关键词: 青春期, 早熟；中枢性性早熟；miR-125b；维生素D；促性腺激素释放激素类似物；乳房发育

Abstract: Background　Premature activation of hypothalamic-pituitary-gonadal axis is the main mechanism of central precocious puberty（CPP），but the mechanism of its activation is still unclear.mi-RNA may be involved in the development of precocious puberty.Objective　 To explore the relationships of serum microRNA-125b and vitamin D and hormone parameters，and analysis the clinical significance of combined detection of serum miR-125b and vitamin D.Methods　We enrolled 102 CPP female children（CPP group） and 102 age- and sex-matched physical examinees（control group） from Boai Hospital of Zhongshan Affiliated to Southern Medical University from July to September，from 2013 to 2016.The clinical parameters，such as age，height，weight，body mass index （BMI），breast development age，ovarian volume，bone age，bone age and age difference，WSDS，HSDS，and BMI SDS and distribution of Tanner stage were recorded.The expression level of miR-125b was detected by qRT-PCR.And the levels of 25-hydroxy-vitamin D（25-OH-D） and hormone parameters（free thyroxine，thyrotropin，estradiol，prolactin，luteinizing hormone and follicle-stimulating hormone）were detected using chemiluminiscence assay.Results　The expression level of serum miR-125b was higher in CPP group than that in the control group （P<0.05）．The serum miR-125b expression level was negatively correlated with 25-OH-D level in CPP group （r=-0.809 5，P<0.01）．CPP children with high miR-125b expression（high miR-125b expression subgroup，n=54） and those with low to medium miR-125b expression（low to medium miR-125b expression subgroup，n=48） showed significant differences in the mammogenesis age and distribution of Tanner stage（P<0.05），but not in the age，ovarian volume，bone age，bone age and age difference，WSDS，HSDS，and BMI SDS （P>0.05）．Moreover，high miR-125b expression subgroup had higher estradiol level than low to medium miR-125b expression subgroup（P<0.05）．After treated by gonadotropin-releasing hormone analogues（GnRHa），high miR-125b expression patients with normal vitamin D level had higher proportion of regression of breast development than those patients with decreased vitamin D level（P<0.05），but similar improvement in decreased growth velocity and early bone development（P>0.05）．Low to medium miR-125b expression patients with normal vitamin D level and those with decreased vitamin D level had no significant differences in the improvement in prepubertal mammogenesis，decreased growth velocity and early bone development（P>0.05）．Conclusion　The expression level of miR-125b was increased in CPP female children，which was negatively correlated with vitamin D level，and affected mammogenesis age.These may be related to the upregulation of estradiol.Combined detection of miR-125b and vitamin D could predicate the effect of GnRHa therapy on allometric growth of mammary parenchyma before puberty.

Key words: Puberty, precocious；Central precocious puberty；miR-125b；Vitamin D；Gonadotropin-releasing hormone analogues；Breast development