Generic placeholder image

Current Molecular Medicine

Editor-in-Chief

ISSN (Print): 1566-5240
ISSN (Online): 1875-5666

Review Article

The Key Roles of Makorin RING Finger Protein 3 (MKRN3) During the Development of Pubertal Initiation and Central Precocious Puberty (CPP)

Author(s): Jiang Liu, Tangluo Li, Mindan Peng, Min Luo, Zihao Gui, Shuanglian Long*, Zhongcheng Mo* and Weiguo He*

Volume 23, Issue 7, 2023

Published on: 13 September, 2022

Page: [668 - 677] Pages: 10

DOI: 10.2174/1566524022666220624105430

Price: $65

Abstract

Puberty is initiated from the continuous and growing pulsatile secretion of gonadotropin-releasing hormone (GnRH) in the hypothalamus and then the activation of the hypothalamic-pituitary-gonadal (HPG) axis. Numerous factors involve pubertal initiation, whose abnormality may come from the dysfunction of these regulators. Makorin RING finger protein 3 (MKRN3) inhibits the secretion of GnRH and plays indispensable roles during the development of pubertal onset, and mutations of MKRN3 showed the commonest genetic cause of central precocious puberty (CPP). Recently, growing studies have revealed the functional mechanisms of MKRN3 in the pubertal initiation and the occurrence of CPP. In this review, we mainly summarized the research advances on the roles of MKRN3 in the development of pubertal onset and their underpinning mechanisms, contributing to a better understanding of the precise mechanisms of pubertal initiation and the pathogenesis of CPP.

Keywords: Makorin RING finger protein 3, MKRN3, Puberty initiation, Central precocious puberty, CPP, GnRH

