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

Temür, Muzaffer; Çalan, Mehmet; Akşit, Murat; Yılmaz, Özgür; Çift, Tayfur; Akselim, Burak; Çakmak, Burcu Dinçgez; Üstünyurt, Emin

doi:10.5603/gp.a2017.0095

Cited by 13 publications

(7 citation statements)

References 26 publications

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“…The ERBB4 receptor gene was associated with PCOS on the basis of a GWAS in Caucasian patients (15,31) and replicated by a case-control study in Chinese patients (32). ERBB4 encodes a receptor activated by neuregulin (NRG)4 (33), and serum levels of NRG4 were found to be elevated in patients with PCOS (34,35). In a well-powered GWAS with the application of a subphenotyping algorithm (phenome-wide association study) for PCOS using electronic records, ERBB4 was found to be associated with oligomenorrhea or infertility.…”

Section: Ligands and Receptorsmentioning

confidence: 90%

A kaleidoscopic view of ovarian genes associated with polycystic ovary syndrome

2021

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Polycystic ovary syndrome (PCOS) is the most common endocrine and metabolic disorder affecting 6%-10% of reproductive-age women, and it is associated with defects in follicle functions. On the basis of advances in the evaluation of gene variants, together with family-based and genome-wide association studies, we discussed genes associated with PCOS. We used a gene-centric approach to sort out literature deposited in the Ovarian Kaleidoscope database (http://okdb.appliedbioinfo.net) by subcategorizing candidate genes as ligand-receptor signaling, meiosis and deoxyribonucleic acid repair, transcriptional factors, ribonucleic acid metabolism, enzymes, and others. Although multiple individual candidate genes with single nucleotide polymorphisms have been identified in patients with PCOS, only a limited number of findings have been verified and deal with genes with known ovarian functions. On the basis of genome-wide association studies, a limited group of PCOS candidate genes, including FSHB, FSHR, LHR, YAP1, AOPEP/C9orf3, RAB5/SUOX, THADA, and DENND1A, yielded consistent association in good-quality studies in both Caucasian and Chinese populations. Although some of these genes have known ovarian functions, the ovarian expression and function of others remain to be elucidated. Overall, PCOS candidate genes are likely associated with abnormal gene expression because of their recent evolutionary origins. Studying rare variants in complex diseases such as PCOS presents unique challenges. The identification of rare variants and functional gene networks by next-generation sequencing along with epigenetic studies may increase our understanding of the genetic bases of PCOS. A better definition of unique diseases underlying PCOS on the basis of ovarian expression patterns could provide new diagnosis and treatments.

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Section: Ligands and Receptorsmentioning

confidence: 90%

A kaleidoscopic view of ovarian genes associated with polycystic ovary syndrome

2021

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“…A subsequent study also proposed that hepatic Nrg4 signaling could be an endocrine checkpoint for steatosis-to-steatohepatitis progression by countering stress-induced liver injury, fibrosis and cell death (21). In addition, several studies in human cohorts revealed that Nrg4 levels were increased in patients with prediabetes, newly diagnosed diabetes, gestational diabetes or polycystic ovary syndrome, suggesting Nrg4 concentrations were associated with the development and progression of insulin resistance (22, 23, 24, 25). However, other findings indicate that circulating Nrg4 concentrations may be a protective factor in the development of metabolic syndrome.…”

