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.


METHODS
Pilot prospective study.


METHODS
Seven obese PCOS women and seven age-weight matched controls.


METHODS
Hormonal measurements, oral glucose tolerance test (OGTT) and a ghrelin test (1 microg/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.


CONCLUSIONS
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.
Romualdi
Daniela
D
Department of Obstetrics and Gynaecology, Università Cattolica del Sacro Cuore, L go Agostino Gemelli, Rome, Italy.
De Marinis
Laura
L
Campagna
Giuseppe
G
Proto
Caterina
C
Lanzone
Antonio
A
Guido
Maurizio
M
D000328:Adult; D005260:Female; D054439:Ghrelin / Q000097:blood* / Q000378:metabolism / Q000494:pharmacology; D005951:Glucose Tolerance Test; D006801:Humans; D006946:Hyperinsulinism / Q000097:blood / Q000150:complications* / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007328:Insulin / Q000097:blood / Q000378:metabolism; D020738:Leptin / Q000097:blood / Q000378:metabolism; D008687:Metformin / Q000627:therapeutic use; D009478:Neuropeptide Y / Q000097:blood* / Q000378:metabolism; D009765:Obesity / Q000097:blood* / Q000150:complications / Q000188:drug therapy / Q000378:metabolism; D010865:Pilot Projects; D011085:Polycystic Ovary Syndrome / Q000097:blood* / Q000150:complications / Q000188:drug therapy / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D055815:Young Adult
D054439:Ghrelin; D007004:Hypoglycemic Agents; D007328:Insulin; D020738:Leptin; D009478:Neuropeptide Y; D008687:Metformin