[1]
Tena-Sempere M. Keeping puberty on time: Novel signals and mechanisms involved. Curr Top Dev Biol 2013; 105: 299-329.
[http://dx.doi.org/10.1016/B978-0-12-396968-2.00011-7] [PMID: 23962847]
[2]
Bradley SH, Lawrence N, Steele C, Mohamed Z. Precocious puberty. BMJ 2020; 368: l6597.
[http://dx.doi.org/10.1136/bmj.l6597] [PMID: 31932347]
[3]
Ojeda SR, Lomniczi A, Mastronardi C, et al. Minireview: The neuroendocrine regulation of puberty: Is the time ripe for a systems biology approach? Endocrinology 2006; 147(3): 1166-74.
[http://dx.doi.org/10.1210/en.2005-1136] [PMID: 16373420]
[4]
Abreu AP, Kaiser UB. Pubertal development and regulation. Lancet Diabetes Endocrinol 2016; 4(3): 254-64.
[http://dx.doi.org/10.1016/S2213-8587(15)00418-0] [PMID: 26852256]
[5]
Chirico V, Lacquaniti A, Salpietro V, Buemi M, Salpietro C, Arrigo T. Central precocious puberty: From physio-pathological mechanisms to treatment. J Biol Regul Homeost Agents 2014; 28(3): 367-75.
[PMID: 25316125]
[6]
Ojeda SR, Lomniczi A, Sandau U, Matagne V. New concepts on the control of the onset of puberty. Endocr Dev 2010; 17: 44-51.
[http://dx.doi.org/10.1159/000262527] [PMID: 19955755]
[7]
Howard SR, Dunkel L. Delayed puberty-phenotypic diversity, molecular genetic mechanisms, and recent discoveries. Endocr Rev 2019; 40(5): 1285-317.
[http://dx.doi.org/10.1210/er.2018-00248] [PMID: 31220230]
[8]
Latronico AC, Brito VN, Carel JC. Causes, diagnosis, and treatment of central precocious puberty. Lancet Diabetes Endocrinol 2016; 4(3): 265-74.
[http://dx.doi.org/10.1016/S2213-8587(15)00380-0] [PMID: 26852255]
[9]
Partsch CJ, Sippell WG. Pathogenesis and epidemiology of precocious puberty. Effects of exogenous oestrogens. Hum Reprod Update 2001; 7(3): 292-302.
[http://dx.doi.org/10.1093/humupd/7.3.292] [PMID: 11392376]
[10]
Nabhan ZM, Mieszczak J, Eugster EA. Combined central precocious puberty and primary gonadal failure after treatment of childhood malignancy in two boys: A diagnostic and therapeutic conundrum. J Pediatr 2010; 157(3): 507-9.
[http://dx.doi.org/10.1016/j.jpeds.2010.04.039] [PMID: 20542283]
[11]
Kiess W, Hoppmann J, Gesing J, et al. Puberty - genes, environment and clinical issues. J Pediatr Endocrinol Metab 2016; 29(11): 1229-31.
[http://dx.doi.org/10.1515/jpem-2016-0394] [PMID: 27771625]
[12]
Jong MT, Gray TA, Ji Y, et al. A novel imprinted gene, encoding a RING zinc-finger protein, and overlapping antisense transcript in the Prader-Willi syndrome critical region. Hum Mol Genet 1999; 8(5): 783-93.
[http://dx.doi.org/10.1093/hmg/8.5.783] [PMID: 10196367]
[13]
Roberts SA, Kaiser UB. Genetics in endocrinology: Genetic etiologies of central precocious puberty and the role of imprinted genes. Eur J Endocrinol 2020; 183(4): R107-17.
[http://dx.doi.org/10.1530/EJE-20-0103] [PMID: 32698138]
[14]
Böhne A, Darras A, D’Cotta H, Baroiller JF, Galiana-Arnoux D, Volff JN. The vertebrate makorin ubiquitin ligase gene family has been shaped by large-scale duplication and retroposition from an ancestral gonad-specific, maternal-effect gene. BMC Genomics 2010; 11(1): 721.
[http://dx.doi.org/10.1186/1471-2164-11-721] [PMID: 21172006]
[15]
Abreu AP, Dauber A, Macedo DB, et al. Central precocious puberty caused by mutations in the imprinted gene MKRN3. N Engl J Med 2013; 368(26): 2467-75.
