TY - JOUR
T1 - Determinants of dual secretagogue drive of burst-like growth hormone secretion in premenopausal women studied under a selective estradiol clamp
AU - Erickson, Dana
AU - Keenan, Daniel M.
AU - Farhy, Leon
AU - Mielke, Kristi
AU - Bowers, Cyril Y.
AU - Veldhuis, Johannes D.
PY - 2005/3
Y1 - 2005/3
N2 - The present study tests the hypothesis that estradiol (E2), compared with placebo (Pl), amplifies combined-secretagogue stimulation of GH secretion in premenopausal women studied at comparable IGF-I and testosterone concentrations. To this end, 13 women underwent GnRH agonist-induced gonadal down-regulation followed by graded transdermal add-back of E2 or Pl and randomly ordered iv infusions of saline or paired secretagogues on separate morning fasting. GH secretion was assessed by frequent blood sampling, immunochemiluminometry, and variable-waveform deconvolution analysis. Two-way ANOVA revealed that specific secretagogue combination (P < 0.001), E 2 status (P = 0.012), and their interaction (P = 0.038) jointly determined GH secretory-burst mass. Compared with Pl, the E2-clamped milieu elevated mean fasting GH concentrations (P = 0.032), the mass of GH secreted in bursts (P = 0.037), and maximal stimulation by paired L-arginine/GH-releasing peptide (GHRP)-2 (P = 0.028). E2 also markedly accelerated the initial release of GH induced by GHRH/GHRP-2 (P < 0.001) and L-arginine/GHRH (P < 0.01). By linear regression analysis, E 2 concentrations positively forecast 41% of intersubject variability in GH secretion stimulated by combined L-arginine/GHRP-2 (P = 0.018), whereas abdominal visceral-fat mass negatively predicted 49% of that due to L-arginine/GHRH (P = 0.012). These data indicate that pulsatile GH secretion in young women studied at constant IGF-I and testosterone concentrations is dictated 3-fold jointly by secretagogue pair, E2 availability, and intraabdominal adiposity. Moreover, the rapidity of GH release is controlled 2-fold jointly by E2 and GHRH.
AB - The present study tests the hypothesis that estradiol (E2), compared with placebo (Pl), amplifies combined-secretagogue stimulation of GH secretion in premenopausal women studied at comparable IGF-I and testosterone concentrations. To this end, 13 women underwent GnRH agonist-induced gonadal down-regulation followed by graded transdermal add-back of E2 or Pl and randomly ordered iv infusions of saline or paired secretagogues on separate morning fasting. GH secretion was assessed by frequent blood sampling, immunochemiluminometry, and variable-waveform deconvolution analysis. Two-way ANOVA revealed that specific secretagogue combination (P < 0.001), E 2 status (P = 0.012), and their interaction (P = 0.038) jointly determined GH secretory-burst mass. Compared with Pl, the E2-clamped milieu elevated mean fasting GH concentrations (P = 0.032), the mass of GH secreted in bursts (P = 0.037), and maximal stimulation by paired L-arginine/GH-releasing peptide (GHRP)-2 (P = 0.028). E2 also markedly accelerated the initial release of GH induced by GHRH/GHRP-2 (P < 0.001) and L-arginine/GHRH (P < 0.01). By linear regression analysis, E 2 concentrations positively forecast 41% of intersubject variability in GH secretion stimulated by combined L-arginine/GHRP-2 (P = 0.018), whereas abdominal visceral-fat mass negatively predicted 49% of that due to L-arginine/GHRH (P = 0.012). These data indicate that pulsatile GH secretion in young women studied at constant IGF-I and testosterone concentrations is dictated 3-fold jointly by secretagogue pair, E2 availability, and intraabdominal adiposity. Moreover, the rapidity of GH release is controlled 2-fold jointly by E2 and GHRH.
UR - http://www.scopus.com/inward/record.url?scp=15944368604&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=15944368604&partnerID=8YFLogxK
U2 - 10.1210/jc.2004-1621
DO - 10.1210/jc.2004-1621
M3 - Article
C2 - 15613434
AN - SCOPUS:15944368604
SN - 0021-972X
VL - 90
SP - 1741
EP - 1751
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
IS - 3
ER -