Study of circulating hepcidin in association with iron excess, metabolic syndrome, and BMP-6 expression in granulosa cells in women with polycystic ovary syndrome

Fertil Steril. 2014 Aug;102(2):548-554.e2. doi: 10.1016/j.fertnstert.2014.04.031. Epub 2014 May 27.

Abstract

Objective: To identify the role of hepcidin in polycystic ovary syndrome (PCOS) patients.

Design: Cross-sectional case-control study.

Setting: Academic medical center.

Patient(s): Sixty-seven PCOS patients and 94 healthy parous women volunteered for the study.

Intervention(s): None.

Main outcome measure(s): Serum levels of hepcidin, hormone and lipid profiles, parameters of iron and glucose metabolism, high-sensitivity C-reactive protein (hs-CRP), and bone morphogenetic protein 6 (BMP-6) mRNA expressions in the granulosa cells (GCs).

Result(s): PCOS patients showed increased serum iron concentration and higher circulating hepcidin levels compared with control subjects, even with only lean subjects. Circulating hepcidin correlated with iron parameters, androgen index, hs-CRP, and fasting glucose and insulin levels, and with iron and ferritin levels after multiple regression analysis. We analyzed BMP-6 mRNA expression in the 89 GCs from nine PCOS patients and five non-PCOS women with the use of quantitative real-time polymerase chain reaction, and no correlations existed between iron parameters, including circulating hepcidin, and BMP-6 expression in the GCs from PCOS women.

Conclusion(s): PCOS patients had iron excess and higher hepcidin levels, which are associated with metabolic derangements. Circulating hepcidin is appropriately increased relative to the iron burden even in PCOS women, suggesting that iron excess in PCOS women does not result from a defect in the production of hepcidin. But there were no correlations between iron parameters and the expression of the BMP-6 in GCs from PCOS patients.

Keywords: BMP-6; Polycystic ovary syndrome; hepcidin; iron excess; metabolic syndrome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biomarkers / blood
  • Bone Morphogenetic Protein 6 / genetics
  • Bone Morphogenetic Protein 6 / metabolism*
  • Case-Control Studies
  • Cross-Sectional Studies
  • Female
  • Granulosa Cells / metabolism*
  • Hepcidins / blood*
  • Humans
  • Iron / blood*
  • Metabolic Syndrome / blood*
  • Metabolic Syndrome / diagnosis
  • Polycystic Ovary Syndrome / blood*
  • Polycystic Ovary Syndrome / diagnosis
  • Polycystic Ovary Syndrome / genetics
  • RNA, Messenger / analysis
  • Real-Time Polymerase Chain Reaction
  • Up-Regulation

Substances

  • BMP6 protein, human
  • Biomarkers
  • Bone Morphogenetic Protein 6
  • Hepcidins
  • RNA, Messenger
  • Iron