Distinctive inhibitory mechanisms of age and relative visceral adiposity on growth hormone secretion in pre- and postmenopausal women studied under a hypogonadal clamp

Johannes D Veldhuis, Dana Erickson, Kristi Mielke, Leon S. Farhy, Daniel M. Keenan, Cyril Y. Bowers

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Background: Aging, body composition, and sex steroids jointly determine GH production. However, the actions of any given factor are confounded by the effects of the other two. Hypothesis: Age and abdominal visceral fat (AVF) mass govern GH secretion via individually distinctive mechanisms, which can be unmasked by short-term sex steroid deprivation. Design/Subjects: In a university setting, healthy pre- and postmenopausal volunteers underwent GnRH agonist-induced down-regulation for 6 wk to deplete ovarian sex steroids. GH secretion was evaluated by frequent blood sampling, saline vs. dual secretagogue infusions, an irregularity statistic, variable waveform deconvolution analysis, and a simplified feedback model. Computerized tomography was used to estimate AVF mass. Outcomes/Measures: In the sex steroid-deficient milieu, postmenopausal compared with premenopausal women exhibited 1) lower concentrations of IGF-I (P = 0.028) and GH (P < 0.05); 2) reduced pulsatile, but elevated basal, GH secretion (P < 0.05); 3) more irregular GH patterns (P = 0.027); 4) an attenuated GH response to simultaneous GHRH/GH-releasing peptide-2 stimulation (P < 0.01); and 5) more rapid onset of GH release within secretory bursts (P < 0.01). In contrast, AVF negatively forecast GH responses to L-arginine/GH-releasing peptide-2 (r2 = 0.45; P < 0.001) and L-arginine/GHRH (r2 = 0.57; P < 0.007). From these marked contrasts, modelbased analyses predicted distinguishable mechanisms by which aging and AVF alter pulsatile GH production. Conclusion: Under limited confounding by sex steroids, age and body composition modulate GH secretion via highly selective peptidyl pathways in healthy women.

Original languageEnglish (US)
Pages (from-to)6006-6013
Number of pages8
JournalJournal of Clinical Endocrinology and Metabolism
Volume90
Issue number11
DOIs
StatePublished - Nov 2005

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Adiposity
Clamping devices
Intra-Abdominal Fat
Growth Hormone
Steroids
Fats
Body Composition
Arginine
Aging of materials
Peptides
Computerized tomography
Deconvolution
Chemical analysis
Insulin-Like Growth Factor I
Gonadotropin-Releasing Hormone
Volunteers
Blood
Down-Regulation
Tomography
Outcome Assessment (Health Care)

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

Cite this

Distinctive inhibitory mechanisms of age and relative visceral adiposity on growth hormone secretion in pre- and postmenopausal women studied under a hypogonadal clamp. / Veldhuis, Johannes D; Erickson, Dana; Mielke, Kristi; Farhy, Leon S.; Keenan, Daniel M.; Bowers, Cyril Y.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 90, No. 11, 11.2005, p. 6006-6013.

Research output: Contribution to journalArticle

Veldhuis, Johannes D ; Erickson, Dana ; Mielke, Kristi ; Farhy, Leon S. ; Keenan, Daniel M. ; Bowers, Cyril Y. / Distinctive inhibitory mechanisms of age and relative visceral adiposity on growth hormone secretion in pre- and postmenopausal women studied under a hypogonadal clamp. In: Journal of Clinical Endocrinology and Metabolism. 2005 ; Vol. 90, No. 11. pp. 6006-6013.
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AU - Bowers, Cyril Y.

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AB - Background: Aging, body composition, and sex steroids jointly determine GH production. However, the actions of any given factor are confounded by the effects of the other two. Hypothesis: Age and abdominal visceral fat (AVF) mass govern GH secretion via individually distinctive mechanisms, which can be unmasked by short-term sex steroid deprivation. Design/Subjects: In a university setting, healthy pre- and postmenopausal volunteers underwent GnRH agonist-induced down-regulation for 6 wk to deplete ovarian sex steroids. GH secretion was evaluated by frequent blood sampling, saline vs. dual secretagogue infusions, an irregularity statistic, variable waveform deconvolution analysis, and a simplified feedback model. Computerized tomography was used to estimate AVF mass. Outcomes/Measures: In the sex steroid-deficient milieu, postmenopausal compared with premenopausal women exhibited 1) lower concentrations of IGF-I (P = 0.028) and GH (P < 0.05); 2) reduced pulsatile, but elevated basal, GH secretion (P < 0.05); 3) more irregular GH patterns (P = 0.027); 4) an attenuated GH response to simultaneous GHRH/GH-releasing peptide-2 stimulation (P < 0.01); and 5) more rapid onset of GH release within secretory bursts (P < 0.01). In contrast, AVF negatively forecast GH responses to L-arginine/GH-releasing peptide-2 (r2 = 0.45; P < 0.001) and L-arginine/GHRH (r2 = 0.57; P < 0.007). From these marked contrasts, modelbased analyses predicted distinguishable mechanisms by which aging and AVF alter pulsatile GH production. Conclusion: Under limited confounding by sex steroids, age and body composition modulate GH secretion via highly selective peptidyl pathways in healthy women.

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