维生素D缺乏与儿童中枢性性早熟关系研究进展

doi:10.11852/zgetbjzz2023-0209

摘要/Abstract

摘要： 中枢性性早熟(CPP)是由于下丘脑-垂体-性腺轴功能提前启动,导致促性腺激素释放激素脉冲分泌增强,使内外生殖器发育和第二性征呈现的儿童内分泌疾病。研究发现维生素D缺乏可能与CPP的发病有关,维生素D可能会受到日照时间的影响、作用下丘脑-垂体-性腺轴上的神经元及神经递质、促进肥胖形成、影响胰岛素样生长因子-1的表达水平这4个因素参与CPP的发生发展,维生素D联合促性腺激素释放激素类似物治疗CPP的总体效果显著。本文就维生素D缺乏与CPP的相关性以及可能的作用机制做一综述,以期为研究者提供一定的理论依据。

关键词: 维生素D, 中枢性性早熟, 儿童

Abstract: Central precocious puberty (CPP) is an endocrine disease of children due to the early onset of hypothalamic-pituitary-gonadal axis function. This leads to increased secretion of gonadotropin release impulse, causing the development of internal and external genitalia and the presentation of secondary sex characteristics. Studies have found that the onset of CPP in children may be related to vitamin D deficiency. Vitamin D, affected by sunlight duration, acts on neurons and neurotransmitters in the hypothalamic-pituitary-gonadal axis, promotes obesity and affects the expression level of insulin-like growth factor-1, which are four factors involved in the occurrence and development of CPP. The overall effect of vitamin D combined with gonadotropin-releasing hormone analogues on CPP is significant. This article reviews the correlation between vitamin D deficiency and CPP, as well as the possible mechanism of action, in order to provide some theoretical basis for researchers.

Key words: vitamin D, central precocious puberty, child

中图分类号:

R725.8

刘小琪, 王琨蒂, 王君, 李泽铖. 维生素D缺乏与儿童中枢性性早熟关系研究进展[J]. 中国儿童保健杂志, 2024, 32(1): 59-63.

LIU Xiaoqi, WANG Kundi, WANG Jun, LI Zecheng. Research progress in the relationship between vitamin D deficiency and central precocious puberty in children[J]. Chinese Journal of Child Health Care, 2024, 32(1): 59-63.