[http://dx.doi.org/10.1056/NEJMoa1302160] [PMID: 23738509]
[16]
Busch AS, Hagen CP, Almstrup K, Juul A. Circulating MKRN3 levels decline during puberty in healthy boys. J Clin Endocrinol Metab 2016; 101(6): 2588-93.
[http://dx.doi.org/10.1210/jc.2016-1488] [PMID: 27057785]
[17]
Hughes IA. Releasing the brake on puberty. N Engl J Med 2013; 368(26): 2513-5.
[http://dx.doi.org/10.1056/NEJMe1306743] [PMID: 23738512]
[18]
Varimo T, Hero M, Känsäkoski J, Vaaralahti K, Matikainen N, Raivio T. Circulating makorin ring-finger protein-3 (MKRN3) levels in healthy men and in men with hypogonadotropic hypogonadism. Clin Endocrinol 2016; 84(4): 638.
[http://dx.doi.org/10.1111/cen.13027] [PMID: 26970436]
[19]
Maione L, Naulé L, Kaiser UB. Makorin RING finger protein 3 and central precocious puberty. Curr Opin Endocr Metab Res 2020; 14: 152-9.
[http://dx.doi.org/10.1016/j.coemr.2020.08.003] [PMID: 32984644]
[20]
Naulé L, Kaiser UB. Evolutionary conservation of MKRN3 and other makorins and their roles in puberty initiation and endocrine functions. Semin Reprod Med 2019; 37(4): 166-73.
[http://dx.doi.org/10.1055/s-0039-3400965] [PMID: 31972861]
[21]
Bulcao Macedo D, Nahime Brito V, Latronico AC. New causes of central precocious puberty: The role of genetic factors. Neuroendocrinology 2014; 100(1): 1-8.
[http://dx.doi.org/10.1159/000366282] [PMID: 25116033]
[22]
Ramos CO, Macedo DB, Canton APM, et al. Outcomes of patients with central precocious puberty due to loss-of-function mutations in the MKRN3 gene after treatment with gonadotropin-releasing hormone analog. Neuroendocrinology 2020; 110(7-8): 705-13.
[http://dx.doi.org/10.1159/000504446] [PMID: 31671431]
[23]
Kota AS, Ejaz S. Precocious puberty. In: StatPearls. Treasure Island (FL): StatPearls Publishing 2021.
[24]
Li C, Lu W, Yang L, et al. MKRN3 regulates the epigenetic switch of mammalian puberty via ubiquitination of MBD3. Natl Sci Rev 2020; 7(3): 671-85.
[http://dx.doi.org/10.1093/nsr/nwaa023] [PMID: 34692086]
[25]
Li C, Han T, Li Q, et al. MKRN3-mediated ubiquitination of Poly(A)-binding proteins modulates the stability and translation of GNRH1 mRNA in mammalian puberty. Nucleic Acids Res 2021; 49(7): 3796-813.
[http://dx.doi.org/10.1093/nar/gkab155] [PMID: 33744966]
[26]
Nagae M, Uenoyama Y, Okamoto S, et al. Direct evidence that KNDy neurons maintain gonadotropin pulses and folliculogenesis as the GnRH pulse generator. Proc Natl Acad Sci USA 2021; 118(5): e2009156118.
[http://dx.doi.org/10.1073/pnas.2009156118] [PMID: 33500349]
[27]
Heras V, Sangiao-Alvarellos S, Manfredi-Lozano M, et al. Hypothalamic miR-30 regulates puberty onset via repression of the puberty-suppressing factor, Mkrn3. PLoS Biol 2019; 17(11): e3000532.
[http://dx.doi.org/10.1371/journal.pbio.3000532] [PMID: 31697675]
[28]
Berger SL, Kouzarides T, Shiekhattar R, Shilatifard A. An operational definition of epigenetics. Genes Dev 2009; 23(7): 781-3.
[http://dx.doi.org/10.1101/gad.1787609] [PMID: 19339683]
[29]
Stefanska B, MacEwan DJ. Epigenetics and pharmacology. Br J Pharmacol 2015; 172(11): 2701-4.
[http://dx.doi.org/10.1111/bph.13136] [PMID: 25966315]
[30]
