Estradiol supplementation in postmenopausal women attenuates suppression of pulsatile growth hormone secretion by recombinant human insulin-like growth factor type I

Johannes D. Veldhuis, Daniel M. Keenan, Joy N. Bailey, Adenborduin Adeniji, John M. Miles, Remberto Paulo, Mihaela Cosma, Cacia Soares-Welch

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

Background: Why pulsatile GH secretion declines in estrogen-deficient postmenopausal individuals remains unknown. One possibility is that estrogen not only enhances stimulation by secretagogues but also attenuates negative feedback by systemic IGF-I. Site: The study took place at an academic medical center. Subjects: Subjects were healthy postmenopausal women (n = 25). Methods: The study included randomized assignment to estradiol (n = 13) or placebo (n = 12) administration for 16 d and randomly ordered administration of 0, 1.0, 1.5, and 2.0 mg/m2 recombinant human IGF-I sc on separate days fasting. Analysis: Deconvolution analysis of pulsatile and basal GH secretion and approximate entropy (pattern-regularity) analysis were done to quantify feedback effects of IGF-I. Outcomes: Recombinant human IGF-I injections increased mean and peak serum IGF-I concentrations dose dependently (P < 0.001) and suppressed mean GH concentrations (P < 0.001), pulsatile GH secretion (P = 0.001), and approximate entropy (P < 0.001). Decreased GH secretion was due to reduced secretory-burst mass (P = 0.005) and frequency (P < 0.001) but not basal GH release (P = 0.52). Estradiol supplementation lowered endogenous, but did not alter infused, IGF-I concentrations while elevating mean GH concentrations (P = 0.012) and stimulating pulsatile (P = 0.008) and basal (P < 0.001) GH secretion. Estrogen attenuated IGF-I's inhibition of pulsatile GH secretion (P = 0.042) but was unable to restore physiological GH pulse frequency or normalize approximate entropy. Conclusion: Short-term estrogen replacement in postmenopausal women selectively mutes IGF-Imediated feedback on pulsatile GH secretion. Disinhibition of negative feedback thus confers a novel mechanism by which estrogen may obviate hyposomatotropism.

Original languageEnglish (US)
Pages (from-to)4471-4478
Number of pages8
JournalJournal of Clinical Endocrinology and Metabolism
Volume93
Issue number11
DOIs
StatePublished - Nov 2008

ASJC Scopus subject areas

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

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