Growth hormone secretion and synthesis are depressed in obesity-susceptible compared with obesity-resistant rats

Human obesity is characterized by a low basal growth hormone (GH) concentration and a blunted response to GH secretagogues. The aim of this experiment was to determine whether a perturbation in GH synthesis or secretion occurs in rats that develop obesity only in response to a dietary fat challenge. Female Sprague-Dawley rats were fed a purified 32.5% fat diet ad libitum for 21 weeks. Approximately half of the rats fed this diet developed obesity (obesity-susceptible) while the others remained lean (obesity-resistant) compared with chow-fed (control) animals. Pituitary glands obtained from all three groups were enzymatically dissociated, and somatotrope response to GH secretagogues and inhibitors was determined in vitro. Plasma GH concentrations were decreased in obesity-susceptible rats compared with obesity-resistant rats, and in vitro GH secretory response was blunted in cells obtained from the pituitary glands of obese compared with lean rats. In addition, pituitary GH content was reduced in obese versus lean rats even though the proportion of somatotropes in the two groups did not differ. Since the changes in GH concentration in this dietary obese rat model parallel those found in human obesity, this model may be useful in determining the relationship between GH and obesity.