Ho DH, Burggren WW. Epigenetics and transgenerational transfer: A physiological perspective. J Exp Biol 2010; 213(1): 3-16.
[http://dx.doi.org/10.1242/jeb.019752] [PMID: 20008356]
[31]
Burris HH, Baccarelli AA. Environmental epigenetics: From novelty to scientific discipline. J Appl Toxicol 2014; 34(2): 113-6.
[http://dx.doi.org/10.1002/jat.2904] [PMID: 23836446]
[32]
Jenuwein T, Allis CD. Translating the histone code. Science 2001; 293(5532): 1074-80.
[http://dx.doi.org/10.1126/science.1063127] [PMID: 11498575]
[33]
Hu H, Sun SC. Ubiquitin signaling in immune responses. Cell Res 2016; 26(4): 457-83.
[http://dx.doi.org/10.1038/cr.2016.40] [PMID: 27012466]
[34]
Hershko A, Ciechanover A. The ubiquitin system. Annu Rev Biochem 1998; 67(1): 425-79.
[http://dx.doi.org/10.1146/annurev.biochem.67.1.425] [PMID: 9759494]
[35]
Deshaies RJ, Joazeiro CA. RING domain E3 ubiquitin ligases. Annu Rev Biochem 2009; 78(1): 399-434.
[http://dx.doi.org/10.1146/annurev.biochem.78.101807.093809] [PMID: 19489725]
[36]
Margolin DH, Kousi M, Chan YM, et al. Ataxia, dementia, and hypogonadotropism caused by disordered ubiquitination. N Engl J Med 2013; 368(21): 1992-2003.
[http://dx.doi.org/10.1056/NEJMoa1215993] [PMID: 23656588]
[37]
Zhao X, Su X, Cao L, et al. OTUD4: A potential prognosis biomarker for multiple human cancers. Cancer Manag Res 2020; 12: 1503-12.
[http://dx.doi.org/10.2147/CMAR.S233028] [PMID: 32184655]
[38]
Yellapragada V, Liu X, Lund C, et al. MKRN3 interacts with several proteins implicated in puberty timing but does not influence GNRH1 expression. Front Endocrinol 2019; 10: 48.
[http://dx.doi.org/10.3389/fendo.2019.00048] [PMID: 30800097]
[39]
Han SK, Gottsch ML, Lee KJ, et al. Activation of gonadotropin-releasing hormone neurons by kisspeptin as a neuroendocrine switch for the onset of puberty. J Neurosci 2005; 25(49): 11349-56.
[http://dx.doi.org/10.1523/JNEUROSCI.3328-05.2005] [PMID: 16339030]
[40]
Rometo AM, Krajewski SJ, Voytko ML, Rance NE. Hypertrophy and increased kisspeptin gene expression in the hypothalamic infundibular nucleus of postmenopausal women and ovariectomized monkeys. J Clin Endocrinol Metab 2007; 92(7): 2744-50.
[http://dx.doi.org/10.1210/jc.2007-0553] [PMID: 17488799]
[41]
Navarro VM, Fernández-Fernández R, Castellano JM, et al. Advanced vaginal opening and precocious activation of the reproductive axis by KiSS-1 peptide, the endogenous ligand of GPR54. J Physiol 2004; 561(Pt 2): 379-86.
[http://dx.doi.org/10.1113/jphysiol.2004.072298] [PMID: 15486019]
[42]
Terasawa E, Guerriero KA, Plant TM. Kisspeptin and puberty in mammals. Adv Exp Med Biol 2013; 784: 253-73.
[http://dx.doi.org/10.1007/978-1-4614-6199-9_12] [PMID: 23550010]
[43]
Uenoyama Y, Nakamura S, Hayakawa Y, et al. Lack of pulse and surge modes and glutamatergic stimulation of luteinising hormone release in Kiss1 knockout rats. J Neuroendocrinol 2015; 27(3): 187-97.
[http://dx.doi.org/10.1111/jne.12257] [PMID: 25582792]
[44]
Han SY, McLennan T, Czieselsky K, Herbison AE. Selective optogenetic activation of arcuate kisspeptin neurons generates pulsatile luteinizing hormone secretion. Proc Natl Acad Sci USA 2015; 112(42): 13109-14.
[http://dx.doi.org/10.1073/pnas.1512243112] [PMID: 26443858]
[45]
