Session: FP01-Cell Specific GH & IGF-1 Signaling
Room 134 (Moscone Center)
Poster Board SAT-109
Hypothesis: GHRH, SST and GHRP jointly determine pulsatile GH secretion in a testosterone (T) modulated manner. The primary hypothesis was that T or estradiol (E2 ) potentiates, whereas BMI attenuates, basal and pulsatile GH production driven by repetitive GHRH pulses and continuous GHRP stimulation .
Design and location: Prospectively randomized, placebo-controlled double-blind cohort study conducted at an academic medical center.
Participants: Twenty-six healthy older men were randomized to testosterone (T) vs placebo supplementation.
Interventions: Pulses of GHRH, SST or saline were infused iv at 90-min intervals for 13 h along with either continuous saline or ghrelin analog (GHRP-2). The train of pulses was followed by a triple stimulus (combined L-arginine, GHRH and GHRP-2) to evoke near-maximal GH secretion over a final 3 h. This design investigates the question how pulsatile GHRH and SST signals interact with nearly continuous GHRP stimulation. Because testosterone (T), estradiol (E2) and relative adiposity (BMI, body mass index) influence GH output, a corollary issue is how sex-steroids and BMI tune GH responses to defined multipeptide interactions. To create a graded range of systemic T (and E2) concentrations, healthy older men were pretreated with either im saline (placebo) or T before the peptide-infusion studies. This strategy allowed stepwise regression of basal and pulsatile GH secretion measures on T, E2 and BMI.
Results: Testosterone vs placebo supplementation doubled pulsatile GH secretion during GHRH/saline pulses. Pulsatile GH secretion correlated positively with T concentrations (270-1170 ng/dL) in the 26 men during saline/saline (P=0.015, R2=0.24), GHRH/saline pulses (P=0.020, R2=0.22), and combined GHRH/GHRP-2 (P=0.016, R2=0.25) infusions. Basal GH secretion correlated with T during GHRP-2/saline drive (P=0.020, R2=0.16). In contrast, pulsatile GH secretion varied negatively with BMI during saline/GHRP-2 infusion (P=0.001, R2=0.36), as well as after the triple stimulus preceded by GHRH/GHRP-2 (P=0.013, R2=0.23). Mean (10-h) GH concentrations under GHRP-2 were predicted jointly by estradiol [positively] and BMI [negatively] (P<0.001, R2=0.520).
Conclusions: Estradiol, T and BMI selectively control secretagogue-specific GH-regulatory mechanisms in older men.
Nothing to Disclose: CN, CB, JDV
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