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An evaluation of G-protein coupled membrane estrogen receptor-1 level in stuttering

  • Laryngology
  • Published:
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Abstract

Objective

Stuttering is a widespread but little understood disease. There has been a recent increase in neuropathophysiological, genetic, and biochemical studies related to the etiopathogenesis. As developmental stuttering continues in adult males, hormonal factors are thought to have an effect. In this study, an evaluation was made for the first time of serum GPER-1 level in patients with a stutter.

Study design

Prospective case control.

Materials and methods

The study included 30 patients with a stutter, aged < 18 years, and 35 age-matched children as the control group. The Stuttering Severity Instrument-3 form was administered to the patients. Evaluations were made of serum GPER-1, TSH, estradiol, prolactin, and progesterone and testosterone levels.

Results

GPER-1 level was determined as 0.51 (0.42–0.67) ng/mL in the patients and as 0.19 (0.13–0.25) ng/mL in the control group, and the difference was statistically significant (p < 0.001). A statistically significant difference was determined between genders with GPER-1 level of 0.56 (0.44–0.68) ng/mL in the male stuttering patient group and 0.44 (0.35–0.49) ng/mL in the female patient group (p = 0.026). Differential diagnosis with ROC analysis for the serum GPER-1 levels was statistically significant [Area under the ROC curve (AUC): 0.998, confidence interval, CI 0.992-1.000, p < 0.001].

Conclusion

The GPER-1 levels of the stuttering patients were found to be higher than those of the control group and GPER-1 levels of male patients were higher than those of females. As GPER-1 has high sensitivity and sensitivity, it could be considered important in the diagnosis and treatment of stuttering.

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References

  1. Meyer MR, Clegg DJ, Prossnitz ER, Barton M (2011) Obesity, insulin resistanceand diabetes: sex differences and role of oestrogen receptors. Acta Physiol 203:259–269

    Article  CAS  Google Scholar 

  2. Meyer MR, Prossnitz ER, Barton M(2011) The G protein-coupled estrogenreceptor GPER/GPR30 as a regulator of cardiovascular function. Vasc Pharmacol 55: 17–25

    Article  CAS  Google Scholar 

  3. Turgeon JL, McDonnell DP, Martin KA, Wise PM (2004) Hormone therapy: physiological complexity belies therapeutic simplicity. Science 304: 1269–1273

    Article  CAS  PubMed  Google Scholar 

  4. Tiano JP, Mauvais-Jarvis F (2012) Importance of oestrogen receptors to preserv functional beta-cell mass in diabetes. Nat Rev Endocrinol 8:342–351

    Article  CAS  PubMed  Google Scholar 

  5. Barton M (2013) Cholesterol and atherosclerosis: modulation by oestrogen. Curr Opin Lipidol 24:214–220

    Article  CAS  PubMed  Google Scholar 

  6. Deroo BJ, Korach KS (2006) Estrogen receptors and human disease. J Clin Invest 116:561–570

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Barton M (2012) Position paper: the membrane estrogen receptor GPER—clues and questions. Steroids 77:935–942

    Article  CAS  PubMed  Google Scholar 

  8. Filardo EJ, Thomas P (2012) Minireview: G protein-coupled estrogen receptor-1, GPER-1: its mechanism of action and role in female reproductive cancer, renal and vascular physiology. Endocrinology 153:2953–2962

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Otto C, Fuchs I, Kauselmann G, Kern H, Zevnik B, Andreasen P et al (2009) GPR30 does not mediate estrogenic responses in reproductive organs in mice. Biol Reprod 80:34–41

    Article  CAS  PubMed  Google Scholar 

  10. Mizukami Y (2010) In vivo functions of GPR30/GPER-1, a membrane receptor for estrogen: from discovery to functions in vivo. Endocr J 57:101–107

    Article  CAS  PubMed  Google Scholar 

  11. Han G, Li F, Yu X, White RE (2013) GPER: a novel target for non-genomic estrogen action in the cardiovascular system. Pharmacol Res 71:53–60

    Article  CAS  PubMed  Google Scholar 

  12. Stygar D, Westlund P, Eriksson H, Sahlin L (2006) Identification of wild type and variants of oestrogen receptors in polymorphonuclear and mononuclear leucocytes. Clin Endocrinol 64:74–81

