title: Impact of long-term naltrexone treatment on growth hormone and insulin secretion in hyperandrogenic and normal obese patients.
abstract: The growth hormone (GH) response to stimulation tests is impaired in obesity. Moreover, obese patients exhibit a "paradoxical" increase of GH to GH-releasing hormone (GHRH) stimulation after food ingestion; this paradoxical response is reversed by naloxone infusion. On the other hand, beta-endorphin seems to exert profound effects on insulin release. Recent studies also demonstrated an impairment of GH response to several stimuli in polycystic ovary syndrome (PCOS), a condition associated with obesity, hyperinsulinism, and insulin resistance. Chronic inhibition of opioid tone by the opioid antagonist naltrexone (NTX) is able to reduce the insulin response to an oral glucose tolerance test (OGTT) in hyperinsulinemic PCOS patients. Since insulin and GH may reciprocally influence their secretion and the opioid system may have a role in the pathogenesis of hyperinsulinemia and reduced GH secretion, we have explored the involvement of these neuroendocrine mechanisms in essential obesity and in obesity associated with hyperandrogenism by a long-term treatment with an opiate antagonist. We tested seven obese patients affected by PCOS, seven matched women with essential obesity (EO), and five non-obese control subjects. All patients, in the follicular phase, underwent an OGTT (75 g) and basal hormone assay. Two days later, patients were subjected to a GHRH test. The patients then had 4 weeks of treatment with NTX 50 mg/d. Following continuation of the treatment, OGTT and GHRH tests were repeated. Insulin-like growth factor-I (IGF-I) and IGF-binding protein-3 (IGFBP-3) plasma concentrations were also determined in the basal condition before and after NTX treatment. NTX treatment reduced fasting insulin levels in patients with EO (P < .05) and restored a normal GH response to GHRH without affecting IGF-1 and IGFBP-3 levels. In PCOS subjects, NTX reduced the insulin response to a glucose load and failed to modify the blunted GH response to GHRH. Our data suggest a significant difference in opioid system function in PCOS and EO subjects, indicating a particular form of obesity in PCOS. The opiate antagonist treatment in EO may act through the reduction of negative insulin feedback on GH secretion. In PCOS patients, the failure to improve GH secretion in obese hyperandrogenized patients may be related to a high opioidergic tone or to the inhibitory predominance of other neurotransmitters.
authors.affiliation: Institute of Gynecology and Obstetrics, Department of Internal Medicine II, Catholic University School of Medicine, Rome, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Villa
authors.forename: A M
authors.initials: AM
authors.lastname: Fulghesu
authors.forename: L
authors.initials: L
authors.lastname: De Marinis
authors.forename: D
authors.initials: D
authors.lastname: Valle
authors.forename: A
authors.initials: A
authors.lastname: Mancini
authors.forename: V
authors.initials: V
authors.lastname: Pavone
authors.forename: A
authors.initials: A
authors.lastname: Caruso
authors.forename: A
authors.initials: A
authors.lastname: Lanzone
mesh_terms: D000328:Adult; D005260:Female; D005951:Glucose Tolerance Test; D013007:Growth Hormone-Releasing Hormone; D006728:Hormones / Q000097:blood; D019382:Human Growth Hormone / Q000378:metabolism*; D006801:Humans; D017588:Hyperandrogenism / Q000188:drug therapy* / Q000378:metabolism*; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D000078790:Insulin Secretion; D009271:Naltrexone / Q000008:administration & dosage* / Q000627:therapeutic use; D009292:Narcotic Antagonists / Q000008:administration & dosage* / Q000627:therapeutic use; D009765:Obesity / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism*; D011085:Polycystic Ovary Syndrome / Q000150:complications; D012016:Reference Values; D013997:Time Factors
chemical_list: D006728:Hormones; D007328:Insulin; D009292:Narcotic Antagonists; D019382:Human Growth Hormone; D009271:Naltrexone; D013007:Growth Hormone-Releasing Hormone