Context: GH-releasing peptide (GHRP), GHRH, and somatostatin are physiological regulators of pulsatile GH secretion. Hypothesis: Age, independently of abdominal visceral fat (AVF) and basal (nonpulsatile) GH secretion, damps pulsatile GH secretion driven by physiological (rather than pharmacological) amounts of GHRP and GHRH in an experimentally controlled estradiol (E2) milieu. Design and Setting: A prospectively randomized, double-blind parallel-cohort study was conducted at an academic medical center. Participants: Community-dwelling healthy premenopausal (PRE, age 24 ± 0.8 yr, n = 20) and postmenopausal (POST, age 63 ± 1.8 yr, n = 22) women participated in the study. Interventions: Gonadal-axis down-regulation with leuprolide was followed by randomized add-back of placebo or transdermal E2 and separate-day iv bolus injections of a half-maximally stimulatory dose of GHRP-2 or GHRH (each 0.33 μg/kg). Analysis: Three-way analysis of covariance included main factors age, E 2 status, and secretagogue type and covariates AVF and basal GH secretion. Results: Submaximally stimulated pulsatile GH secretion was positively determined by PRE vs. POST age (P<0.001), E2 repletion vs. depletion (P = 0.001) and GHRP-2 vs. GHRH stimulation (P<0.001), after adjustment for AVF and basal secretion. E2 vs. placebo elevated fasting mean GH concentrations in both PRE and POST women (P = 0.006) but increased basal (nonpulsatile) GH secretion in PRE only (P = 0.002). PRE vs. POST age prolonged GHRH-driven GH secretory bursts by 36% (P = 0.006). Conclusion: PRE vs. POST age, E2 availability, and physiological peptide drive are triple determinants of pulsatile GH secretion independently of abdominal visceral fat and nonpulsatile GH secretion in healthy women.
ASJC Scopus subject areas
- Endocrinology, Diabetes and Metabolism
- Clinical Biochemistry
- Biochemistry, medical