Estradiol supplementation modulates growth hormone (GH) secretory-burst waveform and recombinant human insulin-like growth factor-I-enforced suppression of endogenously driven GH release in postmenopausal women

The present study tests the mechanistic postulate that estrogen confers resistance to negative feedback by systemic IGF-I. To this end, eight postmenopausal women received a constant iv infusion of recombinant human (rh)IGF-I (10 μg/kg·h x 6 h) and saline in randomized order on the 10th day of supplementation with oral estradiol (E₂) and placebo (Pl). GH secretion was quantitated by 10-mm blood sampling, immunochemiluminometry assay, and deconvolution analysis. Administration of E₂ compared with Pl followed by saline infusion: 1) stimulated pulsatile GH secretion (μg/liter-6 h), viz., 12 ± 3.3 (Pl) and 18 ± 4.6 (E₂) (mean ± SEM, paired comparison, P < 0.05); 2) halved the time latency (min) to achieve peak GH secretion after GHRH injection, 24 ± 2.2 (Pl) and 12 ± 2.1 (E₂) (P < 0.01); and 3) did not alter the mass of GH secreted (μg/ liter) in response to a maximally effective dose of GHRH, 30 ± 7.2 (Pl) and 37 ± 11 (E₂). Exposure to E₂ compared with Pl followed by rhIGF-I infusion: 1) accelerated the rate of decline of GH concentrations by 3.3-fold, viz., absolute slope (μg/liter-1000 min), 3.8 (range, 2.5-5.0) (Pl) and 12 (range, 10-14) (E₂) (P < 0.001); 2) augmented the algebraic decrement in GH concentrations (μg/liter) enforced by rhIGF-I infusion, 0.73 ± 0.21 (Pl) and 1.6 ± 0.25 (E₂) (P < 0.01); 3) halved the time delay (min) to peak GHRH-induced GH secretion, 20 ± 1.2 (Pl) vs. 10 ± 1.3 (E₂) min (P < 0.01). In contradistinction, E₂ did not alter: 1) the capability of rhIGF-I to suppress GHRH-stimulated GH secretory burst mass significantly, viz., by 50 ± 8% (Pl) and 52 ± 14% (E₂) (P < 0.05 each vs. saline); 2) the hourly rate of rise of infused (total) IGF-I concentrations; and 3) total and ultrafiltratably free IGF-I concentrations (μg/liter) attained at the end of the two rhIGF-I infusions. In summary, compared with Pl, E₂ supplementation in postmenopausal women: 1) amplifies endogenously driven GH secretory-burst mass; 2) initiates rapid onset of GHRH-stimulated GH release; and 3) potentiates IGF-I-dependent suppression of unstimulated GH concentrations. Based upon companion modeling data, we postulate that E₂ facilitates the upstroke and IGF-I enforces the downstroke of high-amplitude GH secretory bursts in estrogen-replete individuals.