Section: Discussionmentioning

confidence: 99%

Elevated serum neuregulin 4 levels in patients with hyperthyroidism

Chen

Jiang

et al. 2019

Endocrine Connections

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Objective Recent studies have shown that neuregulin 4 (Nrg4), a member of the epidermal growth factor (EGF) family of extracellular ligands, plays an important role in the prevention of obesity, insulin resistance and nonalcoholic fatty liver disease (NAFLD). Considering that thyroid hormone (TH) has profound effects on whole-body energy metabolism, we speculate that circulating Nrg4 levels might be altered in patients with hyperthyroidism. Design and methods A total of 129 hyperthyroid patients and 100 healthy subjects were recruited. Of them, 39 hyperthyroid patients received thionamide treatment for 3 months until euthyroidism. Serum Nrg4 levels were determined using the ELISA method. To further confirm the relationship between TH and Nrg4, C57BL/6 mice were treated with T3 and quantitative real-time PCR was performed to detect Nrg4 gene expression. Results Serum Nrg4 levels were significantly elevated in hyperthyroid patients as compared with normal controls (3.84 ± 1.63 vs 2.21 ± 1.04 ng/mL, P < 0.001). After achieving euthyroidism by thionamide treatment, serum Nrg4 levels dropped markedly from 3.57 ± 1.26 to 1.94 ± 0.72 ng/ml (P < 0.001). After adjustment for potential confounders, serum Nrg4 levels were independently associated with hyperthyroidism. The upregulation of Nrg4 expression in the livers and white adipose tissues by T3 was further confirmed by animal and cell culture experiments. Conclusions Serum Nrg4 levels were increased in patients with hyperthyroidism. The liver and white adipose tissue might be primary sources contributing to elevated serum Nrg4 concentrations.

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“…In 2017, Temur et al reported considerably higher serum levels of NRG4 in PCOS patients than in healthy controls [ 137 ]. High sensitivity C-reactive protein (Hs-CRP), low-density lipoproteins (LDL-C), HDL-C and hormones profile (LH; insulin; total testosterone; sex hormone binding globulin, SHBG; dehydroepiandrosterone sulfate, DHEA-SO 4 ), as well as other metabolism-related factors such as fasting blood glucose (FBG), FAI, and HOMA-IR, were also elevated in comparison to healthy individuals.…”

Section: Neuregulin-4mentioning

confidence: 99%

“…Positive correlations between NGR4 level and FBG, insulin, HOMA-IR and hs-CRP were observed in the study group. HOMA-IR, and hs-CRP proved to be independent markers associated with NRG4 [ 137 ]. Hypothetically, the high neuregulin level in PCOS subjects could be interpreted as a result of problems with NRG4 binding to epidermal growth factor receptor (EGFR); however, more research needs to be conducted to confirm this hypothesis [ 137 ].…”

Section: Neuregulin-4mentioning

confidence: 99%

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Review of Novel Potential Insulin Resistance Biomarkers in PCOS Patients—The Debate Is Still Open

Kruszewska

Laudy-Wiaderny²,

Kunicki

2022

IJERPH

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Research on proteins and peptides that play roles in metabolic regulation, which may be considered potential insulin resistance markers in some medical conditions, such as diabetes mellitus, obesity and polycystic ovarian syndrome (PCOS), has recently gained in interest. PCOS is a common endocrine disorder associated with hyperandrogenemia and failure of ovulation, which is often accompanied by metabolic abnormalities, including obesity, dyslipidemia, hyperinsulinemia, and insulin resistance. In this review, we focus on less commonly known peptides/proteins and investigate their role as potential biomarkers for insulin resistance in females affected by PCOS. We summarize studies comparing the serum fasting concentration of particular agents in PCOS individuals and healthy controls. Based on our analysis, we propose that, in the majority of studies, the levels of nesfastin-1, myonectin, omentin, neudesin were decreased in PCOS patients, while the levels of the other considered agents (e.g., preptin, gremlin-1, neuregulin-4, xenopsin-related peptide, xenin-25, and galectin-3) were increased. However, there also exist studies presenting contrary results; in particular, most data existing for lipocalin-2 are inconsistent. Therefore, further research is required to confirm those hypotheses, as well as to elucidate the involvement of these factors in PCOS-related metabolic complications.

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

Cited by 13 publications

References 26 publications

A kaleidoscopic view of ovarian genes associated with polycystic ovary syndrome

A kaleidoscopic view of ovarian genes associated with polycystic ovary syndrome

Elevated serum neuregulin 4 levels in patients with hyperthyroidism

Review of Novel Potential Insulin Resistance Biomarkers in PCOS Patients—The Debate Is Still Open

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