Clarkson J, Han SY, Piet R, et al. Definition of the hypothalamic GnRH pulse generator in mice. Proc Natl Acad Sci USA 2017; 114(47): E10216-23.
[http://dx.doi.org/10.1073/pnas.1713897114] [PMID: 29109258]
[46]
Ohkura S, Takase K, Matsuyama S, et al. Gonadotrophin-releasing hormone pulse generator activity in the hypothalamus of the goat. J Neuroendocrinol 2009; 21(10): 813-21.
[http://dx.doi.org/10.1111/j.1365-2826.2009.01909.x] [PMID: 19678868]
[47]
Wakabayashi Y, Nakada T, Murata K, et al. Neurokinin B and dynorphin A in kisspeptin neurons of the arcuate nucleus participate in generation of periodic oscillation of neural activity driving pulsatile gonadotropin-releasing hormone secretion in the goat. J Neurosci 2010; 30(8): 3124-32.
[http://dx.doi.org/10.1523/JNEUROSCI.5848-09.2010] [PMID: 20181609]
[48]
Goodman RL, Hileman SM, Nestor CC, et al. Kisspeptin, neurokinin B, and dynorphin act in the arcuate nucleus to control activity of the GnRH pulse generator in ewes. Endocrinology 2013; 154(11): 4259-69.
[http://dx.doi.org/10.1210/en.2013-1331] [PMID: 23959940]
[49]
Jeong HR, Lee HS, Hwang JS. Makorin ring finger 3 gene analysis in Koreans with familial precocious puberty. J Pediatr Endocrinol Metab 2017; 30(11): 1197-201.
[http://dx.doi.org/10.1515/jpem-2016-0471] [PMID: 28988223]
[50]
Bhaskaran M, Mohan M. MicroRNAs: History, biogenesis, and their evolving role in animal development and disease. Vet Pathol 2014; 51(4): 759-74.
[http://dx.doi.org/10.1177/0300985813502820] [PMID: 24045890]
[51]
Reinhart BJ, Slack FJ, Basson M, et al. The 21-nucleotide let-7 RNA regulates developmental timing in Caenorhabditis elegans. Nature 2000; 403(6772): 901-6.
[http://dx.doi.org/10.1038/35002607] [PMID: 10706289]
[52]
Wienholds E, Kloosterman WP, Miska E, et al. MicroRNA expression in zebrafish embryonic development. Science 2005; 309(5732): 310-1.
[http://dx.doi.org/10.1126/science.1114519] [PMID: 15919954]
[53]
Chen CZ, Li L, Lodish HF, Bartel DP. MicroRNAs modulate hematopoietic lineage differentiation. Science 2004; 303(5654): 83-6.
[http://dx.doi.org/10.1126/science.1091903] [PMID: 14657504]
[54]
Messina A, Langlet F, Chachlaki K, et al. A microRNA switch regulates the rise in hypothalamic GnRH production before puberty. Nat Neurosci 2016; 19(6): 835-44.
[http://dx.doi.org/10.1038/nn.4298] [PMID: 27135215]
[55]
Ong KK, Elks CE, Li S, et al. Genetic variation in LIN28B is associated with the timing of puberty. Nat Genet 2009; 41(6): 729-33.
[http://dx.doi.org/10.1038/ng.382] [PMID: 19448623]
[56]
He C, Kraft P, Chen C, et al. Genome-wide association studies identify loci associated with age at menarche and age at natural menopause. Nat Genet 2009; 41(6): 724-8.
[http://dx.doi.org/10.1038/ng.385] [PMID: 19448621]
[57]
Zhu H, Shah S, Shyh-Chang N, et al. Lin28a transgenic mice manifest size and puberty phenotypes identified in human genetic association studies. Nat Genet 2010; 42(7): 626-30.
[http://dx.doi.org/10.1038/ng.593] [PMID: 20512147]
[58]
Sangiao-Alvarellos S, Manfredi-Lozano M, Ruiz-Pino F, et al. Changes in hypothalamic expression of the Lin28/let-7 system and related microRNAs during postnatal maturation and after experimental manipulations of puberty. Endocrinology 2013; 154(2): 942-55.