    Article  CAS  Google Scholar 

  13. Revankar CM, Cimino DF, Sklar LA, Arterburn JB, Prossnitz ER (2005) A transmembrane intracellular estrogen receptor mediates rapid cell signaling. Science 307:1625–1630

    Article  CAS  PubMed  Google Scholar 

  14. Sanden C, Broselid S, Cornmark L, Andersson K, Daszkiewicz-Nilsson J, Mårtensson UE et al (2011) G proteincoupled estrogen receptor 1/G protein-coupled receptor 30 localizes in the plasma membrane and traffics intracellularly on cytokeratin intermediate filaments. Mol Pharmacol 79:400–410

    Article  CAS  PubMed  Google Scholar 

  15. Findikli E, Camkurt MA, Karaaslan MF, Kurutas EB, Altun H, İzci F et al (2016) Serum levels of G protein-coupled estrogen receptor 1(GPER-1) in drug-naive patients with generalized anxiety disorder. Psychiatry Res 244:312–316

    Article  Google Scholar 

  16. Altun H, Kurutas EB, Sahin N, Sinir H, Findikli E (2017) Decreased levels of G protein-coupled estrogen receptor in children with autism spectrum disorders. Psychiatry Res 257:67–71

    Article  CAS  PubMed  Google Scholar 

  17. Yairi E, Ambrose N (1992) Onset of stuttering in preschool children: selected factors. J Speech Hear Res 35:782–788

    Article  CAS  PubMed  Google Scholar 

  18. Bloodstein O (1995) A handbook on stuttering. Easter Seal Society, Chicago

    Google Scholar 

  19. Pesak J, Opavsky J (2000) Decreased copper level in the blood serum of male stutterers and the occurrence of the vibratio brevis phenomenon. Biomed Pap 143: 71–74

    Google Scholar 

  20. Andrews G, Harris M (1964) The syndrome of stuttering. Clinics in developmental medicine. 17. Spastics Society Medical Education and Information Unit in association with Wm. Heineman Medical Books, London

    Google Scholar 

  21. Mansson H (2000) Childhood stuttering: Incidence and development. J Fluen Disord 25:47–57

    Article  Google Scholar 

  22. Ntouroua K, Conturea EG, Walden TA (2013) Emotional reactivity and regulation in preschool-age children who stutter. J Fluen Disord 38:260–74

    Article  Google Scholar 

  23. Yairi E, Ambrose N (2013) Epidemiology of stuttering: 21st century advances. J Fluen Disord 38:66–87. (epub 2012 Nov 27)

    Article  Google Scholar 

  24. Perez RH, Stoeckle JH (2016) Stuttering: clinical and research update. Can Fam Phys 62:479 – 84

  25. Selcuk EB, Erbay LG, Ozcan OO, Kartalcı S, Batcıoğlu K (2015) Testesterone levels of children with a diagnosis of developmental stuttering. Ther Clin Risk Manag 11;793–798

  26. American Psychiatric Association (2000). Diagnostic and statistical manual of mental disorders: DSM-IV-R, 4th edn. American Psychiatric Association, Washington, DC

    Google Scholar 

  27. Chang SE (2014) Research updates in neuroimaging studies of children who stutter. Semin Speech Lang 35(2):67–79

    Article  PubMed  PubMed Central  Google Scholar 

  28. Sommer M, Koch MA, Paulus W, Weiller C, Bu chel C (2002) Disconnection of speech-relevant brain areas in persistent developmental stuttering. Lancet 360:380–383

    Article  PubMed  Google Scholar 

  29. Bilal N, Sarica S, Kurutas EB, Findikli E, Orhan İ, Öner E et al (2017) An evaluation of oxidative and nitrosative stres in children-who-stutter and its relationship to severity. Int J Pediatr Otorhinolaryngol 99:17–23

    Article  PubMed  Google Scholar 

  30. Ludo M, Guenther FH, Gracco VL, Ghosh SS, Wallace ME (2004) Unstable or insufficiently activated internal models and feedback-biased motor control as sources of dysfluency: a theoretical model of stuttering. Contemp Issues Commun Sci Disord 31:105–22

