Gender, sex-steroid, and secretagogue-selective recovery from growth hormone-induced feedback in older women and men

Context: GH negatively regulates its own secretion. How gender, sex steroids, and secretagogues modulate GH autofeedback is not known. Hypothesis/Objective: Supplementation with sex steroids and/or a peptidyl secretagogue will enhance the escape of GH from autoinhibition, thus framing a mechanism for amplifying pulsatile GH secretion. Subjects and Setting: Ten healthy postmenopausal women and 10 comparably aged men participated at the Clinical-Translational Science Unit. Design/Interventions: Randomly ordered, double-blind, prospective crossover treatment with placebo vs. testosterone (men) or placebo vs. estradiol (women). Autofeedback was imposed by an iv pulse of GH. Recovery of feedback inhibition was quantified during constant infusion of saline, GHRH, or GH-releasing peptide-2 (three peptide categories). Outcomes/Results: During negative feedback, total (integrated) GH recovery depended upon gender (P = 0.017), sex hormone (P < 0.001), and peptide category (P < 0.001). Mechanistic analysis revealed that feedback-suppressed nadir GH concentrations were determined by sex-steroid treatment (P = 0.018) but not by gender (P = 0.444). Peak GH escape was controlled by both treatment (P = 0.004) and gender (P = 0.003). Nadir GH and peak GH during feedback were enhanced by GHRH or GHRP-2 (P < 0.001 for both). Gender x peptide (P = 0.012 for nadir GH), treatment x peptide (P < 0.001 total and peak GH), and gender x treatment (P = 0.017 nadir GH) regulated GH recovery interactively. Conclusion: Gender, sex-steroid supplementation, and secretagogue type confer distinct feedback-rescuing effects, introducing a new level of complexity in the control of pulsatile GH regulation.