Skip to content
Licensed Unlicensed Requires Authentication Published by De Gruyter June 20, 2012

Estrogen receptor α gene analysis in girls with central precocious puberty

  • Hae Sang Lee , Hong Kyu Park , Kyung Hee Kim , Jung Hee Ko , You Jin Kim , Kyung Hee Yi and Jin Soon Hwang EMAIL logo

Abstract

Objective: Estrogen is the final key factor that triggers the onset of puberty. The raised sensitivity of estrogen receptor, which may be caused by an estrogen receptor α (ERα) gene mutation or polymorphism, has been implicated in the etiology of precocious puberty. The aim of this study is to identify ERα gene mutations or polymorphisms in girls with central precocious puberty (CPP).

Methods: A total of 204 Korean girls with CPP were included in this study along with 102 healthy Korean female adults as controls. All coding exons and exon-intron boundaries of the ERα gene were sequenced. The relationship between identified sequence variations and CPP were evaluated via comparison of allele frequencies between the two groups.

Results: Eight polymorphisms were identified in the ERα gene. Among the eight polymorphisms in this study, five have been previously reported, whereas the other three were novel polymorphisms. Two of the three novel polymorphisms, p.G145S in exon 1 and p.R555H in exon 8 were only identified in the patient group. The subgroup with p.G145S showed a significantly higher level of peak luteinizing hormone than the subgroup without p.G145S in girls with CPP.

Conclusion: The scanning and typing of ERα polymorphism has uncovered several potentially meaningful polymorphisms. However, no solid conclusion can be made from this study and further studies are necessary to validate the function of these polymorphisms.


Corresponding author: Jin Soon Hwang, Department of Pediatrics, Ajou University School of Medicine, San 5, Wonchon-dong, Yeongtong-gu, Suwon 443-721, Korea Phone: +82-31-219-5166, Fax: +82-31-219-5169

This study was supported by a grant from the Abbott fund.

Conflict of interest statement

Authors’ conflict of interest disclosure: None of the authors have any conflict of interest to disclose. We confirm that we have read the position of the Journal of Pediatric Endocrinology and Metabolism on the issues involved in ethical publication and affirm that this report is consistent with those guidelines.

References

1. Wheeler MD. Physical changes of puberty. Endocrinol Metab Clin North Am 1991;20:1–14.10.1016/S0889-8529(18)30279-2Search in Google Scholar

2. Papathanasiou A, Hadjiathanasiou C. Precocious puberty. Pediatr Endocrinol Rev 2006;3(Suppl 1):182–7.Search in Google Scholar

3. Teles MG, Silveira LF, Tusset C, Latronico AC. New genetic factors implicated in human GnRH-dependent precocious puberty: the role of kisspeptin system. Mol Cell Endocrinol 2011;346:84–90.10.1016/j.mce.2011.05.019Search in Google Scholar PubMed

4. Silveira LF, Teles MG, Trarbach EB, Latronico AC. Role of kisspeptin/GPR54 system in human reproductive axis. Front Horm Res 2010;39:13–24.10.1159/000312689Search in Google Scholar PubMed

5. Gianetti E, Seminara S. Kisspeptin and KISS1R: a critical pathway in the reproductive system. Reproduction 2008;136:295–301.10.1530/REP-08-0091Search in Google Scholar PubMed PubMed Central

6. Carel JC, Lahlou N, Roger M, Chaussain JL. Precocious puberty and statural growth. Hum Reprod Update 2004;10:135–47.10.1093/humupd/dmh012Search in Google Scholar PubMed

7. Roa J, Vigo E, Castellano JM, Gaytan F, Navarro VM, et al. Opposite roles of estrogen receptor (ER)-alpha and ERbeta in the modulation of luteinizing hormone responses to kisspeptin in the female rat: implications for the generation of the preovulatory surge. Endocrinology 2008;149:1627–37.10.1210/en.2007-1540Search in Google Scholar PubMed

