Tripartite control of growth hormone secretion in women during controlled estradiol repletion.
BACKGROUND
Studies of how aging attenuates GH secretion are confounded by differences in sex-steroid milieus, abdominal visceral fat mass (AVF), and IGF-I concentrations and limited in interpretability by the use of pharmacological doses of secretagogues.


OBJECTIVE
In a controlled estrogenic milieu, near-physiological secretagogue drive will unmask distinct influences of age, AVF, and IGF-I on GH secretion.


METHODS
The study was conducted at an academic medical center.


METHODS
Subjects included 10 healthy pre- (PRE) and 10 postmenopausal (POST) women.


METHODS
In a defined estradiol (E(2)) milieu, we compared GH secretion after submaximal stimulation with GH-releasing peptide (GHRP)-2 (ghrelin analog), GHRH, and l-arginine (an inhibitor of somatostatin outflow).


METHODS
We related GH responses to age stratum (dichotomous variable) and AVF and IGF-I concentrations (continuous variables).


RESULTS
In the face of comparable concentrations of E(2), testosterone, and SHBG: 1) age (P < 0.001) and secretagogue type (P < 0.001) independently determined GH secretion; 2) GH responses in POST subjects were only 26-33% of those in PRE (P < or = 0.002) across all secretagogues; 3) POST women lost the PRE order of secretagogue potency (GHRP-2 > GHRH = l-arginine); and 4) in the combined cohorts, higher AVF predicted reduced l-arginine-stimulated GH secretion (R(2) = 0.46, P = 0.0013), whereas higher IGF-I concentrations forecast increased GHRP-2 and GHRH drive (R(2) > or = 0.52, P < or = 0.013).


CONCLUSIONS
A paradigm of near-physiological secretagogue drive in an E(2)-clamped milieu unmasks tripartite deficits in peptide-signaling pathways in healthy POST, compared with PRE, women. Post hoc analyses indicate that both greater visceral adiposity and lower IGF-I concentrations mark this triple regulatory defect.
Veldhuis
Johannes D
JD
Endocrine Research Unit 9, General Clinical Research Center, Mayo Medical and Graduate Schools of Medicine, Mayo Clinic, Rochester, MN 55905, USA. veldhuis.johannes@mayo.edu
Cosma
Mihaela
M
Erickson
Dana
D
Paulo
Remberto
R
Mielke
Kristi
K
Farhy
Leon S
LS
Bowers
Cyril Y
CY
D000328:Adult; D000368:Aged; D000375:Aging / Q000378:metabolism*; D001120:Arginine / Q000008:administration & dosage; D004958:Estradiol / Q000008:administration & dosage*; D005260:Female; D013007:Growth Hormone-Releasing Hormone / Q000008:administration & dosage; D019382:Human Growth Hormone / Q000097:blood* / Q000378:metabolism; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008875:Middle Aged; D009842:Oligopeptides / Q000008:administration & dosage; D017698:Postmenopause / Q000378:metabolism*; D017697:Premenopause / Q000378:metabolism*
D009842:Oligopeptides; D019382:Human Growth Hormone; D004958:Estradiol; D007334:Insulin-Like Growth Factor I; D013007:Growth Hormone-Releasing Hormone; D001120:Arginine; C091874:growth hormone-releasing peptide-2