TY - JOUR
T1 - Pre- versus postmenopausal age, estradiol, and peptide-secretagogue type determine pulsatile growth hormone secretion in healthy women
T2 - Studies using submaximal agonist drive and an estrogen clamp
AU - Hudson, Susan B.
AU - Schroeder, Darrell R.
AU - Bailey, Joy N.
AU - Mielke, Kristi L.
AU - Erickson, Dana
AU - Miles, John M.
AU - Bowers, Cyril Y.
AU - Veldhuis, Johannes D.
N1 - Funding Information:
This work was supported in part by the Clinical Translational Research Center Grant MO1 RR00585 to the Mayo Clinic and Foundation from the National Center for Research Resources (Rockville, MD) and R01 NIA AG29362 from the National Institutes of Health (Bethesda, MD).
PY - 2010/1
Y1 - 2010/1
N2 - 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.
AB - 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.
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U2 - 10.1210/jc.2009-1769
DO - 10.1210/jc.2009-1769
M3 - Article
C2 - 19858315
AN - SCOPUS:75149186448
SN - 0021-972X
VL - 95
SP - 353
EP - 360
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
IS - 1
ER -