TY - JOUR
T1 - Estradiol potentiates ghrelin-stimulated pulsatile growth hormone secretion in postmenopausal women
AU - Veldhuis, Johannes D.
AU - Keenan, Daniel M.
AU - Iranmanesh, Ali
AU - Mielke, Kristi
AU - Miles, John M.
AU - Bowers, Cyril Y.
N1 - Funding Information:
This work was supported in part by General Clinical Research Center Grant MO1 RR00585 to the Mayo Clinic and Foundation from the National Center for Research Resources (Rockville, MD) and Grant R01 NIA AG014799 from the National Institutes of Health (Bethesda, MD).
PY - 2006
Y1 - 2006
N2 - Context: Ghrelin and an estrogen-rich milieu individually amplify pulsatile GH secretion by increasing the amount of hormone released per burst. However, how these distinct agonists interact in controlling pulsatile GH output is not known. Objective: The objective of the study was to test the hypothesis that elevated estradiol (E2) concentrations potentiate hypothalamo-pituitary responses to a near-physiological ghrelin stimulus. Design: This was a double-blind, placebo-controlled, prospectively randomized, parallel-cohort study. Setting: The study was conducted at an academic medical center. Subjects: Twenty-one postmenopausal women participated in the study. Interventions: Eleven subjects received placebo (Pl) and 10 others E2 transdermally in escalating doses over 3 wk to mimic late follicular-phase E2 concentrations. Saline or a submaximally stimulatory amount of ghrelin (0.3 μg/kg) was infused iv on separate randomly ordered mornings fasting after 17-21 d of Pl or E2 administration. Outcomes: Outcomes included serum concentrations of E2, ghrelin, GH, IGF-I, IGF binding protein (IGFBP)-1 and IGFBP-3, and the estimated mass and waveform of stimulated GH secretory bursts. Results: Administration of E2 yielded late follicular-phase E2 concentrations. Compared with Pl, E2 did not alter ghrelin concentrations but reduced IGF-I and IGFBP-3 and elevated IGFBP-1 concentrations. Compared with saline, ghrelin infusion amplified pulsatile GH secretion by 7.1-fold (P < 0.01). The effect of E2 alone was 2.0-fold placebo and that of combined ghrelin/E2 10.4-fold (P < 0.01). Ghrelin and E2 accelerated initial GH release individually but nonadditively by more than 2-fold (P < 0.01). Conclusions: Estrogen augments ghrelin's near-physiological stimulation of pulsatile GH secretion and mimics ghrelin's acceleration of initial GH release. Thus, we hypothesize that estrogen and a GH secretagogue act via independent as well as convergent mechanisms.
AB - Context: Ghrelin and an estrogen-rich milieu individually amplify pulsatile GH secretion by increasing the amount of hormone released per burst. However, how these distinct agonists interact in controlling pulsatile GH output is not known. Objective: The objective of the study was to test the hypothesis that elevated estradiol (E2) concentrations potentiate hypothalamo-pituitary responses to a near-physiological ghrelin stimulus. Design: This was a double-blind, placebo-controlled, prospectively randomized, parallel-cohort study. Setting: The study was conducted at an academic medical center. Subjects: Twenty-one postmenopausal women participated in the study. Interventions: Eleven subjects received placebo (Pl) and 10 others E2 transdermally in escalating doses over 3 wk to mimic late follicular-phase E2 concentrations. Saline or a submaximally stimulatory amount of ghrelin (0.3 μg/kg) was infused iv on separate randomly ordered mornings fasting after 17-21 d of Pl or E2 administration. Outcomes: Outcomes included serum concentrations of E2, ghrelin, GH, IGF-I, IGF binding protein (IGFBP)-1 and IGFBP-3, and the estimated mass and waveform of stimulated GH secretory bursts. Results: Administration of E2 yielded late follicular-phase E2 concentrations. Compared with Pl, E2 did not alter ghrelin concentrations but reduced IGF-I and IGFBP-3 and elevated IGFBP-1 concentrations. Compared with saline, ghrelin infusion amplified pulsatile GH secretion by 7.1-fold (P < 0.01). The effect of E2 alone was 2.0-fold placebo and that of combined ghrelin/E2 10.4-fold (P < 0.01). Ghrelin and E2 accelerated initial GH release individually but nonadditively by more than 2-fold (P < 0.01). Conclusions: Estrogen augments ghrelin's near-physiological stimulation of pulsatile GH secretion and mimics ghrelin's acceleration of initial GH release. Thus, we hypothesize that estrogen and a GH secretagogue act via independent as well as convergent mechanisms.
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U2 - 10.1210/jc.2006-0948
DO - 10.1210/jc.2006-0948
M3 - Article
C2 - 16804038
AN - SCOPUS:33748751587
SN - 0021-972X
VL - 91
SP - 3559
EP - 3565
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
IS - 9
ER -