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 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. CONCLUSION Declining MKRN3 before pubertal onset support MKRN3 as an inhibitor of GnRH secretion during midchildhood.