The Role of Genetics in Central Precocious Puberty: Confirmed and Potential Neuroendocrine Genetic and Epigenetic Contributors and Their Interactions with Endocrine Disrupting Chemicals (EDCs)

Andrea Mucci; Ethel Clemente

doi:10.3390/endocrines3030035

journal article Open Access Jul 25, 2022

The Role of Genetics in Central Precocious Puberty: Confirmed and Potential Neuroendocrine Genetic and Epigenetic Contributors and Their Interactions with Endocrine Disrupting Chemicals (EDCs)

Andrea Mucci Ethel Clemente

Endocrines Vol. 3 No. 3 pp. 433-451 · MDPI AG

View at Publisher Save 10.3390/endocrines3030035

Abstract

Despite the growing prevalence of central precocious puberty (CPP), most cases are still diagnosed as “idiopathic” due to the lack of identifiable findings of other diagnostic etiology. We are gaining greater insight into some key genes affecting neurotransmitters and receptors and how they stimulate or inhibit gonadotropin-releasing hormone (GnRH) secretion, as well as transcriptional and epigenetic influences. Although the genetic contributions to pubertal regulation are more established in the hypogonadotropic hypogonadism (HH) literature, cases of CPP have provided the opportunity to learn more about its own genetic influences. There have been clinically confirmed cases of CPP associated with gene mutations in kisspeptin and its receptor (KISS1, KISS1R), Delta-like noncanonical Notch ligand 1 (DLK1), and the now most commonly identified genetic cause of CPP, makorin ring finger protein (MKRN3). In addition to these proven genetic causes, a number of other candidates continue to be evaluated. After reviewing the basic clinical aspects of puberty, we summarize what is known about the various genetic and epigenetic causes of CPP as well as discuss some of the potential effects of endocrine disrupting chemicals (EDCs) on some of these processes.

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References

141

[1]

Sperling, M., Majzoub, J.A., Menon, R.K., and Stratakis, C.A. (2021). Puberty in the Female and Its Disorders. Sperling Pediatric Endocrinology, Elsevier Inc.. [5th ed.].

[2]

Sperling, M., Majzoub, J.A., Menon, R.K., and Stratakis, C.A. (2021). Puberty and Its Disorders in the Male, Elsevier Inc.. [5th ed].

[3]

Marshall "Variations in pattern of pubertal changes in girls" Obstet. Gynecol. Surv. (1969)

[4]

Marshall "Variations in the Pattern of Pubertal Changes in Boys" Arch. Dis. Child. (1970) 10.1136/adc.45.239.13

[5]

Busch "Trends in the Incidence of Central Precocious Puberty and Normal Variant Puberty Among Children in Denmark, 1998 to 2017" JAMA Netw. Open (2020) 10.1001/jamanetworkopen.2020.15665

[6]

Teilmann "Prevalence and incidence of precocious pubertal development in Denmark: An epidemiologic study based on national registries" Pediatrics (2005) 10.1542/peds.2005-0012

[7]

Corripio "Central precocious puberty in children living in Spain: Incidence, prevalence, and influence of adoption and immigration" J. Clin. Endocrinol. Metab. (2010) 10.1210/jc.2010-1025

[8]

Rigou "Marked geographic patterns in the incidence of idiopathic central precocious puberty: A nationwide study in France" Eur. J. Endocrinol. (2018) 10.1530/eje-17-0379

[9]

Kim, S.H., Huh, K., Won, S., Lee, K.W., and Park, M.J. (2015). A Significant Increase in the Incidence of Central Precocious Puberty among Korean Girls from 2004 to 2010. PLoS ONE, 10. 10.1371/journal.pone.0141844

[10]

Kim "Incidence and Prevalence of Central Precocious Puberty in Korea: An Epidemiologic Study Based on a National Database" J. Pediatr. (2019) 10.1016/j.jpeds.2018.12.022

[11]

Franssen "Endocrine-disrupting chemicals and their effects on puberty" Best Pract. Res. Clin. Endocrinol. Metab. (2021)

[12]

Spaziani "Hypothalamo-Pituitary axis and puberty" Mol. Cell. Endocrinol. (2021) 10.1016/j.mce.2020.111094

