Longitudinal Changes in Serum DLK1 Concentrations During Pubertal Transition in Healthy Girls and in girls with Precocious Puberty during GnRHa treatment

Lea Vilmann; Holmboe Stine A.; Kaspar Sørensen; Anders Juul; Casper Hagen

RFC3.4

Prev Next

Section Contents Cite

ESPE Abstracts (2024) 98 RFC3.4

ESPE2024 Rapid Free Communications Pituitary, Neuroendocrinology and Puberty 1 (6 abstracts)

Longitudinal Changes in Serum DLK1 Concentrations During Pubertal Transition in Healthy Girls and in girls with Precocious Puberty during GnRHa treatment

Lea Vilmann ^1,2 , Stine A. Holmboe ^1,2 , Kaspar Sørensen ^1,2 , Anders Juul ^1,2,3 & Casper Hagen ^1,2

Author affiliations

¹Department of Growth and Reproduction, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark. ²The International Research and Research Training Centre in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. ³Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark

Paternally inherited mutations in the DLK1 (delta-like non-canonical Notch ligand 1) gene cause central precocious puberty (CPP) with a metabolic phenotype, suggesting that DLK1 (Delta-like 1 homolog/Preadipocyte factor 1) may link pubertal timing with body composition. However, little is known about circulating DKL1 in normal and precocious puberty.

Objective: To evaluate longitudinal changes in circulating DLK1 concentrations in healthy girls during pubertal transition as well in girls with precocious puberty before, during and after treatment with gonadotropin-releasing hormone analogue (GnRHa).

Method: A nested longitudinal cohort of 15 healthy girls from The Copenhagen Puberty Study II (2005-2007) and 15 girls with central precocious puberty receiving GnRHa treatment. Pubertal development was described according to Tanner staging including palpation of glandular breast tissue. Serum concentrations of DLK1 was measured by a commercially available ELISA (Immuno-Biological Laboratories, Inc (IBL-America), Minneapolis, USA).

Results: Serum DLK1 in girls was detectable in all available longitudinal samples (100% > LOD) from both healthy girls (n = 123) and in girls with CPP (n = 54). In healthy girls, serum DLK1 concentrations declined from one year prior to pubertal onset to a) first examination after pubertal onset as well as b) to the last pubertal evaluation: median (range) 10.4 (7.3-14.8) vs a) 9.2 (6.5-13.4) and b) 9.8 (3.23-13.89) (ng/ml), P = .004 and P = .006, respectively. In CPP girls, baseline age and DLK1 levels were: median (range) 8.9 (7.5-9.9) years and 13.1 (7.1-18.44) ng/ml, respectively. DLK1 in aged matched healthy girls (near 8.9 years) was similar: median (range) 9.8 (6.9-21.1), P = .2. Before treatment, girls with CPP had higher DLK1 levels compared to healthy girls at first evaluation after pubertal onset: 13.1 (7.1-18.4) vs 9.2 (6.5-13.4), P = .004. In girls with CPP, DLK1 was not affected by GnRHa treatment: before treatment: 13.1 (7.1-18.4) vs 3 months after start of treatment: 11.6 (5.9-17.2), P = .8 vs. after end of treatment: 12.4 (9.4-16.1), P = .4.

Conclusion: In healthy girls, DLK1 declined significantly prior to pubertal onset. In CPP girls, DLK1 was not influenced by GnRHa treatment. Our results support that DLK1 plays a role in regulating activity of the HPG axis.