Estradiol regulates GH-releasing peptide's interactions with GH-releasing hormone and somatostatin in postmenopausal women

Abstract

ObjectiveEstrogen stimulates pulsatile secretion of GH, via mechanisms that are largely unknown. An untested hypothesis is that estradiol (E2) drives GH secretion by amplifying interactions among GH-releasing hormone (GHRH), somatostatin (SS), and GH-releasing peptide (GHRP).DesignThe design comprised double-blind randomized prospective administration of transdermal E2vs placebo to healthy postmenopausal women (n=24) followed by pulsatile GHRH or SS infusions for 13 h overnight with or without continuous GHRP2 stimulation.MethodsEnd points were mean concentrations, deconvolved secretion, and approximate entropy (ApEn; a regularity measure) of GH.ResultsBy generalized ANOVA models, it was observed that E2vs placebo supplementation: i) augmented mean (13-h) GH concentrations (P=0.023), GHRH-induced pulsatile GH secretion over the first 3 h (P=0.0085) and pulsatile GH secretion over the next 10 h (P=0.054); ii) increased GHRP-modulated (P=0.022) and SS-modulated (P<0.001) GH ApEn; and iii) did not amplify GHRH/GHRP synergy during pulsatile GH secretion. By linear regression, E2concentrations were found to be positively correlated with GH secretion during GHRP2 infusion (P=0.022), whereas BMI was found to be negatively correlated with GH secretion during GHRH (P=0.006) and combined GHRH/GHRP (P=0.015) stimulation. E2and BMI jointly determined triple (combinedl-arginine, GHRH, and GHRP2) stimulation of GH secretion after saline (R2=0.44 andP=0.003) and pulsatile GHRH (R2=0.39 andP=0.013) infusions.ConclusionIn summary, in postmenopausal women, E2supplementation augments the amount (mass) and alters the pattern (regularity) of GH secretion via interactions among GHRH, SS, GHRP, and BMI. These outcomes introduce a more complex model of E2supplementation in coordinating GH secretion in aging women.