[http://dx.doi.org/10.1210/en.2012-2006] [PMID: 23291449]
[59]
Grieco A, Rzeczkowska P, Alm C, Palmert MR. Investigation of peripubertal expression of Lin28a and Lin28b in C57BL/6 female mice. Mol Cell Endocrinol 2013; 365(2): 241-8.
[http://dx.doi.org/10.1016/j.mce.2012.10.025] [PMID: 23138112]
[60]
Parent AS, Matagne V, Westphal M, Heger S, Ojeda S, Jung H. Gene expression profiling of hypothalamic hamartomas: A search for genes associated with central precocious puberty. Horm Res 2008; 69(2): 114-23.
[http://dx.doi.org/10.1159/000111815] [PMID: 18059092]
[61]
Shimogori T, Lee DA, Miranda-Angulo A, et al. A genomic atlas of mouse hypothalamic development. Nat Neurosci 2010; 13(6): 767-75.
[http://dx.doi.org/10.1038/nn.2545] [PMID: 20436479]
[62]
Boles NC, Hirsch SE, Le S, et al. NPTX1 regulates neural lineage specification from human pluripotent stem cells. Cell Rep 2014; 6(4): 724-36.
[http://dx.doi.org/10.1016/j.celrep.2014.01.026] [PMID: 24529709]
[63]
Liu H, Kong X, Chen F. Mkrn3 functions as a novel ubiquitin E3 ligase to inhibit Nptx1 during puberty initiation. Oncotarget 2017; 8(49): 85102-9.
[http://dx.doi.org/10.18632/oncotarget.19347] [PMID: 29156706]
[64]
Liu M, Fan L, Gong CX. A novel heterozygous MKRN3 nonsense mutation in a Chinese girl with idiopathic central precocious puberty. A case report Medicine 2020; 99(38): e22295.
[http://dx.doi.org/10.1097/MD.0000000000022295] [PMID: 32957387]
[65]
Varimo T, Iivonen AP, Kansakoski J, et al. Familial central precocious puberty: Two novel MKRN3 mutations. Pediatr Res 2020.
[http://dx.doi.org/10.1111/cen.12854] [PMID: 33214675]
[66]
Abreu AP, Toro CA, Song YB, et al. MKRN3 inhibits the reproductive axis through actions in kisspeptin-expressing neurons. J Clin Invest 2020; 130(8): 4486-500.
[http://dx.doi.org/10.1172/JCI136564] [PMID: 32407292]
[67]
Fanis P, Skordis N, Toumba M, et al. Central precocious puberty caused by novel mutations in the promoter and 5′-UTR region of the imprinted MKRN3 gene. Front Endocrinol 2019; 10: 677.
[http://dx.doi.org/10.3389/fendo.2019.00677] [PMID: 31636607]
[68]
Lu W, Wang J, Li C, Sun M, Hu R, Wang W. A novel mutation in 5′-UTR of Makorin ring finger 3 gene associated with the familial precocious puberty. Acta Biochim Biophys Sin 2018; 50(12): 1291-3.
[http://dx.doi.org/10.1093/abbs/gmy124] [PMID: 30462148]
[69]
Macedo DB, França MM, Montenegro LR, et al. Central precocious puberty caused by a heterozygous deletion in the MKRN3 promoter region. Neuroendocrinology 2018; 107(2): 127-32.
[http://dx.doi.org/10.1159/000490059] [PMID: 29763903]
[70]
Simon D, Ba I, Mekhail N, et al. Mutations in the maternally imprinted gene MKRN3 are common in familial central precocious puberty. Eur J Endocrinol 2016; 174(1): 1-8.
[http://dx.doi.org/10.1530/EJE-15-0488] [PMID: 26431553]
[71]
Ortiz-Cabrera NV, Riveiro-Álvarez R, López-Martínez MÁ, et al. Clinical exome sequencing reveals MKRN3 pathogenic variants in familial and nonfamilial idiopathic central precocious puberty. Horm Res Paediatr 2017; 87(2): 88-94.
[http://dx.doi.org/10.1159/000453262] [PMID: 27931036]
[72]
Lee HS, Jin HS, Shim YS, et al. Low frequency of MKRN3 mutations in central precocious puberty among Korean girls. Horm Metab Res 2016; 48(2): 118-22.
