TY - JOUR
T1 - Distinctive inhibitory mechanisms of age and relative visceral adiposity on growth hormone secretion in pre- and postmenopausal women studied under a hypogonadal clamp
AU - Veldhuis, Johannes D.
AU - Erickson, Dana
AU - Mielke, Kristi
AU - Farhy, Leon S.
AU - Keenan, Daniel M.
AU - Bowers, Cyril Y.
PY - 2005/11
Y1 - 2005/11
N2 - 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.
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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U2 - 10.1210/jc.2005-0854
DO - 10.1210/jc.2005-0854
M3 - Article
C2 - 16091485
AN - SCOPUS:27744552856
SN - 0021-972X
VL - 90
SP - 6006
EP - 6013
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
IS - 11
ER -