    Google Scholar 

  31. Wu JC, Maguire G, Riley G, Lee A, Keator D, Tang C et al (1997) Increased dopamine activity associated with stuttering. Neuroreport 8(3): 767–70

    Article  Google Scholar 

  32. Kurt AH, Tiftik RN, Un I, Ulker S, Buyukafsar K (2013) G protein-coupled estrogen receptor1 (GPER1) may mediate Rho-kinase (ROCK-2) up-regulation in coronary endothelial cells. Endocr Regul 47:75–84

    Article  CAS  PubMed  Google Scholar 

  33. Suzuki S, Brown CM, Wise PM (2006) Mechanisms of neuroprotection by estrogen. Endocrine 29:209–215

    Article  CAS  PubMed  Google Scholar 

  34. Hughes ZA, Liu F, Marquis K, Muniz L, Pangalos MN, Ring RH, Whiteside GT, Brandon NJ (2009) Estrogen receptor neurobiology and its potential for translation into broad spectrum therapeutics for CNS disorders. Curr Mol Pharm 2:215–236

    Article  CAS  Google Scholar 

  35. Xu H, Qin S, Carrasco GA, Dai Y, Filardo EJ, Prossnitz ER et al (2009) Extra-nuclear estrogen receptor GPR 30 regulates serotonin function in rat hypothalamus. Neuroscience 158:1599–1607

    Article  CAS  PubMed  Google Scholar 

  36. Hazell GG, Yao ST, Roper JA, Prossnitz ER, O’Carroll AM, Lolait SJ (2009) Localisation of GPR30, a novel G protein-coupled oestrogen receptor, suggests multiple functions in rodent brain and peripheral tissues. J Endocrinol 202:223–236

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Tian Z, Wang Y, Zhang N, Guo Y, Feng B, Liu S, Zhao M (2013) Estrogen receptor GPR30 exerts anxiolytic effects by maintaining the balance between GABAergican dglutamatergic transmission in the basolateral amygdala of ovariectomized mice after stress. Psychoneuroendocrinology 38:2218–2233

    Article  CAS  PubMed  Google Scholar 

  38. Hammond R, Gibbs RB (2011) GPR30 is positioned to mediate estrogen effects on basal forebrain cholinergic neurons and cognitive performance. BrainRes 1379:53–60

    CAS  Google Scholar 

  39. İbiloğlu AO (2011) Stuttering. Current approaches in psychiatry 3:704–727. https://doi.org/10.5455/cap.20110332

    Google Scholar 

  40. Kızıltan G, Akalın MA (1996) Stuttering may be a type of action dystonia. Mov Disord 11: 278–282

    Google Scholar 

  41. Alm PA (2005) Copper in developmental stuttering. Folia Phoniatr Logop 57: 216–222

    Article  Google Scholar 

  42. Bloodstein O (1993) Stuttering: the search for a cause and cure. Allyn & Bacon, Boston

    Google Scholar 

  43. Kurt AH, Buyukafsar K (2013) Vasoconstriction induced by G1, a G-protein-coupled oestrogen receptor1 (GPER-1) agonist, in the isolated perfused rat kidney. Eur J Pharmacol 702:71–78

    Article  CAS  PubMed  Google Scholar 

  44. Altun I, Kurutas EB (2015) G Protein–coupled estrogen receptor levels after peripheral nerve injury in an experimental rat model. World Neurosurg 84:1903–1906

    Article  PubMed  Google Scholar 

Download references

Funding

This study was supported by the Scientific Research Projects Unit of Kahramanmaras Sutcu Imam University (Project no: 2016/3–56 M).

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Correspondence to Nagihan Bilal.

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This manuscript has not been published and has been submitted only to European Archives Oto-rhino-laryngology. All the authors have read the manuscript and have approved this submission. The authors report no conflicts of interest.

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Bilal, N., Kurutas, E.B. & Orhan, I. An evaluation of G-protein coupled membrane estrogen receptor-1 level in stuttering. Eur Arch Otorhinolaryngol 275, 469–476 (2018). https://doi.org/10.1007/s00405-017-4862-7

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  • DOI: https://doi.org/10.1007/s00405-017-4862-7

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