参考文献

[1] 中华医学会儿科学分会内分泌遗传代谢学组,中华儿科杂志编辑委员会.中枢性性早熟诊断与治疗专家共识(2022)[J].中华儿科杂志,2023, 61(1): 16-22.
The Subspecialty Group of Endocinologic, Hereditary and Metabolic Diseases, the Society of Pediatrics, Chinese Medical Association, the Editorial Board, Chinese Journal of Pediatrics. Expert consensus on the diagnosis and treatment of central precocious puberty (2022)[J]. Chin J Pediatr,2023, 61(1): 16-22. (in Chinese)
[2] Eckert-Lind C, Busch AS, Petersen JH, et al. Worldwide secular trends in age at pubertal onset assessed by breast development among girls: A systematic review and Meta-analysis[J]. JAMA Pediatr, 2020, 174(4): e195881.
[3] Savastio S, Cinquatti R, Tagliaferri F, et al. Vitamin D effects and endocrine diseases[J]. Minerva Pediatr, 2020, 72(4): 326-339.
[4] Zakharova I, Klimov L, Kuryaninova V, et al. Vitamin D insufficiency in overweight and obese children and adolescents[J]. Front Endocrinol (Lausanne), 2019, 10: 103.
[5] Censani M, Hammad HT, Christos PJ, et al. Vitamin D deficiency associated with markers of cardiovascular disease in children with obesity[J].Glob Pediatr Health, 2018, 5: 2333794x17751773.
[6] Bueno AC,Stecchini MF,Marrero-Gutiérrez J, et al.Vitamin D receptor hypermethylation as a biomarker for pediatric adrenocortical tumors[J]. Eur J Endocrinol, 2022, 186(5): 573-585.
[7] Liu S, Zhu X, Wang Y, et al. The association between vitamin D levels and precocious puberty:A Meta-analysis[J].J Pediatr Endocrinol Metab,2020,33(3): 427-429.
[8] 程艳,冯艳静,黄爽,等.血清维生素D水平与女童中枢性性早熟相关性的Meta分析[J].中国性科学,2021, 30(7): 129-133.
Cheng Y, Feng YJ,Huang S, et al. The association between serum vitamin D level and central precocious puberty in girls: A Meta-analysis[J].Chinese Journal of Human Sexuality, 2021, 30(7): 129-133. (in Chinese)
[9] 倪娜,苏恒,孔祥阳.浅谈中枢性性早熟的发病机制[J].中国生物化学与分子生物学报, 2021, 37(6): 727-732.
Ni N,Su H,Kong XY.Discussion on the pathogenesis of central precocious puberty[J].Chinese Journal of Biochemistry and Molecular Biology,2021, 37: 727-732.(in Chinese)
[10] Brito VN,Canton APM,Seraphim CE,et al.The congenital and acquired mechanisms implicated in the etiology of central precocious puberty[J].Endocr Rev, 2023, 44(2):193-221.
[11] Grivas TB,Vasiliadis E,Mouzakis V,et al.Association between adolescent idiopathic scoliosis prevalence and age at menarche in different geographic latitudes[J]. Scoliosis, 2006, 1(1): 1-12.
[12] Dossus L, Kvaskoff M, Bijon A, et al. Latitude and ultraviolet radiation dose in the birthplace in relation to menarcheal age in a large cohort of French women[J]. Int J Epidemiol, 2013, 42(2): 590-600.
[13] Khalid A, Qaisar R, Hussain MA, et al. Circulating follicle stimulating hormone levels influence body growth in pre-menarcheal girls in a latitude-dependent manner[J]. Heliyon, 2023, 9(4): e15293.
[14] Bandeira F, Griz L, Dreyer P, et al. Vitamin D deficiency: A global perspective[J]. Arq Bras Endocrinol Metabol, 2006, 50(4): 640-646.
[15] Bonjour JP, Chevalley T. Pubertal timing, bone acquisition, and risk of fracture throughout life[J]. Endocr Rev, 2014, 35(5): 820-847.
[16] Nicholas C, Davis J, Fisher T, et al. Maternal vitamin D deficiency programs reproductive dysfunction in gemale mice offspring through adverse effects on the neuroendocrine axis[J]. Endocrinology, 2016, 157(4): 1535-1545.
[17] Bhattarai P, Bhattarai JP, Kim MS, et al. Non-genomic action of vitamin D3 on N-methyl-D-aspartate and kainate receptor-mediated actions in juvenile gonadotrophin-releasing hormone neurons[J].Reprod Fertil Dev,2017,29(6): 1231-1238.
