Testosterone and Estradiol Regulate Free Insulin-Like Growth Factor I (IGF-I), IGF Binding Protein 1 (IGFBP-1), and Dimeric IGF-I/IGFBP-1 Concentrations

• Published in: The journal of clinical endocrinology and metabolism 2005-05, Vol.90 (5), p.2941-2947
• Main Authors: Veldhuis, Johannes D., Frystyk, Jan, Iranmanesh, Ali, Ørskov, Hans
• Format: Article
• Language: English
• Subjects: Aged; Biological and medical sciences; Cross-Over Studies; Dimerization; Endocrinopathies; Estradiol - pharmacology; Female; Fundamental and applied biological sciences. Psychology; Humans; Insulin-Like Growth Factor Binding Protein 1; Insulin-Like Growth Factor Binding Proteins - blood; Insulin-Like Growth Factor Binding Proteins - chemistry; Insulin-Like Growth Factor I - analysis; Insulin-Like Growth Factor I - chemistry; Male; Medical sciences; Middle Aged; Pregnancy Proteins - blood; Pregnancy Proteins - chemistry; Prospective Studies; Testosterone - pharmacology; Vertebrates: endocrinology
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.2004-1314

The present study tests the clinical postulate that elevated testosterone (Te) and estradiol (E2) concentrations modulate the effects of constant iv infusion of saline vs. recombinant human IGF-I on free IGF-I, IGF binding protein (IGFBP)-1, and dimeric IGF-I/IGFBP-1 concentrations in healthy aging adults. To this end, comparisons were made after administration of placebo (Pl) vs. Te in eight older men (aged 61 ± 4 yr) and after Pl vs. E2 in eight postmenopausal women (62 ± 3 yr). In the saline session, E2 lowered and Te increased total IGF-I; E2 specifically elevated IGFBP-1 by 1.5-fold and suppressed free IGF-I by 34%; and E2 increased binary IGF-I/IGFBP-1 by 5-fold more than Te. During IGF-I infusion, the following were found: 1) total and free IGF-I rose 1.4- to 2.0-fold (Pl) and 2.1–2.5-fold (Te) more rapidly in men than women; 2) binary IGF-I/IGFBP-1 increased 3.4-fold more rapidly in men (Te) than women (E2); and 3) end-infusion free IGF-I was 1.6-fold higher in men than women. In summary, E2, compared with Te supplementation, lowers concentrations of total and ultrafiltratably free IGF-I and elevates those of IGFBP-1 and binary IGF-I/IGFBP-1, thus putatively limiting IGF-I bioavailability. If free IGF-I mediates certain biological actions, then exogenous Te and E2 may modulate the tissue effects of total IGF-I concentrations unequally.