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Raised Serum, Adipocyte, and Adipose Tissue Retinol-Binding Protein 4 in Overweight Women with Polycystic Ovary Syndrome: Effects of Gonadal and Adrenal Steroids

Endocrinology and Metabolism Group, Clinical Sciences Research Institute, Warwick Medical School, University of Warwick, Coventry CV4 7AL, United Kingdom

Address all correspondence and requests for reprints to: Dr. Harpal S. Randeva, Endocrinology and Metabolism Group, Clinical Sciences Research Institute, Warwick Medical School, University of Warwick, Coventry CV4 7AL, United Kingdom. E-mail: harpal.randeva{at}warwick.ac.uk.

Context: Polycystic ovary syndrome (PCOS) is associated with insulin resistance and obesity. Recent studies have shown that serum retinol-binding protein 4 (RBP4) levels increase with obesity. Currently, no data exist on the relative expression of RBP4 in either serum or adipose tissue of PCOS women.

Objectives: mRNA expression of RBP4 from sc and omental (om) adipose tissue and sc adipocytes in overweight PCOS women were compared with matched controls; RBP4 protein in adipose tissue and serum RBP4 levels were also assessed. Additionally, we studied the effects of testosterone, 17ß-estradiol, androstenedione, and dehydroepiandrosterone sulfate on RBP4 expression in adipose tissue explants.

Design: Real-time RT-PCR and Western blotting were used to assess the relative mRNA and protein expression of RBP4. Biochemical measurements were also performed.

Results: Compared with controls, there was significant up-regulation of RBP4 mRNA in sc (P < 0.05) and om (P < 0.01) adipose tissue as well as isolated sc adipocytes (P < 0.01) of PCOS women. In addition to elevated serum RBP4 levels in PCOS women (P < 0.05), RBP4 protein levels were significantly greater in sc and om adipose tissue of PCOS women (P < 0.05 and P < 0.05, respectively). Furthermore, in human sc and om adipose tissue explants, 17ß-estradiol significantly increased RBP4 mRNA expression, protein levels, and secretion into the culture media (P < 0.05).

Conclusions: The precise reason for elevated levels of RBP4 in overweight PCOS women is unknown, but it appears that 17ß-estradiol may play a role in their regulation in adipose tissue.

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