[http://dx.doi.org/10.1055/s-0035-1548938] [PMID: 25938887]
[73]
Schreiner F, Gohlke B, Hamm M, Korsch E, Woelfle J. MKRN3 mutations in familial central precocious puberty. Horm Res Paediatr 2014; 82(2): 122-6.
[http://dx.doi.org/10.1159/000362815] [PMID: 25011910]
[74]
Simsek E, Demiral M, Ceylaner S, Kırel B. Two Frameshift Mutations in MKRN3 in Turkish Patients with Familial Central Precocious Puberty. Horm Res Paediatr 2017; 87(6): 405-11.
[http://dx.doi.org/10.1159/000450923] [PMID: 27798941]
[75]
Grandone A, Capristo C, Cirillo G, et al. Molecular screening of MKRN3, DLK1, and KCNK9 genes in girls with idiopathic central precocious puberty. Horm Res Paediatr 2017; 88(3-4): 194-200.
[http://dx.doi.org/10.1159/000477441] [PMID: 28672280]
[76]
Macedo DB, Abreu AP, Reis AC, et al. Central precocious puberty that appears to be sporadic caused by paternally inherited mutations in the imprinted gene makorin ring finger 3. J Clin Endocrinol Metab 2014; 99(6): E1097-103.
[http://dx.doi.org/10.1210/jc.2013-3126] [PMID: 24628548]
[77]
Dimitrova-Mladenova MS, Stefanova EM, Glushkova M, et al. Males with paternally inherited MKRN3 mutations may be asymptomatic. J Pediatr 2016; 179: 263-5.
[http://dx.doi.org/10.1016/j.jpeds.2016.08.065] [PMID: 27640350]
[78]
Stecchini MF, Macedo DB, Reis AC, et al. Time course of central precocious puberty development caused by an MKRN3 gene mutation: A prismatic case. Horm Res Paediatr 2016; 86(2): 126-30.
[http://dx.doi.org/10.1159/000447515] [PMID: 27424312]
[79]
Lin WD, Wang CH, Tsai FJ. Genetic screening of the makorin ring finger 3 gene in girls with idiopathic central precocious puberty. Clin Chem Lab Med 2016; 54(3): e93-6.
[http://dx.doi.org/10.1515/cclm-2015-0408] [PMID: 26402883]
[80]
Aycan Z, Savaş-Erdeve Ş, Çetinkaya S, et al. Investigation of MKRN3 mutation in patients with familial central precocious puberty. J Clin Res Pediatr Endocrinol 2018; 10(3): 223-9.
[http://dx.doi.org/10.4274/jcrpe.5506] [PMID: 29537379]
[81]
Chen T, Chen L, Wu H, et al. Low Frequency of MKRN3 and DLK1 variants in Chinese children with central precocious puberty. Int J Endocrinol 2019; 2019: 9879367.
[http://dx.doi.org/10.1155/2019/9879367] [PMID: 31687022]
[82]
Nishioka J, Shima H, Fukami M, et al. The first Japanese case of central precocious puberty with a novel MKRN3 mutation. Hum Genome Var 2017; 4(1): 17017.
[http://dx.doi.org/10.1038/hgv.2017.17] [PMID: 28546864]
[83]
Christoforidis A, Skordis N, Fanis P, et al. A novel MKRN3 nonsense mutation causing familial central precocious puberty. Endocrine 2017; 56(2): 446-9.
[http://dx.doi.org/10.1007/s12020-017-1232-6] [PMID: 28132164]
[84]
Neocleous V, Shammas C, Phelan MM, Nicolaou S, Phylactou LA, Skordis N. In silico analysis of a novel MKRN3 missense mutation in familial central precocious puberty. Clin Endocrinol 2016; 84(1): 80-4.
[http://dx.doi.org/10.1111/cen.12854] [PMID: 26173472]
[85]
Bessa DS, Macedo DB, Brito VN, et al. High frequency of MKRN3 mutations in male central precocious puberty previously classified as idiopathic. Neuroendocrinology 2017; 105(1): 17-25.
[http://dx.doi.org/10.1159/000446963] [PMID: 27225315]
[86]
