title: Complex regulation of GH autofeedback under dual-peptide drive: studies under a pharmacological GH and sex steroid clamp.
abstract: To test the postulate that sex difference, sex steroids, and peptidyl secretagogues control GH autofeedback, 11 healthy postmenopausal women and 14 older men were each given 1) a single iv pulse of GH to enforce negative feedback and 2) continuous iv infusion of saline vs. combined GHRH/GHRP-2 to drive feedback escape during pharmacological estradiol (E(2); women) or testosterone (T; men) supplementation vs. placebo in a double-blind, prospectively randomized crossover design. By three-way ANCOVA, sex difference, sex hormone treatment, peptide stimulation, and placebo/saline responses (covariate) controlled total (integrated) GH recovery during feedback (each P < 0.001). Both sex steroid milieu (P = 0.019) and dual-peptide stimulation (P < 0.001) determined nadir (maximally feedback-suppressed) GH concentrations. E(2)/T exposure elevated nadir GH concentrations during saline infusion (P = 0.003), whereas dual-peptide infusion did so independently of T/E(2) and sex difference (P = 0.001). All three of sex difference (P = 0.001), sex steroid treatment (P = 0.005), and double-peptide stimulation (P < 0.001) augmented recovery of peak (maximally feedback-escaped) GH concentrations. Peak GH responses to dual-peptidyl agonists were greater in women than in men (P = 0.016). E(2)/T augmented peak GH recovery during saline infusion (P < 0.001). Approximate entropy analysis corroborated independent effects of sex steroid treatment (P = 0.012) and peptide infusion (P < 0.001) on GH regularity. In summary, sex difference, sex steroid supplementation, and combined peptide drive influence nadir, peak, and entropic measurements of GH release under controlled negative feedback. To the degree that the pharmacological sex steroid, GH, and dual-peptide clamps provide prephysiological regulatory insights, these outcomes suggest major determinants of pulsatile GH secretion in the feedback domain.
authors.affiliation: Endocrine Research Unit, Mayo School of Graduate Medical Education, Center for Translational Science Activities, MayoClinic, Rochester, MN 55905, USA. veldhuis.johannes@mayo.edu
authors.forename: Johannes D
authors.initials: JD
authors.lastname: Veldhuis
authors.forename: Dana
authors.initials: D
authors.lastname: Erickson
authors.forename: John M
authors.initials: JM
authors.lastname: Miles
authors.forename: Cyril Y
authors.initials: CY
authors.lastname: Bowers
mesh_terms: D000368:Aged; D015992:Body Mass Index; D004311:Double-Blind Method; D004958:Estradiol / Q000097:blood; D025461:Feedback, Physiological / Q000502:physiology*; D005260:Female; D012739:Gonadal Steroid Hormones / Q000494:pharmacology*; D007987:Gonadotropin-Releasing Hormone / Q000494:pharmacology; D019382:Human Growth Hormone / Q000502:physiology*; D006801:Humans; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000494:pharmacology; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000494:pharmacology; D012727:Sex Characteristics; D012738:Sex Hormone-Binding Globulin / Q000494:pharmacology; D053719:Tandem Mass Spectrometry; D013739:Testosterone / Q000097:blood / Q000494:pharmacology
chemical_list: D012739:Gonadal Steroid Hormones; D018970:Insulin-Like Growth Factor Binding Protein 1; D018972:Insulin-Like Growth Factor Binding Protein 3; D009842:Oligopeptides; D012738:Sex Hormone-Binding Globulin; D019382:Human Growth Hormone; D007987:Gonadotropin-Releasing Hormone; D013739:Testosterone; D004958:Estradiol; D007334:Insulin-Like Growth Factor I; C091874:growth hormone-releasing peptide-2