Decreased soluble leptin receptor levels in women with polycystic ovary syndrome

Abstract

Objective: Polycystic ovary syndrome (PCOS) is associated with insulin resistance and a high incidence of obesity. Leptin, the product of the ob gene, is involved in the regulation of energy balance and obesity and circulates in both free and bound forms. The soluble leptin receptor (sOB-R) is the most important leptin-binding protein, thus influencing the biologically active free leptin level. Design: We assessed the correlation of metabolic and endocrine parameters with leptin and sOB-R levels in 122 PCOS women (aged 27^5.7 years) and 81 healthy controls (aged 25^4.0 years). Methods: Leptin and sOB-R levels were measured using ELISA kits. In addition, anthropometric variables, body fat and endocrine parameters were evaluated and a glucose tolerance test performed to assess indices of insulin resistance and glucose metabolism. Results: In PCOS patients, no correlation was found between leptin or sOB-R and parameters of hyperandrogenism. However, as expected, body mass index (BMI), body fat, waist circumference and indices of insulin resistance were significantly correlated with leptin in PCOS subjects and controls. In a subgroup analysis of lean, overweight and obese PCOS patients, significant differences were found in leptin (29.7^20.7 vs 45.4^25.0 vs 67.7^28.8 ng/ml, P , 0.0001) and sOB-R (8.0^3.4 vs 6.4^2.5 vs 5.7^2.3 ng/ml, P , 0.05). Compared with BMI-matched controls, lean PCOS patients had lower sOB-R levels (8.0^3.4 vs 12.7^4.7 ng/ml, P , 0.0001) and higher free leptin indices (4.5^3.9 vs 2.8^2.2, P ¼ 0.0285). Conclusion: Taking into account that low sOB-R levels supposedly compensate diminished leptin action, PCOS per se might cause leptin resistance.European Journal of Endocrinology 154 287-294

Does an altered leptin axis play a role in obesity among children and adolescents with classical congenital adrenal hyperplasia due to 21-hydroxylase deficiency?

“…Moreover, the levels of sOB-R are also correlated negatively with TS in both girls and boys (26). Recently, in women with PCOS, which show similarity to patients with CAH elevated androgen levels, there is evidence for decreased serum levels of sOB-R, even though there was no significant correlation with androgen levels themselves (14). By contrast, a second study on the leptin axis in PCOS showed a negative correlation of sOB-R with DHEAS concentration (rZ0.35) (35).…”

20 YEARS OF LEPTIN: Role of leptin in human reproductive disorders

“…Women with PCOS may actually have higher free concentrations of leptin. Hahn et al (2006) have found lower concentrations of soluble leptin receptors and have proposed this to be a mechanism to compensate for leptin resistance.…”

“…However, the significance of this is unclear (Sir-Petermann et al 1999). Leptin concentrations are negatively associated with SHBG and free concentrations of sex steroids , Hahn et al 2006, although this may be related to the negative effect of insulin resistance on SHBG concentrations.…”

“…Studies show that leptin concentrations do correlate with homeostasis model assessment insulin resistance index as well as triglyceride concentrations (Hahn et al 2006, Pehlivanov & Mitkov 2009, Yildizhan et al 2011. The interactions between leptin and insulin signaling pathways prove to be complex, with leptin differentially modifying the metabolic effects of leptin.…”

Leptin concentrations in patients with polycystic ovary syndrome before and after met-formin treatment depending on insulin resistance, body mass index and androgen con-centrations--introductory report.

“…According to different sources it can be observed in 5-8 % of women of reproductive age [1,2]. At present, PCOS is diagnosed on the basis of Rotterdam Sponsored Consensus Workshop Group criteria established at the conference of European Society for Human Reproduction and Embryology and American Society for Reproductive Medicine (ESHRE/ASRM) in 2003 [3].…”