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Estradiol Supplementation in Postmenopausal Women Attenuates Suppression of Pulsatile Growth Hormone Secretion by Recombinant Human Insulin-like Growth Factor Type I

Departments of Medicine (J.D.V., J.N.B., A.A., J.M.M., M.C., C.S.-W.) and Pediatrics (R.P.) Endocrine Research Unit, Mayo School of Graduate Medical Education, Clinical Translational Science Center, Mayo Clinic, Rochester, Minnesota 55905; and Department of Statistics (D.M.K.), University of Virginia, Charlottesville, Virginia 22904

Address all correspondence and requests for reprints to: Johannes D. Veldhuis, Departments of Medicine, Mayo School of Graduate Medical Education, Clinical Translational Science Center, Mayo Clinic, Rochester, Minnesota 55905. E-mail: veldhuis.johannes{at}mayo.edu.

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-I-mediated feedback on pulsatile GH secretion. Disinhibition of negative feedback thus confers a novel mechanism by which estrogen may obviate hyposomatotropism.

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