection in healthy adults.
Methods: Kisspeptin-112-121 (KP analog, 0.24 nmol/kg bolus) was administered to 12 healthy adults (50% female). Serum OXT was measured before and 10, 20, 40, and 60 min after KP administration.
Results: Males and females did not differ significantly in age, BMI, or baseline OXT levels. Ten minutes after KP, OXT increased by 18.8% from baseline (FDR-P = .004) with a greater increase in males than females (31.9% vs 5.7%, respectively, FDR-P = .004).
Conclusions: Our data support KP as a candidate for a provocative test to identify OXT-D in males.
Clinical trial registration: Our study was registered on ClinicalTrials.gov (NCT00914823).
Keywords: kisspeptin; oxytocin deficiency; posterior pituitary; provocative test.
© The Author(s) 2025. Published by Oxford University Press on behalf of European Society of Endocrinology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.
Conflict of interest statement
Conflict of interest: F.P. and E.A.L. are inventors on US provisional patent application no. 63/467,980 (Oxytocin-based therapeutics to improve cognitive control in individuals with attention deficit hyperactivity disorder). K.K.M. has received study medication and investigator-initiated research grants from Amgen and has equity in Bristol-Myers Squibb (BMS), General Electric, Boston Scientific, and Becton Dickinson. S.B.S. has a financial interest in SeNa Therapeutics. E.A.L receives grant support and research study drug from Tonix Pharmaceuticals and receives royalties from UpToDate. E.A.L. and/or immediate family member holds stock in Thermo Fisher Scientific, Zoetis, Danaher Corporation, Intuitive Surgical, Merck and West Pharmaceutical Services.
References
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- Atila C, Holze F, Murugesu R, et al. Oxytocin in response to MDMA provocation test in patients with arginine vasopressin deficiency (central diabetes insipidus): a single-centre, case-control study with nested, randomised, double-blind, placebo-controlled crossover trial. Lancet Diabetes Endocrinol. 2023;11(7):454–464. 10.1016/s2213-8587(23)00120-1 - DOI - PubMed
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