Determinants of dual secretagogue drive of burst-like growth hormone secretion in premenopausal women studied under a selective estradiol clamp.
The present study tests the hypothesis that estradiol (E(2)), 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 addback of E(2) 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 E(2)-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). E(2) 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, E(2) availability, and intraabdominal adiposity. Moreover, the rapidity of GH release is controlled 2-fold jointly by E(2) and GHRH.
Erickson
Dana
D
Endocrine Research Unit, Department of Internal Medicine, Mayo School of Graduate Medical Education, General Clinical Research Center, Mayo Clinic, Rochester, Minnesota 55905, USA.
Keenan
Daniel M
DM
Farhy
Leon
L
Mielke
Kristi
K
Bowers
Cyril Y
CY
Veldhuis
Johannes D
JD
D000279:Administration, Cutaneous; D000328:Adult; D004703:Endocrine System / Q000187:drug effects / Q000378:metabolism; D004958:Estradiol / Q000008:administration & dosage* / Q000097:blood; D005260:Female; D013007:Growth Hormone-Releasing Hormone / Q000378:metabolism; D019382:Human Growth Hormone / Q000097:blood* / Q000378:metabolism*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D017697:Premenopause / Q000378:metabolism*; D011673:Pulsatile Flow
D019382:Human Growth Hormone; D004958:Estradiol; D007334:Insulin-Like Growth Factor I; D013007:Growth Hormone-Releasing Hormone