Alteration of ghrelin-neuropeptide Y network in obese patients with polycystic ovary syndrome: Role of hyperinsulinism

Objective: Insulin, ghrelin, neuropeptide Y (NPY) and leptin interact in the regulation of energy homeostasis. Most of these signals are altered in polycystic ovary syndrome (PCOS), which is characterized by a high prevalence of obesity. The present study was conducted to evaluate ghrelin-NPY and ghrelin-leptin interplays in relation to insulin secretion in obese PCOS subjects. Design: Pilot prospective study. Patients: Seven obese PCOS women and seven age-weight matched controls. Measurements: Hormonal measurements, oral glucose tolerance test (OGTT) and a ghrelin test (1 μg/kg i.v. bolus). PCOS patients repeated the clinical work-up after 4 months of metformin treatment (1500 mg/day orally). Results: At baseline, PCOS women showed a significantly higher insulinaemic response to the OGTT compared to controls (P <0.05). In basal conditions, PCOS women exhibited lower NPY levels than controls (P <0.01). Ghrelin injection markedly increased NPY in controls (P <0.01), whereas PCOS women showed a deeply blunted NPY response to the stimulus (area under the curve - AUC-NPY: P <0.01 vs. controls.). Metformin treatment induced a significant decrease in insulin levels (P <0.01) and the concomitant recovery of NPY secretory capacity in response to ghrelin (AUC-NPY: P <0.05 vs. baseline) in PCOS women. Leptin levels, which were similar in the two groups, were not modified by ghrelin injection; metformin did not affect this pattern. Conclusion: Hyperinsulinaemia seems to play a pivotal role in the alteration of NPY response to ghrelin in obese PCOS women. This derangement could be implicated in the physiopatology of obesity in these patients.