open access

Vol 88, No 10 (2017)
Research paper
Published online: 2017-10-31
Get Citation

Increased serum neuregulin 4 levels in women with polycystic ovary syndrome: A case-control study

Muzaffer Temur1, Mehmet Calan, Murat Akşit, Özgür Yılmaz, Tayfur Çift, Burak Akselim, Burcu Dinçgez Çakmak, Emin Üstünyurt
·
Pubmed: 29192411
·
Ginekol Pol 2017;88(10):517-522.
Affiliations
  1. Bursa Yüksek İhtisas Training and Researh Hospital Department of Obstetrics and Gynecology

open access

Vol 88, No 10 (2017)
ORIGINAL PAPERS Gynecology
Published online: 2017-10-31

Abstract

Neuregulin 4 (NRG4) is an adipokine that is synthesized in many tissues and has been shown to be associated with the development of obesity and metabolic disorders in animals and humans. The aim of this study is to investigate the relationship between serum NRG4 levels and various metabolic parameters in women with PCOS. This cross-sectional study included 40 women with PCOS and 40 age- and BMI-matched controls without PCOS. NRG4, fasting blood glucose (FBG), insulin, hs-CRP, LDL-C, HDL-C, SHBG, DHEA-SO4 and total-testosterone levels were measured in all the participants. HOMA-IR was used to calculate the insulin resistance. Serum NRG4 levels were higher in women with PCOS than in healthy women (24.89 ± 9.32 [ng/mL] vs. 18.98 ± 6.40 [ng/mL], p = 0.002). FBG, LDL-C, HDL-C, LH, SHBG, FAI, DHEA-SO4, insulin, hs-CRP, HOMA-IR and total-testosterone levels were significantly higher in women with PCOS than controls. Circulating NRG4 levels were positively correlated with HOMA-IR, insulin and hs-CRP for both groups. There was a positive correlation between NRG4 and FBG in the PCOS group. HOMA-IR and hs-CRP were associated with NRG4. The high concentration of circulating NRG4 in PCOS may be associated with insulin resistance and low-grade chronic inflammation.

Abstract

Neuregulin 4 (NRG4) is an adipokine that is synthesized in many tissues and has been shown to be associated with the development of obesity and metabolic disorders in animals and humans. The aim of this study is to investigate the relationship between serum NRG4 levels and various metabolic parameters in women with PCOS. This cross-sectional study included 40 women with PCOS and 40 age- and BMI-matched controls without PCOS. NRG4, fasting blood glucose (FBG), insulin, hs-CRP, LDL-C, HDL-C, SHBG, DHEA-SO4 and total-testosterone levels were measured in all the participants. HOMA-IR was used to calculate the insulin resistance. Serum NRG4 levels were higher in women with PCOS than in healthy women (24.89 ± 9.32 [ng/mL] vs. 18.98 ± 6.40 [ng/mL], p = 0.002). FBG, LDL-C, HDL-C, LH, SHBG, FAI, DHEA-SO4, insulin, hs-CRP, HOMA-IR and total-testosterone levels were significantly higher in women with PCOS than controls. Circulating NRG4 levels were positively correlated with HOMA-IR, insulin and hs-CRP for both groups. There was a positive correlation between NRG4 and FBG in the PCOS group. HOMA-IR and hs-CRP were associated with NRG4. The high concentration of circulating NRG4 in PCOS may be associated with insulin resistance and low-grade chronic inflammation.

Get Citation

Keywords

neuregulin 4, PCOS, hs-CRP, HOMA-IR

About this article
Title

Increased serum neuregulin 4 levels in women with polycystic ovary syndrome: A case-control study

Journal

Ginekologia Polska

Issue

Vol 88, No 10 (2017)

Article type

Research paper

Pages

517-522

Published online

2017-10-31

Page views

3394

Article views/downloads

1923

DOI

10.5603/GP.a2017.0095

Pubmed

29192411

Bibliographic record

Ginekol Pol 2017;88(10):517-522.

Keywords

neuregulin 4
PCOS
hs-CRP
HOMA-IR

Authors

Muzaffer Temur
Mehmet Calan
Murat Akşit
Özgür Yılmaz
Tayfur Çift
Burak Akselim
Burcu Dinçgez Çakmak
Emin Üstünyurt