[13]

Erkekoglu "The evaluation of possible role of endocrine disruptors in central and peripheral precocious puberty" Toxicol. Mech. Methods (2016) 10.3109/15376516.2016.1158894

[14]

Rattan "The epigenetic impacts of endocrine disruptors on female reproduction across generations" Biol. Reprod. (2019) 10.1093/biolre/ioz081

[15]

Butz "Molecular genetic diagnostics of hypogonadotropic hypogonadism: From panel design towards result interpretation in clinical practice" Hum. Genet. (2021) 10.1007/s00439-020-02148-0

[16]

Zhu "Genetics of pubertal timing" Curr. Opin. Pediatr. (2018) 10.1097/mop.0000000000000642

[17]

Roberts "Genetics in endocrinology genetic etiologies of central precocious puberty and the role of imprinted genes" Eur. J. Endocrinol. (2020) 10.1530/eje-20-0103

[18]

Aguirre "Central precocious puberty: From genetics to treatment" Best Pract. Res. Clin. Endocrinol. Metab. (2018) 10.1016/j.beem.2018.05.008

[19]

Manotas "Genetic and Epigenetic Control of Puberty" Sex. Dev. (2021) 10.1159/000519039

[20]

Sankilampi "Activation of the hypothalamic-pituitary-gonadal axis in infancy: Minipuberty" Horm. Res. Paediatr. (2014) 10.1159/000362414

[21]

Schmidt "Serum concentrations of LH and FSH in the healthy newborn" Eur. J. Endocrinol. (2000) 10.1530/eje.0.1430213

[22]

Toro "Hypothalamic epigenetics driving female puberty" J. Neuroendocrinol. (2018) 10.1111/jne.12589

[23]

Role of KNDy Neurons Expressing Kisspeptin, Neurokinin B, and Dynorphin A as a GnRH Pulse Generator Controlling Mammalian Reproduction

Yoshihisa Uenoyama, Mayuko Nagae, Hitomi Tsuchida et al.

Frontiers in Endocrinology 2021 10.3389/fendo.2021.724632

[24]

Lebrethon "In vitro stimulation of the prepubertal rat gonadotropin-releasing hormone pulse generator by leptin and neuropeptide Y through distinct mechanisms" Endocrinology (2000) 10.1210/endo.141.4.7432

[25]

Slora "Secondary sexual characteristics and menses in young girls seen in office practice: A study from the pediatric research in office settings network" Pediatrics (1997) 10.1542/peds.99.4.505

[26]

Biro "Pubertal assessment method and baseline characteristics in a mixed longitudinal study of girls" Pediatrics (2010) 10.1542/peds.2009-3079

[27]

Huang "Connections between obesity and puberty" Curr. Opin. Endocr. Metab. Res. (2020) 10.1016/j.coemr.2020.08.004

[28]

Mouritsen "Recent secular trends in pubertal timing: Implications for evaluation and diagnosis of precocious puberty" Horm. Res. Paediatr. (2012) 10.1159/000336325

[29]

Houk "Adequacy of a single unstimulated luteinizing hormone level to diagnose central precocious puberty in girls" Pediatrics (2009) 10.1542/peds.2008-1180

[30]

Mucaria "Central Precocious Puberty in Boys and Girls: Similarities and Differences" Sexes (2021) 10.3390/sexes2010010

[31]

Ibanez "Use of leuprolide acetate response patterns in the early diagnosis of pubertal disorders: Comparison with the gonadotropin-releasing hormone test" J. Clin. Endocrinol. Metab. (1994)

[32]

Latronico "Causes, diagnosis, and treatment of central precocious puberty" Lancet Diabetes Endocrinol. (2016) 10.1016/s2213-8587(15)00380-0

[33]

Talarico "The role of pelvic ultrasound for the diagnosis and management of central precocious puberty: An update" Acta Biomed. (2021)

[34]

Badouraki "Evaluation of pelvic ultrasonography in the diagnosis and differentiation of various forms of sexual precocity in girls" Ultrasound Obstet. Gynecol. (2008) 10.1002/uog.6148

[35]

Kaplowitz "Earlier onset of puberty in girls: Relation to increased body mass index and race" Pediatrics (2001) 10.1542/peds.108.2.347

