Tripartite control of growth hormone secretion in women during controlled estradiol repletion

Johannes D. Veldhuis, Mihaela Cosma, Dana Erickson, Remberto Paulo, Kristi Mielke, Leon S. Farhy, Cyril Y. Bowers

Research output: Contribution to journalArticlepeer-review

5 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)2336-2345
Number of pages10
JournalJournal of Clinical Endocrinology and Metabolism
Issue number6
StatePublished - Jun 2007

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical


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