MKRN3 levels in girls with central precocious puberty and correlation with sexual hormone levels: a pilot study
Recently, mutations of makorin RING-finger protein 3 (MKRN3) have been described in familial central precocious puberty. Serum levels of this protein decline before the pubertal onset in healthy girls and boys. The aim of the study is to investigate MKRN3 circulating levels in patients with central precocious puberty.
We performed an observational cross-sectional study. We enrolled 17 patients with central precocious puberty aged 7 years (range: 2–8 years) and breast development onset <8 years; 17 prepubertal control age-matched patients aged 6.3 years (2–8.2); and 10 pubertal stage-matched control patients aged 11.4 years (9–14). Serum values of MKRN3, gonadotropins, (17)estradiol and Anti-Müllerian Hormone were evaluated and the MKRN3 genotyped in central precocious puberty patients.
No MKRN3 mutation was found among central precocious puberty patients. MKRN3 levels were lower in patients with central precocious puberty compared to prepubertal age-matched ones (p: 0.0004) and comparable to those matched for pubertal stage. MKRN3 levels were inversely correlated to Body Mass Index Standard Deviations (r:−0.35; p:0.02), Luteinizing Hormone (r:−0.35; p:0.03), FSH (r:−0.37; p:0.02), and (17)estradiol (r: −0.36; p:0.02).
We showed that girls with central precocious puberty had lower peripheral levels of MKRN3 compared to age-matched pairs and that they negatively correlated to gonadotropins, estrogen, and BMI. Our findings support the MKRN3 involvement in central precocious puberty also in absence of deleterious mutations, although our sample size is small.
In addition our data suggest the role of MKRN3 in the complex mechanism controlling puberty onset and its interaction with other factors affecting puberty such as nutrition.
KeywordsPuberty Genetics MKRN3 Central precocious puberty
Compliance with ethical standards
Conflict of interest
The authors declare that they have no competing interest.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Informed consent was obtained from all individual participants included in the study.
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