Skip to main content
Top
Published in: European Archives of Oto-Rhino-Laryngology 2/2018

01-02-2018 | Laryngology

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

Authors: Nagihan Bilal, Ergül Belge Kurutas, Israfil Orhan

Published in: European Archives of Oto-Rhino-Laryngology | Issue 2/2018

Login to get access

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.
Literature
1.
go back to reference Meyer MR, Clegg DJ, Prossnitz ER, Barton M (2011) Obesity, insulin resistanceand diabetes: sex differences and role of oestrogen receptors. Acta Physiol 203:259–269CrossRef Meyer MR, Clegg DJ, Prossnitz ER, Barton M (2011) Obesity, insulin resistanceand diabetes: sex differences and role of oestrogen receptors. Acta Physiol 203:259–269CrossRef
2.
go back to reference Meyer MR, Prossnitz ER, Barton M(2011) The G protein-coupled estrogenreceptor GPER/GPR30 as a regulator of cardiovascular function. Vasc Pharmacol 55: 17–25CrossRef Meyer MR, Prossnitz ER, Barton M(2011) The G protein-coupled estrogenreceptor GPER/GPR30 as a regulator of cardiovascular function. Vasc Pharmacol 55: 17–25CrossRef
3.
go back to reference Turgeon JL, McDonnell DP, Martin KA, Wise PM (2004) Hormone therapy: physiological complexity belies therapeutic simplicity. Science 304: 1269–1273CrossRefPubMed Turgeon JL, McDonnell DP, Martin KA, Wise PM (2004) Hormone therapy: physiological complexity belies therapeutic simplicity. Science 304: 1269–1273CrossRefPubMed
4.
go back to reference Tiano JP, Mauvais-Jarvis F (2012) Importance of oestrogen receptors to preserv functional beta-cell mass in diabetes. Nat Rev Endocrinol 8:342–351CrossRefPubMed Tiano JP, Mauvais-Jarvis F (2012) Importance of oestrogen receptors to preserv functional beta-cell mass in diabetes. Nat Rev Endocrinol 8:342–351CrossRefPubMed
5.
go back to reference Barton M (2013) Cholesterol and atherosclerosis: modulation by oestrogen. Curr Opin Lipidol 24:214–220CrossRefPubMed Barton M (2013) Cholesterol and atherosclerosis: modulation by oestrogen. Curr Opin Lipidol 24:214–220CrossRefPubMed
7.
go back to reference Barton M (2012) Position paper: the membrane estrogen receptor GPER—clues and questions. Steroids 77:935–942CrossRefPubMed Barton M (2012) Position paper: the membrane estrogen receptor GPER—clues and questions. Steroids 77:935–942CrossRefPubMed
8.
go back to reference 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 153:2953–2962CrossRefPubMedPubMedCentral 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 153:2953–2962CrossRefPubMedPubMedCentral
9.
go back to reference 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 80:34–41CrossRefPubMed 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 80:34–41CrossRefPubMed
10.
go back to reference Mizukami Y (2010) In vivo functions of GPR30/GPER-1, a membrane receptor for estrogen: from discovery to functions in vivo. Endocr J 57:101–107CrossRefPubMed Mizukami Y (2010) In vivo functions of GPR30/GPER-1, a membrane receptor for estrogen: from discovery to functions in vivo. Endocr J 57:101–107CrossRefPubMed
11.
go back to reference Han G, Li F, Yu X, White RE (2013) GPER: a novel target for non-genomic estrogen action in the cardiovascular system. Pharmacol Res 71:53–60CrossRefPubMed Han G, Li F, Yu X, White RE (2013) GPER: a novel target for non-genomic estrogen action in the cardiovascular system. Pharmacol Res 71:53–60CrossRefPubMed
12.
go back to reference 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 64:74–81CrossRef 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 64:74–81CrossRef
13.
go back to reference Revankar CM, Cimino DF, Sklar LA, Arterburn JB, Prossnitz ER (2005) A transmembrane intracellular estrogen receptor mediates rapid cell signaling. Science 307:1625–1630CrossRefPubMed Revankar CM, Cimino DF, Sklar LA, Arterburn JB, Prossnitz ER (2005) A transmembrane intracellular estrogen receptor mediates rapid cell signaling. Science 307:1625–1630CrossRefPubMed
14.
go back to reference 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 79:400–410CrossRefPubMed 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 79:400–410CrossRefPubMed
15.
go back to reference 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 244:312–316CrossRef 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 244:312–316CrossRef
16.
go back to reference 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 257:67–71CrossRefPubMed 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 257:67–71CrossRefPubMed
17.
go back to reference Yairi E, Ambrose N (1992) Onset of stuttering in preschool children: selected factors. J Speech Hear Res 35:782–788CrossRefPubMed Yairi E, Ambrose N (1992) Onset of stuttering in preschool children: selected factors. J Speech Hear Res 35:782–788CrossRefPubMed
18.
go back to reference Bloodstein O (1995) A handbook on stuttering. Easter Seal Society, Chicago Bloodstein O (1995) A handbook on stuttering. Easter Seal Society, Chicago
19.
go back to reference 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 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
20.
go back to reference 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 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
21.
go back to reference Mansson H (2000) Childhood stuttering: Incidence and development. J Fluen Disord 25:47–57CrossRef Mansson H (2000) Childhood stuttering: Incidence and development. J Fluen Disord 25:47–57CrossRef
22.
