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OBJECTIVE: Ghrelin, a gastric-derived natural ligand of the GH secretagogue (GHS)-receptor (GHS-R), strongly stimulates GH secretion but also possesses other neuroendocrine actions, stimulates food intake and modulates the endocrine pancreas and energy homeostasis. Ghrelin secretion is negatively modulated by food intake. Similarly, glucose and also insulin probably exert an inhibitory effect on ghrelin secretion. Fasting ghrelin levels are reduced in obesity, elevated in anorexia nervosa and restored by weight recovery. The chronic elevation of circulating ghrelin levels in anorexia suggested the hypothesis of an alteration of the sensitivity to the orexigenic action of ghrelin in this condition. The aim of this study was to define the endocrine actions of ghrelin in patients with anorexia nervosa. DESIGN: We enrolled nine women with anorexia nervosa of restricter type [AN; age (mean ± SEM) 24.2 ± 1.8 years; body mass index (BMI) 14.7 ± 0.4 kg/m²] and seven normal young women in their early follicular phase as control group (NW; age 30.6 ± 3.1 years; BMI 20.3 ± 0.5 kg/m²). MEASUREMENTS: In all the subjects we studied the GH, PRL, ACTH, cortisol, insulin and glucose responses to acute ghrelin administration (1.0 μg/kg as i.v. bolus). The GH response to GHRH (1.0 μg/kg as i.v. bolus) and basal ghrelin and IGF-I levels were also evaluated in all the subjects. RESULTS Basal morning ghrelin and GH levels in AN (643.6 ± 21.3 ng/l and 10.4 ± 0.5 μg/l, respectively) were higher ( P < 0.05) than in NW (233.5 ± 14.2 ng/ l and 0.7 ± 0.7 μg/l, respectively). However, IGF-I levels in AN (145.3 ± 10.9 μg/l) were lower ( P < 0.05) than in NW (325.4 ± 12.6 μg/l). The GH response to GHRH in AN was higher ( P < 0.05) than that in NW, but in AN the GH response to ghrelin was lower ( P < 0.05) than that in NW. In AN and NW ghrelin also induced similar increases ( P < 0.05) in PRL, ACTH and cortisol levels. Ghrelin administration was followed by significant increase in glucose levels in NW ( P < 0.05) but not in AN. CONCLUSIONS: This study demonstrates that anorexia nervosa, a clinical condition of ghrelin hypersecretion, shows a specific reduction in the GH response to ghrelin, despite the hyper-responsiveness to GHRH administration. The impaired GH response to ghrelin in anorexia nervosa agrees with previous evidence of blunted GH response to synthetic GH secretagogues and could reflect desensitization of the GHS receptor induced by the chronic elevation of ghrelin levels in this pathological state. [ABSTRACT FROM AUTHOR]

Summary aim GnRH antagonists are competitive inhibitors of GnRH receptors. Their administration induces prompt suppression of the gonadal axis. In animals, GnRH antagonists upregulate the activity of GnRH-secreting neurones, which could cause gonadotrophin rebound following inhibition. The aim of this study was to evaluate the effects of a potent GnRH antagonist, Teverelix (TEV), on the gonadal axis in healthy young women. subjects and measurements In nine women [20–35 years old, body mass index (BMI) 19–25 kg/m[sup 2] ] in the early follicular phase, serum LH and FSH levels were evaluated every 10 min from 08·00 to 12·00 h before, and 24 h and 96 h after TEV injection (2·5 mg in 1 ml subcutaneusly on day 0). Serum gonadotrophin and oestradiol levels were also evaluated at baseline and at 6, 8, 12, 48, 72 h after TEV. results The antagonist reduced both serum LH and FSH concentrations; LH levels were significantly and promptly reduced at +6 h (nadir at +8 h) until +48 h and recovered at +72 h, while FSH levels were reduced (P < 0·05) 24 h after the antagonist and normalized at +48 h. LH (but not FSH) concentrations at +96 h exceeded baseline (P < 0·05). TEV suppressed oestradiol concentrations (P < 0·05) with a nadir at +24 h, comparable reduction at +48 h and recovery to baseline at +72 h. Deconvolution analysis showed that the antagonist peptide suppressed (P < 0·02) the pulsatile production rate, burst mass and amplitude of LH on day 1. Pulsatile FSH secretion also fell at this time (P < 0·05). LH and FSH pulse frequency were not modified by TEV. At +96 h, LH pulsatility did not significantly differ from that at baseline. Suppression of mean LH or FSH concentrations did not affect the relative pattern regularity (approximate entropy) of LH and FSH secretion. conclusions This study demonstrates that the acute administration of a potent GnRH antagonist induces prompt inhibition of the gonadal axis lasting for 2 days in women due to mechanistically specific suppression of LH secretory burst mass and the mean FSH secretion rate. The trend toward rebound release of LH following the end of the pharmacological effect of the antagonist could reflect a rise in endogenous GnRH activity. [ABSTRACT FROM AUTHOR]