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.
BACKGROUND
GH-releasing peptide (GHRP), GHRH, and somatostatin are physiological regulators of pulsatile GH secretion.


OBJECTIVE
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.


METHODS
A prospectively randomized, double-blind parallel-cohort study was conducted at an academic medical center.


METHODS
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.


METHODS
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).


METHODS
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).


CONCLUSIONS
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.
Hudson
Susan B
SB
Department of Obstetrics and Gynecology, Mayo School of Graduate Medical Education, Clinical Translational Research Center, Mayo Clinic, Rochester, Minnesota 55905.
Schroeder
Darrell R
DR
Bailey
Joy N
JN
Mielke
Kristi L
KL
Erickson
Dana
D
Miles
John M
JM
Bowers
Cyril Y
CY
Veldhuis
Johannes D
JD
D000328:Adult; D000367:Age Factors; D000368:Aged; D015331:Cohort Studies; D003940:Diagnostic Techniques, Endocrine; D004311:Double-Blind Method; D004958:Estradiol / Q000008:administration & dosage* / Q000097:blood; D005260:Female; D013007:Growth Hormone-Releasing Hormone / Q000008:administration & dosage* / Q000819:agonists; D006262:Health; D019382:Human Growth Hormone / Q000097:blood / Q000378:metabolism*; D006801:Humans; D008875:Middle Aged; D009842:Oligopeptides / Q000008:administration & dosage*; D010919:Placebos; D017698:Postmenopause / Q000097:blood / Q000187:drug effects / Q000502:physiology; D017697:Premenopause / Q000097:blood / Q000187:drug effects / Q000502:physiology; D011673:Pulsatile Flow / Q000187:drug effects; D012107:Research Design; D055815:Young Adult
D009842:Oligopeptides; D010919:Placebos; D019382:Human Growth Hormone; D004958:Estradiol; D013007:Growth Hormone-Releasing Hormone; C091874:growth hormone-releasing peptide-2