[36]

Carel "Consensus statement on the use of gonadotropin-releasing hormone analogs in children" Pediatrics (2009) 10.1542/peds.2008-1783

[37]

Garb "Prevalence of cranial MRI findings in girls with central precocious puberty: A systematic review and meta-analysis" J. Pediatr. Endocrinol. Metab. (2018) 10.1515/jpem-2018-0052

[38]

Klein "Phase 3 trial of a small-volume subcutaneous 6-month duration leuprolide acetate treatment for central precocious puberty" J. Clin. Endocrinol. Metab. (2020) 10.1210/clinem/dgaa479

[39]

Hirsch "The histrelin implant: A novel treatment for central precocious puberty" Pediatrics (2005) 10.1542/peds.2005-0538

[40]

Lewis "A single histrelin implant is effective for 2 years for treatment of central precocious puberty" J. Pediatr. (2013) 10.1016/j.jpeds.2013.05.033

[41]

Lazar "Growth pattern and final height after cessation of gonadotropin-suppressive therapy in girls with central sexual precocity" J. Clin. Endocrinol. Metab. (2007) 10.1210/jc.2007-0321

[42]

Pasquino "Long-term observation of 87 girls with idiopathic central precocious puberty treated with gonadotropin-releasing hormone analogs: Impact on adult height, body mass index, bone mineral content, and reproductive function" J. Clin. Endocrinol. Metab. (2008) 10.1210/jc.2007-1216

[43]

Paul "Long Term Effect of Gonadotropin-Releasing on Final and Near-Final Age of Less Than 5 Years" J. Clin. Endocrinol. Metab. (1995)

[44]

Lagrou "Longitudinal study of behavioral and affective patterns in girls with central precocious puberty during long-acting triptorelin therapy" Acta Paediatr. Int. J. Paediatr. (1997) 10.1111/j.1651-2227.1997.tb08602.x

[45]

Schoelwer "One-Year Follow-Up of Girls with Precocious Puberty and Their Mothers: Do Psychological Assessments Change over Time or with Treatment?" Horm. Res. Paediatr. (2017) 10.1159/000479688

[46]

Luo "Long-term efficacy and safety of gonadotropin-releasing hormone analog treatment in children with idiopathic central precocious puberty: A systematic review and meta-analysis" Clin. Endocrinol. (2021) 10.1111/cen.14410

[47]

Ke "Understanding the functions of kisspeptin and kisspeptin receptor (Kiss1R) from clinical case studies" Peptides (2019) 10.1016/j.peptides.2018.09.007

[48]

Pinilla "Kisspeptins and reproduction: Physiological roles and regulatory mechanisms" Physiol. Rev. (2012) 10.1152/physrev.00037.2010

[49]

Bhattacharya "Kisspeptin: Beyond the brain" Endocrinology (2015) 10.1210/en.2014-1915

[50]

Martin "Leptin-responsive GABAergic neurons regulate fertility through pathways that result in reduced kisspeptinergic tone" J. Neurosci. (2014) 10.1523/jneurosci.3003-13.2014

Showing 50 of 141 references

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Details

Published: Jul 25, 2022
Vol/Issue: 3(3)
Pages: 433-451
License: View

Authors

A

Andrea Mucci

Department of Pediatric Endocrinology, Cleveland Clinic Children’s Hospital, 9500 Euclid Ave. R3, Cleveland, OH 44106, USA

E

Ethel Clemente

Department of Pediatric Endocrinology, Valley Children’s Healthcare, 9300 Valley Children’s Place, Madera, CA 93636, USA

Cite This Article

Andrea Mucci, Ethel Clemente (2022). The Role of Genetics in Central Precocious Puberty: Confirmed and Potential Neuroendocrine Genetic and Epigenetic Contributors and Their Interactions with Endocrine Disrupting Chemicals (EDCs). Endocrines, 3(3), 433-451. https://doi.org/10.3390/endocrines3030035

The Role of Genetics in Central Precocious Puberty: Confirmed and Potential Neuroendocrine Genetic and Epigenetic Contributors and Their Interactions with Endocrine Disrupting Chemicals (EDCs)

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