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Effect of a GnRH injection on kisspeptin levels in girls with suspected precocious puberty: a randomized-controlled pilot study
Örebro University, School of Medical Sciences. Department of Paediatrics, School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.ORCID iD: 0000-0003-2641-5629
Örebro University, School of Medical Sciences. Örebro University Hospital. University Health Care Research Centre.ORCID iD: 0000-0002-3425-8195
Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Paediatrics, School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden; University Health Care Research Centre, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.ORCID iD: 0000-0002-5292-4913
2025 (English)In: Journal of Pediatric Endocrinology & Metabolism (JPEM), ISSN 0334-018X, E-ISSN 2191-0251, Vol. 38, no 3, p. 288-291Article in journal (Refereed) Published
Abstract [en]

OBJECTIVES: Kisspeptin plays a major role in the onset of puberty by stimulating the gonadotropin-releasing hormone (GnRH) neurons. The aim of this study was to investigate whether GnRH inhibits kisspeptin secretion via a negative feedback mechanism and potential associations between kisspeptin levels and other hormones of importance for pubertal onset.

METHODS: Thirteen girls with suspected central precocious puberty underwent a GnRH stimulation test twice in a randomized, placebo-controlled manner. Blood was sampled up to 150 min after an IV injection of either Relefact LHRH® or saline. The levels of kisspeptin, acylated ghrelin, ultrasensitive oestradiol, luteinizing hormone (LH), follicle-stimulating hormone (FSH), insulin and glucose were analysed.

RESULTS: Baseline kisspeptin levels ranged from 9.9 to 201.6 pg/mL. Neither area under the curve for kisspeptin levels nor peaks were significantly lower after the GnRH injection compared to placebo. Baseline kisspeptin and glucose levels tended to be associated (rho=0.55, p=0.051) but no other associations were found between kisspeptin and other hormones.

CONCLUSIONS: Basal levels of kisspeptin vary widely in young girls. We found no evidence of a negative feedback mechanism of GnRH on kisspeptin in this small pilot study. The suggested association between kisspeptin and glucose levels needs further investigations.

Place, publisher, year, edition, pages
Freund Publishing House, Ltd., 2025. Vol. 38, no 3, p. 288-291
Keywords [en]
Gonadotropin-releasing hormone, hypothalamic-pituitary-gonadal axis, kisspeptin, precocious puberty
National Category
Pediatrics Endocrinology and Diabetes
Identifiers
URN: urn:nbn:se:oru:diva-118847DOI: 10.1515/jpem-2024-0606ISI: 001402565800001PubMedID: 39847034Scopus ID: 2-s2.0-85216375354OAI: oai:DiVA.org:oru-118847DiVA, id: diva2:1931379
Funder
Region Örebro CountySjukvårdsregionala forskningsrådet MellansverigeAvailable from: 2025-01-27 Created: 2025-01-27 Last updated: 2025-04-28Bibliographically approved
In thesis
1. Alterations in pubertal timing: physiological aspects and long-term consequences
Open this publication in new window or tab >>Alterations in pubertal timing: physiological aspects and long-term consequences
2025 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Puberty is initiated by a series of complex mechanisms determining the age at pubertal onset. The aim of this thesis was to increase our knowledge of the role of ghrelin and kisspeptin in puberty, to describe the clinical management of delayed puberty and to study the long-term socioeconomic consequences of delayed male puberty.

Study I and II were both based on a population of 13 girls with suspected central precocious puberty, who underwent a modified gonadotropin-releasing hormone stimulation test twice in a randomized controlled setting. Neither ghrelin nor kisspeptin plasma levels differed between the two tests up to 150 minutes. In Study I, different methods for the preservation of acylated ghrelin were studied as well, and the addition of the protease inhibitor AEBSF to precooled bloodsampling tubes, and cooled centrifugation within 30 minutes were found to result in the highest levels of acylated ghrelin.

Study III was an observational study based on a review of the medical records of 91 boys with delayed puberty in central Sweden showing that puberty nomograms are useful diagnostic instruments, and that underlying pathology is rare but psychosocial distress is common.

Study IV was a longitudinal, retrospective national cohort study, which included 1,250 men previously diagnosed with delayed puberty and 12,500 unexposed men. There was a lower likelihood of marriage or cohabitation, but no negative effects on educational achievements or labour market outcomes through early adulthood among those having had delayed puberty.

Increased knowledge of the physiology and long-term consequences alterations in pubertal timing may improve the management of pubertal

Place, publisher, year, edition, pages
Örebro: Örebro University, 2025. p. 99
Series
Örebro Studies in Medicine, ISSN 1652-4063 ; 324
Keywords
puberty, pubertal disorders, precocious puberty, delayed puberty, ghrelin, kisspeptin, socioeconomic consequences, GnRH
National Category
General Practice Pediatrics
Identifiers
urn:nbn:se:oru:diva-119355 (URN)9789175296579 (ISBN)9789175296586 (ISBN)
Public defence
2025-05-22, Örebro universitet, Campus USÖ, Tidefeltssalen, Södra Grev Rosengatan 32, Örebro, 13:00 (Swedish)
Opponent
Supervisors
Available from: 2025-02-18 Created: 2025-02-18 Last updated: 2025-05-26Bibliographically approved

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Rodanaki, MariaRask, EvaLodefalk, Maria

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