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.

Effects of oral versus transdermal estradiol plus micronized progesterone on thyroid hormones, hepatic proteins, lipids, and quality of life in menopausal women with hypothyroidism: a clinical trial

“…Oral estrogen causes an increased sensitivity of the pituitary to growth hormone releasing hormone stimulation but a reduced peripheral responsiveness to GH. Thus, despite an increase in bioavailable GH, there is a decreased hepatic responsiveness to produce IGF-1 29 . On the other hand, IGF-1 concentrations did not differ in response to transdermal estradiol use in postmenopausal women 30,31 …”

“…Thus, despite an increase in bioavailable GH, there is a decreased hepatic responsiveness to produce IGF-1. 29 On the other hand, IGF-1 concentrations did not differ in response to transdermal estradiol use in postmenopausal women. 30,31 The effects of different progestogens on hepatic proteins are less known.…”

Gender determines ACTH recovery from hypercortisolemia in healthy older humans

“…All samples from a given subject were assayed in the same batch. Sex steroids were assayed by mass spectrometry, and LH, FSH, TSH and prolactin by immuno-chemiluminescence [24,25]. …”

Regulated recovery of pulsatile growth hormone secretion from negative feedback: a preclinical investigation

“…Twenty-five healthy older adults participated (n ϭ 14 men, n ϭ 11 women) after providing written informed consent, and the protocol was approved by the Mayo Institutional Review Board. Data from two subsets of subjects were evaluated earlier in relation to the recovery of algebraic nadir and peak GH concentrations and of approximate entropy (ApEn) during saline and two-peptide infusion (45,46). Deconvolution analyses were performed here for the first time.…”