Elevated circulating levels of secreted frizzled-related protein 4 in relation to insulin resistance and androgens in women with polycystic ovary syndrome
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Secreted frizzled-related protein 4 (SFRP4) is an adipokine involving in apoptotic process during ovulation and energy metabolism. Polycystic ovary syndrome (PCOS) is a common reproductive and metabolic disorder associated with insulin resistance and impaired oocyte maturation as well as apoptotic dysfunctions through oocyte development. Our aim was to determine whether there was an alteration in levels of SFRP4 and if there was an association between metabolic or hormonal parameters and SFRP4 in women with PCOS.
We enrolled 80 subjects with PCOS and 80 age- and body mass index (BMI)-matched subjects with normal menstrual cycle into current case–control study. Metabolic and hormonal parameters of enrolled subjects were determined. Circulating SFRP4 levels were measured with ELISA method.
We found that circulating SFRP4 levels were elevated in women with PCOS with respect to controls (5.87 ± 1.91 vs. 3.72 ± 1.29 ng/ml, P < 0.001). We also found a positive association between SFRP4 and insulin resistance, androgens, ovarian follicular number or ovarian volume in women with PCOS. Binary logistic regression analysis revealed that subjects with the highest tertile of SFPR4 levels displayed increased possibility of having PCOS risk compared to those subjects with the lowest tertile of SFRP4 levels.
Increased SFRP4 levels were not only associated with higher possibility of having PCOS but also related to insulin resistance, hyperandrogenism, ovarian follicular number and ovarian volume, suggesting that SFPR4 could be a player in different pathophysiologic pathways of PCOS.
KeywordsPolycystic ovary syndrome Secreted frizzled-related protein 4 Insulin resistance Hyperandrogenism Ovarian follicular number
Body mass index
Coefficient of variability
Diastolic blood pressure
Free androgen index
Fasting blood glucose
High density lipoprotein cholesterol
Homeostasis model assessment of insulin resistance
High sensitivity C-reactive protein
Low density lipoprotein cholesterol
Polycystic ovary syndrome
Receiver Operator Characteristic
Secreted frizzled-related protein 4
Systolic blood pressure
Type 2 diabetes mellitus
Variance inflation factor
M.B., M.C., I.D., A.G, and P.A. participated in study design and B.A. and M.C. performed ELISA. M.B., M.C., I.D., A.G, P.A. and B.A. participated in study design, analyzed the data, wrote, reviewed and edited the manuscript. M.C., I.D., A.G. and P.A. provided serum samples and contributed to discussions of data interpretation. All authors reviewed and edited the manuscript. M.C. is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
This study has not been funded by any organizations.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
The study adhered strictly to the principles of the Declaration of Helsinki as revised in 2008.
The subjects gave their oral and written informed consent before their inclusion in the study.
- 1.Piltonen TT, Chen J, Erikson DW, Spitzer TLB, Barragan F, Rabban JT, Huddleston H, Irwin JC, Giudice LC (2013) Mesenchymal stem/progenitors and other endometrial cell types from women with polycystic ovary syndrome (PCOS) display ınflammatory and oncogenic potential. J Clin Endocrinol Metab 98:3765–3775CrossRefGoogle Scholar
- 2.Mahdi T, Hänzelmann S, Salehi A, Muhammed SJ, Reinbothe TM, Tang Y, Axelsson AS, Zhou Y, Jing X, Almgren P, Krus U, Taneera J, Blom AM, Lyssenko V, Esguerra JLS, Hansson O, Eliasson L, Derry J, Zhang E, Wollheim CB, Groop L, Renström E, Rosengren AH (2012) Secreted frizzled-related protein 4 reduces ınsulin secretion and ıs overexpressed in type 2 diabetes. Cell Metab 16:625–633CrossRefGoogle Scholar
- 8.Abu-Jawdeh G, Comella N, Tomita Y, Brown LF, Tognazzi K, Sokol SY, Kocher O (1999) Differential expression of frpHE: a novel human stromal protein of the secreted frizzled gene family, during the endometrial cycle and malignancy. Lab Invest 79:439–447Google Scholar
- 11.Anand K, Vidyasagar S, Lasrado I, Pandey GK, Amutha A, Ranjani H, Mohan Anjana R, Mohan V, Gokulakrishnan K (2016) Secreted frizzled-related protein 4 (SFRP4): a novel biomarker of β-cell dysfunction and ınsulin resistance in ındividuals with prediabetes and type 2 diabetes. Diabetes Care 39:e147–e148CrossRefGoogle Scholar
- 12.Baldane S, Ipekci SH, Ekin A, Abusoglu S, Unlu A, Kebapcilar L (2018) Evaluation of fractalkine (FKN) and secreted frizzled-related protein 4 (SFRP-4) serum levels in patients with prediabetes and type 2 diabetes. Bratisl Lek Listy 119:112–115Google Scholar
- 13.Baldane S, Ipekci SH, Kebapcilar AG, Abusoglu A, Beyhekim H, Ilhan TT, Unlu A, Kebapcilar A (2018) Prorenin and secreted frizzled-related protein 4 levels in women with gestational diabetes mellitus. Bratisl Lek Listy 119:450–453Google Scholar
- 19.Dunaif A (1997) Insulin resistance and the polycystic ovary syndrome: mechanism and implications for pathogenesis. Endocr Rev 18:774–800Google Scholar
- 27.Friedewald WT, Levy RI, Fredrickson DS (1972) Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 18:499–502Google Scholar