Estrogen supplementation selectively enhances hypothalamo-pituitary sensitivity to ghrelin in postmenopausal women

Kok, Petra; Paulo, Remberto C.; Cosma, Mihaela; Mielke, Kristi L.; Miles, John M.; Bowers, Cyril Y.; Veldhuis, Johannes D.

doi:10.1210/jc.2008-0522

Cited by 35Growth Hormone and Insulin-like Growth FactorsHypothalamic control of reproductive hormonesRegulation of Appetite and Obesity

Estrogen supplementation selectively enhances hypothalamo-pituitary sensitivity to ghrelin in postmenopausal women

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Kok, Petra, Paulo, Remberto C., Cosma, Mihaela, Mielke, Kristi L., Miles, John M., Bowers, Cyril Y., Veldhuis, Johannes D.·2008·The Journal of Clinical Endocrinology & Metabolism

DOI 10.1210/jc.2008-0522PMC PMC2579654

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Abstract

Context: Sex-steroid hormones amplify pulsatile GH secretion by unknown mechanisms. Ghrelin is the most potent natural GH secretagogue discovered to date. A plausible unifying postulate is that estradiol (E2) enhances hypothalamo-pituitary sensitivity to ghrelin (a physiological effect). The hypothesis is relevant to understanding the basis of hyposomatotropism in aging and other relatively hypogonadal states. Objective: Our objective was to test the hypothesis that E2 supplementation potentiates ghrelin’s stimulation of pulsatile GH secretion. Setting: The study was conducted at an academic medical center. Subjects: Healthy postmenopausal women (n = 20) were included in the study. Interventions: Separate-day iv infusions of saline vs. five graded doses of ghrelin were performed in volunteers prospectively randomly assigned to receive (n = 8) or not receive (n = 12) transdermal E2 for 21 d were performed. Measures: GH secretion was estimated by deconvolution analysis and abdominal visceral fat mass determined by computerized axial tomography were calculated. Results: E2 supplementation augmented ghrelin’s stimulation of basal (nonpulsatile) GH secretion by 3.6-fold (P = 0.022), increased GH responses to low-dose ghrelin by 2.9-fold (P = 0.035), did not alter ghrelin efficacy, and elicited more regular patterns of acylated ghrelin concentrations during saline infusion (P = 0.033). Abdominal visceral fat negatively determined responses to ghrelin (R = −0.346; P < 0.005). Conclusions: Transdermal E2 supplementation potentiates GH secretion stimulated by physiological but not pharmacological concentrations of acylated ghrelin, and concomitantly regularizes patterns of bioactive ghrelin secretion in postmenopausal women. Accordingly, the estrogen milieu appears to control sensitivity of the hypothalamopituitary unit to acylated ghrelin.

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In postmenopausal women, oestrogen supplementation enhances hypothalamo-pituitary sensitivity to ghrelin, eliciting a stronger GH response.
“In postmenopausal women oestrogen supplementation enhances the hypothalamo-pituitary sensitivity to ghrelin, thereby eliciting a stronger GH response (Kok et al., 2008).”
From The hypothalamus-pituitary-thyroid (HPT)-axis and its role in physiology and pathophysiology of other hypothalamus-pituitary functions (2021) · cites this paper as Kok et al., 2008

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Norman, C., ROLLENE, N. L., Erickson, D. Z., Miles, J. M., Bowers, C. Y., & Veldhuis, J. D. (2013) · European Journal of Endocrinology · doi:10.1530/eje-13-0733 · Cited by 15 · see citing works
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Short-Term Estradiol Supplementation Augments Growth Hormone (GH) Secretory Responsiveness to Dose-Varying GH-Releasing Peptide Infusions in Healthy Postmenopausal Women
Anderson, S. M., Shah, N., Evans, W. S., Patrie, J. T., Bowers, C. Y., & Veldhuis, J. D. (2001) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.86.2.7240 · Cited by 83 · see citing works
Self-citation
Short-Term Estradiol Supplementation Potentiates Low-Dose Ghrelin Action in the Presence of GHRH or Somatostatin in Older Women
Norman, C., ROLLENE, N. L., Weist, S. M., Wigham, J. R., Erickson, D. Z., Miles, J. M., Bowers, C. Y., & Veldhuis, J. D. (2013) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2013-3043 · Cited by 9 · see citing works
Self-citation
Estro-progestin supplementation enhances the growth hormone secretory responsiveness to ghrelin infusion in postmenopausal women
Villa, P., Costantini, B., Perri, C., Suriano, R., Ricciardi, L., & Lanzone, A. (2007) · Fertility and Sterility · doi:10.1016/j.fertnstert.2007.02.042 · Cited by 16 · see citing works

Authors: Kok, P., Paulo, R. C., Cosma, M., Mielke, K. L., Miles, J. M., Bowers, C. Y., & Veldhuis, J. D.
Affiliations: Mayo Clinic (US)
Tulane University (US)
Corresponding author: Veldhuis, Johannes D.
ORCID: Veldhuis, Johannes D.
Venue: The Journal of Clinical Endocrinology & Metabolism
Publisher: The Endocrine Society
Published: 2008-10-01
Volume: 93
Issue: 10
Pages: 4020-4026
ISSN: 0021-972X (ISSN-L)
1945-7197
DOI: 10.1210/jc.2008-0522
PMC: PMC2579654
OpenAlex: W1996854746
Semantic Scholar: 4fb48efd2f5d560683226819f85829f63dadac74
Cited by: 35
References: 38
Citations by year: 2025: 1 · 2024: 2 · 2023: 1 · 2021: 3 · 2019: 2 · 2017: 3 · 2016: 1 · 2015: 3 · 2014: 1 · 2013: 4 · 2012: 3
FWCI: 2.65
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: U.S. Food and Drug Administration
National Institute on Aging (R01 AG 19695, R01AG029362, R01 AG29362, R01AG019695)
National Center for Research Resources (UL1RR024150)
Topics: Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
Keywords: estrogen supplementation, estradiol, ghrelin, growth hormone secretion, pulsatile GH secretion, postmenopausal women, transdermal estradiol, visceral fat, acylated ghrelin, hyposomatotropism, aging
MeSH terms: Circadian Rhythm, Drug Resistance, Drug Synergism, Estradiol, Female, Follicle Stimulating Hormone, Humans, Hypothalamo-Hypophyseal System, Insulin-Like Growth Factor I, Luteinizing Hormone, Middle Aged, Organ Specificity, Estrogen Replacement Therapy, Postmenopause, Insulin-Like Growth Factor Binding Proteins, Human Growth Hormone, Ghrelin

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Estrogen supplementation selectively enhances hypothalamo-pituitary sensitivity to ghrelin in postmenopausal women

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