Circulating MKRN3 levels decline during puberty in healthy boys

Abstract

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..