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Submitted on April 18, 2005
Accepted on August 1, 2005
Endocrine Research Unit, Department of Internal Medicine, Mayo School of Graduate Medical Education, General Clinical Research Center, Mayo Clinic, Rochester, MN 55905; Department of Internal Medicine; Department of Statistics, University of Virginia, Charlottesville, VA 22904-4135; Department of Medicine, Tulane University Health Sciences Center, New Orleans, LA 70112
* To whom correspondence should be addressed. E-mail: veldhuis.johannes{at}mayo.edu.
Background. Aging, body composition and sex steroids jointly determine GH production. However, the actions of any given factor are confounded by 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 [PRE and POST] underwent GnRH agonist-induced downregulation 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, POST compared with PRE women exhibited: (i) lower concentrations of IGF-I (P = 0.028) and GH (P < 0.05); (ii) reduced pulsatile but elevated basal GH secretion (P < 0.05); (iii) more irregular GH patterns (P = 0.027); (iv) an attenuated GH response to simultaneous GHRH/GHRP-2 stimulation (P < 0.01); and (v) more rapid onset of GH release within secretory bursts (P < 0.01). In contrast, AVF negatively forecast GH responses to L-arginine/GHRP-2 (R2 = 0.45, P < 0.001) and L-arginine/GHRH (R2 = 0.57, P = 0.007). From these marked contrasts, model-based 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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