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

Abstract

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.

Figure 1

Fasting preinfusion concentrations of total (top) and free (bottom) IGF-I in older men (N = 8) and postmenopausal women (N = 8) pretreated for 10 days with placebo (Pl), estradiol (E₂) or testosterone (Te). Data are the mean ± SEM. The P value reflects the overall interventional effect. Means with unshared (unique) alphabetic superscripts differ significantly (see Results).

Figure 2

Time course of total [Panel A] and free [Panel B] IGF-I concentrations sampled every hour for 2 h before and 6 h during constant iv infusion of saline (50 mL/h) or rh IGF-I (10 μg/kg/h). Measurements were made following randomly ordered supplementation with placebo, estradiol (E₂) or testosterone (Te). Data are the mean ± SEM (N = 8 men and N = 8 women).

Figure 2

Time course of total [Panel A] and free [Panel B] IGF-I concentrations sampled every hour for 2 h before and 6 h during constant iv infusion of saline (50 mL/h) or rh IGF-I (10 μg/kg/h). Measurements were made following randomly ordered supplementation with placebo, estradiol (E₂) or testosterone (Te). Data are the mean ± SEM (N = 8 men and N = 8 women).

Figure 3

Initial rates of rise (slopes) of concentrations of total [top] and free [bottom] IGF-I concentrations over time during saline and rh IGF-I infusion in men and women pretreated with placebo (Pl), testosterone (Te) and estradiol (E₂). Statistical representations are described in Figure 1.

Figure 4

Fasting concentrations of IGFBP-1 [top] and the binary IGF-I/IGFBP-1 complex [bottom] in men and women. See Figure 1 for data format.

Figure 5

Time profiles of IGFBP-1 [Panel A] and binary IGF-I/IGFBP-1 [Panel B] concentrations during continuous iv infusion of saline vs rh IGF-I. Data are presented as described in the legend of Figure 2

Figure 5

Time profiles of IGFBP-1 [Panel A] and binary IGF-I/IGFBP-1 [Panel B] concentrations during continuous iv infusion of saline vs rh IGF-I. Data are presented as described in the legend of Figure 2

Figure 6

Initial rates of rise (slope) of concentrations of IGFBP-1 [top] and binary IGF-I/IGFBP-1 [bottom] in men and women: see legend of Figure 1.