TY - JOUR
T1 - Tripartite control of growth hormone secretion in women during controlled estradiol repletion
AU - Veldhuis, Johannes D.
AU - Cosma, Mihaela
AU - Erickson, Dana
AU - Paulo, Remberto
AU - Mielke, Kristi
AU - Farhy, Leon S.
AU - Bowers, Cyril Y.
N1 - Funding Information:
This work was supported in part by the General Clinical Research Center Grants MO1 RR00585 from the National Center for Research Resources (Rockville, MD) (to the Mayo Clinic and Foundation) and R01 NIA AG019695, R21 DK072095, DK 063609, and RR019991 from the National Institutes of Health (Bethesda, MD).
PY - 2007/6
Y1 - 2007/6
N2 - Context: 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. Hypothesis: In a controlled estrogenic milieu, near-physiological secretagogue drive will unmask distinct influences of age, AVF, and IGF-I on GH secretion. Location: The study was conducted at an academic medical center. Subjects: Subjects included 10 healthy pre- (PRE) and 10 postmenopausal (POST) women. Procedure: In a defined estradiol (E2) 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). Analysis: 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 E2, 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 ≤ 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 (R2 = 0.46, P = 0.0013), whereas higher IGF-I concentrations forecast increased GHRP-2 and GHRH drive (R 2 ≥ 0.52, P ≤ 0.013). Conclusion: A paradigm of near-physiological secretagogue drive in an E2-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.
AB - Context: 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. Hypothesis: In a controlled estrogenic milieu, near-physiological secretagogue drive will unmask distinct influences of age, AVF, and IGF-I on GH secretion. Location: The study was conducted at an academic medical center. Subjects: Subjects included 10 healthy pre- (PRE) and 10 postmenopausal (POST) women. Procedure: In a defined estradiol (E2) 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). Analysis: 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 E2, 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 ≤ 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 (R2 = 0.46, P = 0.0013), whereas higher IGF-I concentrations forecast increased GHRP-2 and GHRH drive (R 2 ≥ 0.52, P ≤ 0.013). Conclusion: A paradigm of near-physiological secretagogue drive in an E2-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.
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U2 - 10.1210/jc.2007-0043
DO - 10.1210/jc.2007-0043
M3 - Article
C2 - 17405836
AN - SCOPUS:34347207985
SN - 0021-972X
VL - 92
SP - 2336
EP - 2345
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
IS - 6
ER -