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

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, 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.