title: Circulating MKRN3 Levels Decline During Puberty in Healthy Boys.
abstract: Initiation and progression of puberty requires concerted action of hypothalamic activating and inhibiting factors. Recently, cases of familial central precocious puberty have been linked to loss-of-function mutations of makorin RING-finger protein 3 (MKRN3) indicating a pivotal inhibitory role of the protein on GnRH secretion.
  
  
  
  To investigate peripubertal circulating MKRN3 levels in healthy boys.
  
  
  
  Population-based longitudinal study in healthy Danish boys.
  
  
  
  General community.
  
  
  
  Healthy boys (n = 60) aged (median [range]) 9.3 (5.8-11.8) years at baseline followed for 6.0 (0.5-7.6) years (2006-2014) with blood sampling every 6 months.
  
  
  
  None.
  
  
  
  Serum levels of MKRN3: 623 samples, median (range) 12 (2-14) per boy.
  
  
  
  MKRN3 levels declined before onset of puberty; the geometric mean (95% confidence interval) 5 years before onset of puberty vs last visit before onset of puberty was 216 (169-272) pg/mL vs 128 (118-139) pg/mL (P < .001), respectively. MKRN3 levels continued to decrease as puberty progressed. MKRN3 levels were not associated with age at onset of puberty.
  
  
  
  Declining MKRN3 before pubertal onset support MKRN3 as an inhibitor of GnRH secretion during midchildhood.
authors.affiliation: Department of Growth and Reproduction, Rigshospitalet, University of Copenhagen, DK-2100 Copenhagen, Denmark; and International Center for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC).
authors.forename: Alexander S
authors.initials: AS
authors.lastname: Busch
authors.affiliation: Department of Growth and Reproduction, Rigshospitalet, University of Copenhagen, DK-2100 Copenhagen, Denmark; and International Center for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC).
authors.forename: Casper P
authors.initials: CP
authors.lastname: Hagen
authors.affiliation: Department of Growth and Reproduction, Rigshospitalet, University of Copenhagen, DK-2100 Copenhagen, Denmark; and International Center for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC).
authors.forename: Kristian
authors.initials: K
authors.lastname: Almstrup
authors.affiliation: Department of Growth and Reproduction, Rigshospitalet, University of Copenhagen, DK-2100 Copenhagen, Denmark; and International Center for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC).
authors.forename: Anders
authors.initials: A
authors.lastname: Juul
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D064368:Healthy Volunteers; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D011627:Puberty / Q000097:blood*; D012261:Ribonucleoproteins / Q000097:blood*; D044767:Ubiquitin-Protein Ligases
chemical_list: D012261:Ribonucleoproteins; C119425:MKRN3 protein, human; D044767:Ubiquitin-Protein Ligases