[18] Gezen-Ak D, Dursun E, Yilmazer S. The effects of vitamin D receptor silencing on the expression of LVSCC-A1C and LVSCC-A1D and the release of NGF in cortical neurons[J]. PloS One, 2011, 6(3): e17553.
[19] Zanatta L,Goulart PB, Gonçalves R, et al.1α,25-dihydroxyvitamin D(3) mechanism of action: Modulation of L-type calcium channels leading to calcium uptake and intermediate filament phosphorylation in cerebral cortex of young rats[J]. Biochim Biophys Acta, 2012, 1823(10): 1708-1719.
[20] Radwan RA, Abuelezz NZ, Abdelraouf SM, et al. Decreased serum level of gamma-amino butyric acid in egyptian infertile females with polycystic ovary syndrome is correlated with dyslipidemia, total testosterone and 25(OH) vitamin D levels[J]. J Med Biochem, 2019, 38(4): 512-518.
[21] Dedes I. Kisspeptins and the control of gonadotrophin secretion[J]. Syst Biol Reprod Med, 2012, 58(3): 121-128.
[22] Roa J, Castellano JM, Navarro VM, et al. Kisspeptins and the control of gonadotropin secretion in male and female rodents[J]. Peptides, 2009, 30(1): 57-66.
[23] Nimitphong H, Guo W, Holick MF, et al. Vitamin D inhibits adipokine production and inflammatory signaling through the vitamin D receptor in human adipocytes[J]. Obesity (Silver Spring), 2021, 29(3): 562-568.
[24] Kaneko I,Sabir MS,Dussik CM,et al.1,25-dihydroxyvitamin D regulates expression of the tryptophan hydroxylase 2 and leptin genes: Implication for behavioral influences of vitamin D[J]. FASEB J, 2015, 29(9): 4023-4035.
[25] Hajimohammadi M, Shab-Bidar S, Neyestani TR. Vitamin D and serum leptin:A systematic review and Meta-analysis of observational studies and randomized controlled trials[J]. Eur J Clin Nutr, 2017, 71(10): 1144-1153.
[26] Karonova T, Belyaeva O, Jude EB, et al. Serum 25(OH)D and adipokines levels in people with abdominal obesity[J]. J Steroid Biochem Mol Biol, 2018, 175: 170-176.
[27] Karimi E, Arab A, Rafiee M, et al. A systematic review and meta-analysis of the association between vitamin D and ovarian reserve[J]. Sci Rep, 2021, 11(1): 16005.
[28] 孙菊娣.血清维生素D水平与女童特发性中枢性性早熟的相关性[J].临床与病理杂志, 2020, 40(1): 86-89.
Sun JD. Correlation between serum vitamin D level a and idiopathic central precocious puberty in girls[J]. Journal of Clinical and Pathological Research, 2020, 40(1): 86-89.(in Chinese)
[29] Esposito S, Leonardi A, Lanciotti L, et al. Vitamin D and growth hormone in children: a review of the current scientific knowledge[J]. J Transl Med, 2019, 17(1): 87.
[30] Dees WL, Hiney JK, Srivastava VK. IGF-1 influences gonadotropin-releasing hormone regulation of puberty[J]. Neuroendocrinology,2021,111(12):1151-1163.
[31] Cannarella R, Paganoni AJJ, Cicolari S, et al. Anti-müllerian hormone, growth hormone, and insulin-like growth factor 1 modulate the migratory and secretory patterns of GnRH neurons[J]. Int J Mol Sci, 2021,22(5):2445.
[32] Escagedo PD, Deal CL, Dwyer AA, et al. Insulin-like growth factor 1, but not insulin-like growth factor-binding protein 3, predicts central precocious puberty in girls 6-8 years old: A retrospective study[J]. Horm Res Paediatr, 2021, 94(1-2): 44-51.
[33] 梁珍花,戴艺,陶美娇,等.血清维生素D水平与女童ICPP的相关性研究[J].中国卫生标准管理, 2020, 11(2): 5-8.
Liang ZH, Dai Y, Tao MJ, et al. The correlation between serum vitamin D level and ICPP in girls[J]. China Health Standard Management, 2020, 11(2): 5-8. (in Chinese)
