Pre- versus postmenopausal age, estradiol, and peptide-secretagogue type
determine pulsatile growth hormone secretion in healthy women: studies using
submaximal agonist drive and an estrogen clamp.
Author(s): Hudson SB, Schroeder DR, Bailey JN, Mielke KL, Erickson D, Miles JM, Bowers CY,
Veldhuis JD.
Affiliation(s): Department of Obstetrics and Gynecology, Mayo School of Graduate Medical
Education, Clinical Translational Research Center, Mayo Clinic, Rochester,
Minnesota 55905.
Publication date & source: 2010, J Clin Endocrinol Metab. , 95(1):353-60
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 (E(2)) 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 addback of placebo or transdermal E(2) and separate-day iv bolus
injections of a half-maximally stimulatory dose of GHRP-2 or GHRH (each 0.33
mug/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), E(2) repletion vs. depletion (P = 0.001) and
GHRP-2 vs. GHRH stimulation (P < 0.001), after adjustment for AVF and basal
secretion. E(2) 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, E(2) availability, and physiological peptide drive
are triple determinants of pulsatile GH secretion independently of abdominal
visceral fat and nonpulsatile GH secretion in healthy women.
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