Settas N, Dacou-Voutetakis C, Karantza M, Kanaka-Gantenbein C, Chrousos GP, Voutetakis A. Central precocious puberty in a girl and early puberty in her brother caused by a novel mutation in the MKRN3 gene. J Clin Endocrinol Metab 2014; 99(4): E647-51.
[http://dx.doi.org/10.1210/jc.2013-4084] [PMID: 24438377]
[87]
Känsäkoski J, Raivio T, Juul A, Tommiska J. A missense mutation in MKRN3 in a Danish girl with central precocious puberty and her brother with early puberty. Pediatr Res 2015; 78(6): 709-11.
[http://dx.doi.org/10.1038/pr.2015.159] [PMID: 26331766]
[88]
Pagani S, Calcaterra V, Acquafredda G, et al. MKRN3 and KISS1R mutations in precocious and early puberty. Ital J Pediatr 2020; 46(1): 39.
[http://dx.doi.org/10.1186/s13052-020-0808-6] [PMID: 32228714]
[89]
de Vries L, Gat-Yablonski G, Dror N, Singer A, Phillip M. A novel MKRN3 missense mutation causing familial precocious puberty. Hum Reprod 2014; 29(12): 2838-43.
[http://dx.doi.org/10.1093/humrep/deu256] [PMID: 25316453]
[90]
Soriano-Guillén L, Argente J. Central precocious puberty, functional and tumor-related. Best Pract Res Clin Endocrinol Metab 2019; 33(3): 101262.
[http://dx.doi.org/10.1016/j.beem.2019.01.003] [PMID: 30733078]
[91]
Ojeda SR, Lomniczi A. Puberty in 2013: Unravelling the mystery of puberty. Nat Rev Endocrinol 2014; 10(2): 67-9.
[http://dx.doi.org/10.1038/nrendo.2013.233] [PMID: 24275741]
[92]
Mul D, Hughes IA. The use of GnRH agonists in precocious puberty. Eur J Endocrinol 2008; 159 (Suppl. 1): S3-8.
[http://dx.doi.org/10.1530/EJE-08-0814] [PMID: 19064674]
[93]
Chen M, Eugster EA. Central precocious puberty: Update on diagnosis and treatment. Paediatr Drugs 2015; 17(4): 273-81.
[http://dx.doi.org/10.1007/s40272-015-0130-8] [PMID: 25911294]
[94]
Witchel SF, Baens-Bailon RG, Lee PA. Treatment of central precocious puberty: Comparison of urinary gonadotropin excretion and Gonadotropin-Releasing Hormone (GnRH) stimulation tests in monitoring GnRH analog therapy. J Clin Endocrinol Metab 1996; 81(4): 1353-6.
[http://dx.doi.org/10.4.86363320.1210/jcem.8] [PMID: 8636332]
[95]
Roth C. Therapeutic potential of GnRH antagonists in the treatment of precocious puberty. Expert Opin Investig Drugs 2002; 11(9): 1253-9.
[http://dx.doi.org/10.1517/13543784.11.9.1253] [PMID: 12225246]
[96]
Hirsch HJ, Gillis D, Strich D, et al. The histrelin implant: A novel treatment for central precocious puberty. Pediatrics 2005; 116(6): e798-802.
[http://dx.doi.org/10.1542/peds.2005-0538] [PMID: 16322137]
[97]
Silverman LA, Neely EK, Kletter GB, et al. Long-term continuous suppression with once-yearly histrelin subcutaneous implants for the treatment of central precocious puberty: A final report of a phase 3 multicenter trial. J Clin Endocrinol Metab 2015; 100(6): 2354-63.
[http://dx.doi.org/10.1210/jc.2014-3031] [PMID: 25803268]
[98]
Abbara A, Dhillo WS. Makorin rings the kisspeptin bell to signal pubertal initiation. J Clin Invest 2020; 130(8): 3957-60.
[http://dx.doi.org/10.1172/JCI139586] [PMID: 32687068]
[99]
Martínez-Aguayo A, Hernández MI, Beas F, et al. Treatment of central precocious puberty with triptorelin 11.25 mg depot formulation. J Pediatr Endocrinol Metab 2006; 19(8): 963-70.
[http://dx.doi.org/10.1515/JPEM.2006.19.8.963] [PMID: 16995580]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy