Catalina Norman1, Nanette Rollene, Suanne M Weist, Jean R Wigham, Dana Erickson, John M Miles, Cyril Y Bowers, Johannes D Veldhuis. 1. Endocrine Research Unit (C.N., S.M.W., J.R.W., D.E., J.M.M., J.D.V.), Mayo School of Graduate Medical Education, Center for Translational Science Activities, Mayo Clinic, Rochester, Minnesota 55905; Naval Medical Center Portsmouth (N.R.), Division of Reproductive Endocrinology, Portsmouth, Virginia 23708; and Tulane University Health Sciences Center (C.Y.B.), Endocrinology and Metabolism Section, Peptide Research Section, New Orleans, Louisiana 70112.
Abstract
CONTEXT: Ghrelin is a potent gastric-derived GH-releasing peptide. How ghrelin interacts with sex steroids, GHRH, and somatostatin (SS) is not known. OBJECTIVE: Our objective was to test the hypotheses that ghrelin's interactions with GHRH (synergistic) and SS (disinhibitory) are ghrelin dose-dependent and amplified by estrogen. SUBJECTS, SETTING, AND DESIGN:Healthy postmenopausal women were treated with placebo (n=12) or 17β-estradiol (E2) (n=12) at the Center for Translational Science Activities in a randomized double-blind prospective study. METHODS: Ghrelin dose-dependence was assessed by nonlinear curve fitting of the relationship between deconvolved GH secretory-burst mass and 5 randomly ordered ghrelin doses (0, 0.03, 0.135, 0.6, and 2.7 μg/kg bolus iv) during saline, GHRH, and SS infusion. RESULTS: Under placebo, neither GHRH nor SS altered the ED50 of ghrelin (range 0.64-0.67 μg/kg). Under E2 (median E2 88 pg/mL), the ED50 of ghrelin declined in the presence of GHRH to 0.52 μg/kg. In contrast, the efficacy of ghrelin rose markedly during GHRH vs saline exposure with and without E2: placebo and saline 52±1.0 vs GHRH 173±3.8 μg/L; and E2 and saline 56±0.90 vs GHRH 174±3.7 μg/L. Sensitivity to ghrelin was similar under all conditions. SUMMARY: Short-term E2 supplementation in postmenopausal women reduces the ED50 (increases the potency) of ghrelin when GHRH is present, without altering ghrelin efficacy (maximal effect) or hypothalamo-pituitary sensitivity (slope of dose response) to ghrelin. The data suggest possible physiological interactions among sex steroids (endogenous), ghrelin, and GHRH during E2 replacement in postmenopausal women.
RCT Entities:
CONTEXT: Ghrelin is a potent gastric-derived GH-releasing peptide. How ghrelin interacts with sex steroids, GHRH, and somatostatin (SS) is not known. OBJECTIVE: Our objective was to test the hypotheses that ghrelin's interactions with GHRH (synergistic) and SS (disinhibitory) are ghrelin dose-dependent and amplified by estrogen. SUBJECTS, SETTING, AND DESIGN: Healthy postmenopausal women were treated with placebo (n=12) or 17β-estradiol (E2) (n=12) at the Center for Translational Science Activities in a randomized double-blind prospective study. METHODS:Ghrelin dose-dependence was assessed by nonlinear curve fitting of the relationship between deconvolved GH secretory-burst mass and 5 randomly ordered ghrelin doses (0, 0.03, 0.135, 0.6, and 2.7 μg/kg bolus iv) during saline, GHRH, and SS infusion. RESULTS: Under placebo, neither GHRH nor SS altered the ED50 of ghrelin (range 0.64-0.67 μg/kg). Under E2 (median E2 88 pg/mL), the ED50 of ghrelin declined in the presence of GHRH to 0.52 μg/kg. In contrast, the efficacy of ghrelin rose markedly during GHRH vs saline exposure with and without E2: placebo and saline 52±1.0 vs GHRH 173±3.8 μg/L; and E2 and saline 56±0.90 vs GHRH 174±3.7 μg/L. Sensitivity to ghrelin was similar under all conditions. SUMMARY: Short-term E2 supplementation in postmenopausal women reduces the ED50 (increases the potency) of ghrelin when GHRH is present, without altering ghrelin efficacy (maximal effect) or hypothalamo-pituitary sensitivity (slope of dose response) to ghrelin. The data suggest possible physiological interactions among sex steroids (endogenous), ghrelin, and GHRH during E2 replacement in postmenopausal women.
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