Circulating MKRN3 levels decline during puberty in healthy boys

CONTEXT: 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.

OBJECTIVE: To investigate peripubertal circulating MKRN3 levels in healthy boys Design: Population-based longitudinal study in healthy Danish boys Setting: General community Patients or Other Participants: 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.

INTERVENTION: None Main Outcome Measures: Serum levels of MKRN3: 623 samples, median (range) 12 (2 - 14) per boy.

RESULTS: MKRN3 levels declined prior to onset of puberty; the geometric mean (95% CI) 5 years prior to onset of puberty vs. last visit before onset of puberty was 216 (169 - 272) pg/ml vs. 128 (118 - 139) pg/ml (p < 0.001), respectively. MKRN3 levels continued to decrease as puberty progressed. MKRN3 levels were not associated with age at onset of puberty.

CONCLUSION: Declining MKRN3 prior to pubertal onset support MKRN3 as an inhibitor of GnRH secretion during mid-childhood.