[34] Marwaha RK, Garg MK, Gupta S, et al. Association of insulin-like growth factor-1 and IGF binding protein-3 with 25-hydroxy vitamin D in pre-pubertal and adolescent Indian girls[J]. J Pediatr Endocrinol Metab, 2018, 31(3): 289-295.
[35] Gannagé-Yared MH, Chahine E, Farah V, et al. Serum insulin-like growth factor 1 in lebanese schoolchildren and its relation to vitamin D and ferritin levels[J]. Endocr Pract, 2017, 23(4): 391-398.
[36] Liu G, Guo J, Zhang X, et al. Obesity is a risk factor for central precocious puberty:A case-control study[J]. BMC Pediatr, 2021,21(1): 509.
[37] 李艳辉,董彬,邱爱明,等.男生营养状况与青春期启动的关联性[J].中国学校卫生, 2020, 41(6): 807-810.
Li YH, Dong B, Qiu AM. sociation between nutritional status and puberty onset in boys[J].Chin J Sch Health, 2020, 41(6): 807-810. (in Chinese)
[38] Deardorff J, Reeves JW, Hyland C, et al. Childhood overweight and obesity and pubertal onset among Mexican-American boys and girls in the CHAMACOS longitudinal study[J]. Am J Epidemiol, 2022, 191(1):7-16
[39] Li D, Zhang B, Cheng J, et al.Obesity-related genetic polymorphisms are associated with the risk of early puberty in Han Chinese girls[J].Clin Endocrinol (Oxf), 2022, 96(3): 319-327.
[40] Heras V, Castellano JM, Fernandois D, et al. Central ceramide signaling mediates obesity-induced precocious puberty[J].Cell Metab, 2020, 32(6): 951-966.
[41] Chen T, Chen C, Wu H, et al. Overexpression of accelerates puberty in high-fat diet-fed mice through system[J]. Exp Biol Med (Maywood), 2021, 246(1): 66-71.
[42] Liu S, Zhu X, Wang Y, et al. The association between vitamin D levels and precocious puberty:A Meta-analysis[J].J Pediatr Endocrinol Metab,2020, 33(3): 427-429.
[43] Karampela I, Sakelliou A, Vallianou N, et al. Vitamin D and obesity: Current evidence and controversies[J]. Curr Obes Rep, 2021, 10(2): 162-180.
[44] Zhao Y, Long W, Du C, et al. Prevalence of vitamin D deficiency in girls with idiopathic central precocious puberty[J]. Front Med, 2018, 12(2): 174-181.
[45] Bangalore Krishna K, Fuqua JS, Rogol AD, et al. Use of gonadotropin-releasing hormone analogs in children: Update by an international consortium[J]. Horm Res Paediatr, 2019, 91(6): 357-372.
[46] 陈华琴,邓肖君,伍金华.中枢性性早熟女童治疗过程中维生素D浓度的变化及意义[J]. 中国当代医药, 2018, 25(20): 107-109.
Chen HQ,Deng XJ,Wu JH. Changes and significance of vitamin D in th e treatment of girls with central precocious puberty[J]. China Modern Medicine, 2018, 25(20): 107-109. (in Chinese)
[47] 郑洁华.GnRHa联合维生素D₃治疗性早熟患儿的疗效探讨[J].中国处方药, 2021, 19(7): 85-86.
Zheng JH.Discussion on the efficacy of GnRHa combi ned with vitamin D3 in the treatment of patients with preco ocious puberty[J]. Journal of China Prescription Drug, 2021, 19(7): 85-86. (in Chinese)
[48] 张荣华,孙志豪,谢小燕.维生素D联合曲普瑞林对性早熟女童的治疗效果[J].中国当代医药, 2019, 26(34): 87-91.
Zhang RH, Sun ZH, Xie XY.Therapeutic effect of vitamin D combined with triptorelin on girls with precocious puberty[J].China Modern Medicine,2019,26(34): 87-91. (in Chinese)
[49] 孙燕,曹佳妍,杨洁.维生素D联合GnRHa对特发性性早熟患儿的促生长素轴与生长速度的影响[J].中国性科学, 2021, 30(7): 137-140.
Sun Y,Cao JY,Yang J. Effects of vitamin D combined with GnRHa on the growth promoting hormone axis and growth rate of children with idiopathic precocious puberty[J]. Chinese Journal of Human Sexuality, 2021, 30(7): 137-140. (in Chinese)
[50] 毛静媛,李明,潘聪,等.维生素D与促性腺激素释放激素类似物联合治疗特发性中枢性性早熟的效果及安全性分析[J].北方药学, 2021, 18(4): 84-86.
Mao JY, Li M, Pan C, et al. Efficacy and safety analysis of combination of vitamin D and gonadotropin-releasing hormone analogues in the treatment of idiopathic central precocious puberty[J]. Journal of North Pharmacy, 2021, 18(4): 84-86. (in Chinese)