8. Smith JT, Popa SM, Clifton DK, Hoffman GE, Steiner RA. Kiss1 neurons in the forebrain as central processors for generating the preovulatory luteinizing hormone surge. J Neurosci 2006;26:6687–94.10.1523/JNEUROSCI.1618-06.2006Search in Google Scholar PubMed PubMed Central

9. Greulich WW, Pyle SI. Radiologic atlas of skeletal development of the hand and wrist, 2nd ed. Standford, CA: Stanford University Press, 1959.10.1097/00000441-195909000-00030Search in Google Scholar

10. Moon JS, Lee SY, Nam CM, Choi JM, Choe BK, et al. 2007 Korean National Growth Charts: review of developmental process and an outlook. Korean J Pediatr 2008;51:1–25.10.3345/kjp.2008.51.1.1Search in Google Scholar

11. Carel JC, Leger J. Clinical practice. Precocious puberty. N Engl J Med 2008;358:2366–77.10.1056/NEJMcp0800459Search in Google Scholar PubMed

12. Herbison AE. Genetics of puberty. Horm Res 2007;68(Suppl 5):75–9.10.1159/000110583Search in Google Scholar

13. Herbison AE. Estrogen positive feedback to gonadotropin-releasing hormone (GnRH) neurons in the rodent: the case for the rostral periventricular area of the third ventricle (RP3V). Brain Res Rev 2008;57:277–87.10.1016/j.brainresrev.2007.05.006Search in Google Scholar

14. Naftolin F, Garcia-Segura LM, Horvath TL, Zsarnovszky A, Demir N, et al. Estrogen-induced hypothalamic synaptic plasticity and pituitary sensitization in the control of the estrogen-induced gonadotrophin surge. Reprod Sci 2007;14:101–16.10.1177/1933719107301059Search in Google Scholar

15. Greene GL, Gilna P, Waterfield M, Baker A, Hort Y, et al. Sequence and expression of human estrogen receptor complementary DNA. Science 1986;231:1150–4.10.1126/science.3753802Search in Google Scholar

16. Couse JF, Lindzey J, Grandien K, Gustafsson JA, Korach KS. Tissue distribution and quantitative analysis of estrogen receptor-alpha (ERalpha) and estrogen receptor-beta (ERbeta) messenger ribonucleic acid in the wild-type and ERalpha-knockout mouse. Endocrinology 1997;138:4613–21.10.1210/endo.138.11.5496Search in Google Scholar

17. Mayer C, Acosta-Martinez M, Dubois SL, Wolfe A, Radovick S, et al. Timing and completion of puberty in female mice depend on estrogen receptor alpha-signaling in kisspeptin neurons. Proc Natl Acad Sci USA 2010;107:22693–8.10.1073/pnas.1012406108Search in Google Scholar

18. Ponglikitmongkol M, Green S, Chambon P. Genomic organization of the human oestrogen receptor gene. EMBO J 1988;7:3385–8.10.1002/j.1460-2075.1988.tb03211.xSearch in Google Scholar

19. Kumar V, Green S, Stack G, Berry M, Jin JR, et al. Functional domains of the human estrogen receptor. Cell 1987;51: 941–51.10.1016/0092-8674(87)90581-2Search in Google Scholar

20. Metzger D, Ali S, Bornert JM, Chambon P. Characterization of the amino-terminal transcriptional activation function of the human estrogen receptor in animal and yeast cells. J Biol Chem 1995;270:9535–42.10.1074/jbc.270.16.9535Search in Google Scholar PubMed

Received: 2012-3-8
Accepted: 2012-4-27
Published Online: 2012-06-20
Published in Print: 2013-08-01

©2013 by Walter de Gruyter Berlin Boston

Downloaded on 29.3.2024 from https://www.degruyter.com/document/doi/10.1515/jpem-2012-0069/html
Scroll to top button