Johannes D Veldhuis1, Rebecca J Yang, Jean R Wigham, Dana Erickson, John C Miles, Cyril Y Bowers. 1. Endocrine Research Unit (J.D.V., R.J.Y., J.R.W., D.E., J.C.M.), Mayo Clinic College of Medicine Center for Translational Science Activities, Mayo Clinic, Rochester, Minnesota 55905; and Tulane University Health Sciences Center (C.Y.B.), Endocrinology and Metabolism Section, Peptide Research Section, New Orleans, Louisiana 70112.
Abstract
CONTEXT: Hyposomatotropism in healthy aging women reflects in part physiological estrogen (estradiol [E2]) depletion associated with menopause. OBJECTIVE AND DESIGN: The purpose of this study was to test the hypothesis that low concentrations of endogenous E2 after menopause continue to drive GH secretion. SETTING: The study was performed at the Mayo Center for Clinical and Translational Science. PARTICIPANTS: The participants were 24 postmenopausal women (aged 50-77 years with body mass index of 19-32 kg/m(2)). INTERVENTIONS: This was a randomized, double-blind, placebo-controlled, parallel-cohort treatment study with placebo (PL) (n = 14) or the antiestrogen fulvestrant (FUL) (n = 10) for 3 weeks, followed by infusion of l-arginine with saline, GHRH, ghrelin, or both peptide secretagogues. OUTCOMES: GH concentrations were measured over 6 hours with 10-minute sampling and mass spectrometry measures of testosterone, E2, and estrone. RESULTS:Concentrations of testosterone, E2, estrone, SHBG, IGF-I, LH, and FSH were not influenced by antiestrogen treatment. In contrast, GH rose from 0.096 ± 0.018 (PL) to 0.23 ± 0.063 μg/L (FUL, P = .033), and IGF-I binding protein type 3 (IGFBP-3) from 3.6 ± 0.18 to 4.0 ± 2.0 mg/L (P = .041). Conversely, prolactin fell from 7.1 ± 0.69 (PL) to 5.5 ± 0.57 μg/L (FUL) (P = .05), and IGF-I binding protein type 1 (IGFBP-1) fell from 44 ± 9.4 to 27 ± 4.3 μg/L (P = .048). Moreover, FUL vs PL potentiated mean GH responses to l-arginine/saline (P = .007), l-arginine/ghrelin (P = .008), and l-arginine/GHRH + ghrelin (P = .031), but not l-arginine/GHRH. CONCLUSION: The potent antiestrogen, FUL, amplifies fasting and secretagogue-driven GH secretion and IGFBP-3 concentrations in postmenopausal women without altering SHBG or sex steroid levels. FUL also suppresses prolactin and IGFBP-1, without altering IGF-I. Thus, a major antiestrogen mediates 3 actions of estrogen: agonism (GH), neutral effects (sex steroids), and estrogen antagonism (prolactin and IGFBP-1).
RCT Entities:
CONTEXT: Hyposomatotropism in healthy aging women reflects in part physiological estrogen (estradiol [E2]) depletion associated with menopause. OBJECTIVE AND DESIGN: The purpose of this study was to test the hypothesis that low concentrations of endogenous E2 after menopause continue to drive GH secretion. SETTING: The study was performed at the Mayo Center for Clinical and Translational Science. PARTICIPANTS: The participants were 24 postmenopausal women (aged 50-77 years with body mass index of 19-32 kg/m(2)). INTERVENTIONS: This was a randomized, double-blind, placebo-controlled, parallel-cohort treatment study with placebo (PL) (n = 14) or the antiestrogen fulvestrant (FUL) (n = 10) for 3 weeks, followed by infusion of l-arginine with saline, GHRH, ghrelin, or both peptide secretagogues. OUTCOMES: GH concentrations were measured over 6 hours with 10-minute sampling and mass spectrometry measures of testosterone, E2, and estrone. RESULTS: Concentrations of testosterone, E2, estrone, SHBG, IGF-I, LH, and FSH were not influenced by antiestrogen treatment. In contrast, GH rose from 0.096 ± 0.018 (PL) to 0.23 ± 0.063 μg/L (FUL, P = .033), and IGF-I binding protein type 3 (IGFBP-3) from 3.6 ± 0.18 to 4.0 ± 2.0 mg/L (P = .041). Conversely, prolactin fell from 7.1 ± 0.69 (PL) to 5.5 ± 0.57 μg/L (FUL) (P = .05), and IGF-I binding protein type 1 (IGFBP-1) fell from 44 ± 9.4 to 27 ± 4.3 μg/L (P = .048). Moreover, FUL vs PL potentiated mean GH responses to l-arginine/saline (P = .007), l-arginine/ghrelin (P = .008), and l-arginine/GHRH + ghrelin (P = .031), but not l-arginine/GHRH. CONCLUSION: The potent antiestrogen, FUL, amplifies fasting and secretagogue-driven GH secretion and IGFBP-3 concentrations in postmenopausal women without altering SHBG or sex steroid levels. FUL also suppresses prolactin and IGFBP-1, without altering IGF-I. Thus, a major antiestrogen mediates 3 actions of estrogen: agonism (GH), neutral effects (sex steroids), and estrogen antagonism (prolactin and IGFBP-1).
Authors: M J Bray; T M Vick; N Shah; S M Anderson; L W Rice; A Iranmanesh; W S Evans; J D Veldhuis Journal: J Clin Endocrinol Metab Date: 2001-07 Impact factor: 5.958
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