Growth hormone (GH) secretion is markedly blunted in obesity. Reportedly, genetically obese Zucker rats show a reduced GH secretion due to an impaired function of hypothalamic neurons producing the GH-releasing hormone (GHRH). The aim of this work was: (1) to compare the in vitro GH responsiveness to GHRH in genetically obese female versus male Zucker rats and, (2) to evaluate the function of hypothalamic GHRH and somatostatin and of pituitary receptors for these neurohormones as assessed by the effectiveness of GHRH and somatostatin on adenylate cyclase (AC) activity. Baseline GH secretion of pituitaries obtained from male and female obese rats was not different and similar to that present in lean counterparts. Stimulation with 10–7M GHRH elicited a significantly lower GH secretion from the pituitaries of lean and obese female rats. In these pituitaries of obese male rats, but induced a similar GH secretion from the pituitaries, GH concentration was similar in obese versus lean male and female rats. A sex-related difference was also evidenced when plasma concentrations of somatomedin C (IGF-1) were evaluated. Obese male rats had lower IGF-1 concentrations than lean counterparts, while this was not the case for obese versus lean female rats. Evaluation of AC activity following GHRH disclosed a lower activation in obese than in lean male rats, whereas in the females the enzyme activation was higher in obese than in lean animals. Conversely, the inhibitory effect of somatostatin on forskolin-stimulated AC was similar in pituitary membranes of obese and lean rats of both sexes. Determination of GHRH mRNA in the hypothalamus of obese rats showed that it was significantly reduced in male but not in female obese rats versus lean counterparts. In contrast, somatostatin mRNA concentrations were unchanged in the hypothalamus of obese rats of both sexes. Overall these data suggest that despite an in vivo reduced GH secretion, the hypothalamo-pituitary GH regulatory system is more preserved in female than in male obese rat