References (28)
  1. Legro RS, Arslanian SA, Ehrmann DA, et al. Endocrine Society. Diagnosis and treatment of polycystic ovary syndrome: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2013; 98(12): 4565–4592.
  2. Jayasena CN, Franks S. The management of patients with polycystic ovary syndrome. Nat Rev Endocrinol. 2014; 10(10): 624–636.
  3. Ehrmann DA. Polycystic ovary syndrome. N Engl J Med. 2005; 352(12): 1223–1236.
  4. Azziz R, Woods KS, Reyna R, et al. The prevalence and features of the polycystic ovary syndrome in an unselected population. J Clin Endocrinol Metab. 2004; 89(6): 2745–2749.
  5. Goodarzi MO, Dumesic DA, Chazenbalk G, et al. Polycystic ovary syndrome: etiology, pathogenesis and diagnosis. Nat Rev Endocrinol. 2011; 7(4): 219–231.
  6. Mani H, Levy MJ, Davies MJ, et al. Diabetes and cardiovascular events in women with polycystic ovary syndrome: a 20-year retrospective cohort study. Clin Endocrinol (Oxf). 2013; 78(6): 926–934.
  7. Tarkun I, Arslan BC, Cantürk Z, et al. Endothelial dysfunction in young women with polycystic ovary syndrome: relationship with insulin resistance and low-grade chronic inflammation. J Clin Endocrinol Metab. 2004; 89(11): 5592–5596.
  8. Demir B, Cengiz H, Ungan I, et al. The relationship between epicardial adipose tissue thickness and oxidative stress parameters in patients with isolated polycystic ovary syndrome. Gynecol Endocrinol. 2015; 31(7): 531–535.
  9. Harari D, Tzahar E, Romano J, et al. Neuregulin-4: a novel growth factor that acts through the ErbB-4 receptor tyrosine kinase. Oncogene. 1999; 18(17): 2681–2689.
  10. Britsch S. The neuregulin-I/ErbB signaling system in development and disease. Adv Anat Embryol Cell Biol. 2007; 190: 1–65.
  11. Wang GX, Zhao XY, Lin JD. The brown fat secretome: metabolic functions beyond thermogenesis. Trends Endocrinol Metab. 2015; 26(5): 231–237.
  12. Wang GX, Zhao XY, Meng ZX, et al. The brown fat-enriched secreted factor Nrg4 preserves metabolic homeostasis through attenuation of hepatic lipogenesis. Nat Med. 2014; 20(12): 1436–1443.
  13. Zhang L, Fu Y, Zhou N, et al. Circulating neuregulin 4 concentrations in patients with newly diagnosed type 2 diabetes: a cross-sectional study. Endocrine. 2017 [Epub ahead of print]; 57(3): 535–538.
  14. Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome. Fertil Steril. 2004; 81: 19–25.
  15. FERRIMAN D, GALLWEY JD. Clinical assessment of body hair growth in women. J Clin Endocrinol Metab. 1961; 21: 1440–1447.
  16. Matthews DR, Hosker JP, Rudenski AS, et al. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985; 28(7): 412–419.
  17. Kang YE, Kim JiM, Choung S, et al. Comparison of serum Neuregulin 4 (Nrg4) levels in adults with newly diagnosed type 2 diabetes mellitus and controls without diabetes. Diabetes Res Clin Pract. 2016; 117: 1–3.
  18. Ojeda S, Urbanski H, Katz K, et al. Activation of Estradiol-Positive Feedback at Puberty: Estradiol Sensitizes the LHRH-Releasing System at Two Different Biochemical Steps. Neuroendocrinol. 1986; 43(2): 259–265.
  19. Ojeda SR, Urbanski HF, Costa ME, et al. Involvement of transforming growth factor alpha in the release of luteinizing hormone-releasing hormone from the developing female hypothalamus. Proc Natl Acad Sci U S A. 1990; 87(24): 9698–9702.
  20. Prevot V, Rio C, Cho GJ, et al. Normal female sexual development requires neuregulin-erbB receptor signaling in hypothalamic astrocytes. J Neurosci. 2003; 23(1): 230–239.
  21. Day FR, Hinds DA, Tung JY, et al. Causal mechanisms and balancing selection inferred from genetic associations with polycystic ovary syndrome. Nat Commun. 2015; 6: 8464.
  22. South JCM, Blackburn E, Brown IR, et al. The neuregulin system of ligands and their receptors in rat islets of langerhans. Endocrinology. 2013; 154(7): 2385–2392.
  23. Ma Y, Gao M, Liu D. Preventing High Fat Diet-induced Obesity and Improving Insulin Sensitivity through Neuregulin 4 Gene Transfer. Sci Rep. 2016; 6: 26242.
  24. Cai C, Lin M, Xu Y, et al. Association of circulating neuregulin 4 with metabolic syndrome in obese adults: a cross-sectional study. BMC Med. 2016; 14(1): 165.
  25. Jiang J, Lin M, Xu Y, et al. Circulating neuregulin 4 levels are inversely associated with subclinical cardiovascular disease in obese adults. Sci Rep. 2016; 6: 36710.
  26. Dehdashtihaghighat S, Mehdizadehkashi A, Arbabi A, et al. Assessment of C-reactive Protein and C3 as Inflammatory Markers of Insulin Resistance in Women with Polycystic Ovary Syndrome: A Case-Control Study. J Reprod Infertil. 2013; 14(4): 197–201.
  27. McElroy SJ, Castle SL, Bernard JK, et al. The ErbB4 ligand neuregulin-4 protects against experimental necrotizing enterocolitis. Am J Pathol. 2014; 184(10): 2768–2778.
  28. Bernard JK, McCann SP, Bhardwaj V, et al. Neuregulin-4 is a survival factor for colon epithelial cells both in culture and in vivo. J Biol Chem. 2012; 287(47): 39850–39858.

Regulations

Important: This website uses cookies. More >>

The cookies allow us to identify your computer and find out details about your last visit. They remembering whether you've visited the site before, so that you remain logged in - or to help us work out how many new website visitors we get each month. Most internet browsers accept cookies automatically, but you can change the settings of your browser to erase cookies or prevent automatic acceptance if you prefer.

By VM Media Group sp. z o.o., ul. Świętokrzyska 73, 80–180 Gdańsk
tel.:+48 58 320 94 94, faks:+48 58 320 94 60, e-mail:  viamedica@viamedica.pl