Dynamic Profiles of Serum Kisspeptin and DLK1 During GnRH Stimulation in Central Precocious Puberty and Premature Thelarche

This study compared how the serum neuropeptides kisspeptin and DLK1 respond to GnRH stimulation in girls with central precocious puberty versus premature thelarche. The two groups showed opposite dynamic changes at 60 minutes, but the overlap between groups was considerable, leaving diagnostic value uncertain.

Journal article — cross-sectional study. Population: Girls presenting with breast development before eight years of age, stratified into central precocious puberty or premature thelarche. Sample size: 40 girls (20 CPP, 20 PT). Interventions: gonadotropin-releasing hormone (GnRH) stimulation.

Baseline kisspeptin and DLK1 levels were not significantly different between CPP and PT. At 60 minutes, the percentage change in kisspeptin was significantly lower in CPP (median -35.74%) than PT (17.66%, P=0.042), while DLK1 was significantly higher in CPP (78.38% vs 19.22%, P<0.001). At 120 minutes, DLK1 remained significantly different (P<0.001) but kisspeptin did not (P=0.499). A positive correlation between kisspeptin and DLK1 was observed at baseline and 60 minutes.

This paper provides dynamic, time-resolved data on kisspeptin and DLK1 responses to GnRH stimulation in two closely related pubertal conditions, which is relevant for understanding neuroendocrine regulation of the HPG axis. It does not establish kisspeptin or DLK1 as clinical diagnostic biomarkers, and the authors explicitly caution against overinterpreting their diagnostic value.

Key findings

• Baseline serum kisspeptin and DLK1 levels showed no significant differences between CPP and PT groups.
• At 60 minutes post-stimulation, the percentage change in kisspeptin was significantly lower in CPP than PT (median -35.74% vs 17.66%; P=0.042).
• At 60 minutes, the percentage change in DLK1 was significantly higher in CPP than PT (78.38% vs 19.22%; P<0.001).
• At 120 minutes, the DLK1 percentage change remained significantly different (P<0.001), whereas kisspeptin showed no significant difference (P=0.499).
• A positive correlation was observed between kisspeptin and DLK1 levels at both baseline and 60 minutes.

Limitations

• The authors report considerable overlap between CPP and PT patients.
• The authors state that diagnostic potential remains uncertain and requires validation in larger, independent cohorts.
• Cross-sectional design limits assessment of temporal changes and causality.

The record

• Journal: Neuroendocrinology: 1-15
• Published: 2026-07-09
• PMID: 42424240 — DOI: 10.1159/000553516

Peptide profiles: Kisspeptin.

All indexed evidence: Kisspeptin trials & papers.

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