go back to reference Ntouroua K, Conturea EG, Walden TA (2013) Emotional reactivity and regulation in preschool-age children who stutter. J Fluen Disord 38:260–74CrossRef Ntouroua K, Conturea EG, Walden TA (2013) Emotional reactivity and regulation in preschool-age children who stutter. J Fluen Disord 38:260–74CrossRef
23.
go back to reference Yairi E, Ambrose N (2013) Epidemiology of stuttering: 21st century advances. J Fluen Disord 38:66–87. (epub 2012 Nov 27)CrossRef Yairi E, Ambrose N (2013) Epidemiology of stuttering: 21st century advances. J Fluen Disord 38:66–87. (epub 2012 Nov 27)CrossRef
24.
go back to reference Perez RH, Stoeckle JH (2016) Stuttering: clinical and research update. Can Fam Phys 62:479 – 84 Perez RH, Stoeckle JH (2016) Stuttering: clinical and research update. Can Fam Phys 62:479 – 84
25.
go back to reference 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 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.
go back to reference American Psychiatric Association (2000). Diagnostic and statistical manual of mental disorders: DSM-IV-R, 4th edn. American Psychiatric Association, Washington, DC American Psychiatric Association (2000). Diagnostic and statistical manual of mental disorders: DSM-IV-R, 4th edn. American Psychiatric Association, Washington, DC
28.
go back to reference Sommer M, Koch MA, Paulus W, Weiller C, Bu chel C (2002) Disconnection of speech-relevant brain areas in persistent developmental stuttering. Lancet 360:380–383CrossRefPubMed Sommer M, Koch MA, Paulus W, Weiller C, Bu chel C (2002) Disconnection of speech-relevant brain areas in persistent developmental stuttering. Lancet 360:380–383CrossRefPubMed
29.
go back to reference 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 99:17–23CrossRefPubMed 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 99:17–23CrossRefPubMed
30.
go back to reference 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 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
31.
go back to reference Wu JC, Maguire G, Riley G, Lee A, Keator D, Tang C et al (1997) Increased dopamine activity associated with stuttering. Neuroreport 8(3): 767–70CrossRef Wu JC, Maguire G, Riley G, Lee A, Keator D, Tang C et al (1997) Increased dopamine activity associated with stuttering. Neuroreport 8(3): 767–70CrossRef
32.
go back to reference 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 47:75–84CrossRefPubMed 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 47:75–84CrossRefPubMed
33.
go back to reference Suzuki S, Brown CM, Wise PM (2006) Mechanisms of neuroprotection by estrogen. Endocrine 29:209–215CrossRefPubMed Suzuki S, Brown CM, Wise PM (2006) Mechanisms of neuroprotection by estrogen. Endocrine 29:209–215CrossRefPubMed
34.
go back to reference 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 2:215–236CrossRef 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 2:215–236CrossRef
35.
go back to reference 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 158:1599–1607CrossRefPubMed 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 158:1599–1607CrossRefPubMed
36.
go back to reference 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 202:223–236CrossRefPubMedPubMedCentral 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 202:223–236CrossRefPubMedPubMedCentral
37.
go back to reference 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 38:2218–2233CrossRefPubMed 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 38:2218–2233CrossRefPubMed
38.
go back to reference Hammond R, Gibbs RB (2011) GPR30 is positioned to mediate estrogen effects on basal forebrain cholinergic neurons and cognitive performance. BrainRes 1379:53–60 Hammond R, Gibbs RB (2011) GPR30 is positioned to mediate estrogen effects on basal forebrain cholinergic neurons and cognitive performance. BrainRes 1379:53–60
40.
go back to reference Kızıltan G, Akalın MA (1996) Stuttering may be a type of action dystonia. Mov Disord 11: 278–282 Kızıltan G, Akalın MA (1996) Stuttering may be a type of action dystonia. Mov Disord 11: 278–282
41.
go back to reference Alm PA (2005) Copper in developmental stuttering. Folia Phoniatr Logop 57: 216–222CrossRef Alm PA (2005) Copper in developmental stuttering. Folia Phoniatr Logop 57: 216–222CrossRef
42.
go back to reference Bloodstein O (1993) Stuttering: the search for a cause and cure. Allyn & Bacon, Boston Bloodstein O (1993) Stuttering: the search for a cause and cure. Allyn & Bacon, Boston
43.
go back to reference 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 702:71–78CrossRefPubMed 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 702:71–78CrossRefPubMed
44.
go back to reference Altun I, Kurutas EB (2015) G Protein–coupled estrogen receptor levels after peripheral nerve injury in an experimental rat model. World Neurosurg 84:1903–1906CrossRefPubMed Altun I, Kurutas EB (2015) G Protein–coupled estrogen receptor levels after peripheral nerve injury in an experimental rat model. World Neurosurg 84:1903–1906CrossRefPubMed
Metadata
Title
An evaluation of G-protein coupled membrane estrogen receptor-1 level in stuttering
Authors
Nagihan Bilal
Ergül Belge Kurutas
Israfil Orhan
Publication date
01-02-2018
Publisher
Springer Berlin Heidelberg
Published in
European Archives of Oto-Rhino-Laryngology / Issue 2/2018
Print ISSN: 0937-4477
Electronic ISSN: 1434-4726
DOI
https://doi.org/10.1007/s00405-017-4862-7

Other articles of this Issue 2/2018

European Archives of Oto-Rhino-Laryngology 2/2018 Go to the issue