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Research was conducted to investigate the effects of saline versus insulin-like growth factor-I (IGF-I) administration on serum levels of free and total IGF-I, IGFBP-1 and IGF binding protein-3 (IGFBP-3). A monoclonal noncompetitive time-resolved immunofluorometric assay was utilized to measure IGF-I while linear correlations between serum free IGF-I and IGFBP-1 were performed on log-transformed data. Results indicated that IGFBP-1 is a major in vivo regulator of serum free IGF-I.

The present study was designed as a randomized, double-blind placebo (Plc)-controlled study to determine the effect of 2 wk of growth hormone administration (GH-adm.) on energy expenditure (EE) and substrate oxidation in healthy humans. Sixteen young healthy men were divided into two groups. The study consisted of two 24-h measurements (indirect calorimetry), separated by 2 wk of either Plc or GH injections (6 IU/day). At baseline, no significant differences were observed between the two groups in any of the measured anthropometric, hormonal, or metabolic parameters, neither did the parameters change over time in the Plc group. GH-adm. resulted in a 4.4% increase in 24-h EE (P < 0.05) and an increase in fat oxidation by 29% (P < 0.05). However, a decrease in the respiratory quotient was only observed in the postabsorptive phase after an overnight fast (0.84 +/- 0.1 to 0.79 +/- 0.1, P < 0.05). Furthermore, lean body mass (LBM) was increased by GH-adm. only [62.8 +/- 2.5 kg (baseline) vs. 64.7 +/- 2.4 kg (after), P < 0.001]. In conclusion, GH-adm. increases 24-h EE, which may be partly explained by increased LBM. Furthermore, GH-adm. stimulates fat combustion, especially in the postabsorptive state.

At present, the circulating bioactivity of insulin-like growth factor I (IGF-I) is estimated by immunological measurements of IGF-I levels. However, immunoassays ignore the modifying effects of the IGF-binding proteins (IGFBPs) on the interaction between IGF-I and the IGF-I receptor (IGF-IR). Therefore, we developed an IGF-I kinase receptor activation assay (KIRA) based on cells transfected with the human IGF-IR gene. The bioassay was sensitive (detection limit 0.08 microg/l), specific (cross-reactivity of insulin, insulin analogs, and proinsulin was <1%; IGF-II cross-reactivity was 12%), and accurate (within- and between-assay coefficients of variation <7 and <15%). The operational range of the assay (0.25-10.0 microg/l) allowed for determination of IGF-I bioactivity in serum from patients with, for example, growth hormone deficiency, type 1 diabetes, and acromegaly. Addition of IGFBPs dose dependently reduced the KIRA signal, whereas addition of IGF-II to preformed complexes (1:1 molar ratio) of IGF-I and IGFBP dose dependently increased IGF-I bioactivity by displacement of bound IGF-I. In conclusion, the KIRA will enable us to compare IGF-I bioactivity with existing immunological measurements of IGF-I in serum and, hopefully, to elucidate the factors that determine IGF-I bioactivity in vivo.

The bioactivity of the growth hormone-insulin-like growth factor (IGF) system is reduced in Turner syndrome and may explain the reduction seen in final height. We compared levels of free and total IGF-I, immunoreactive and Western ligand blot IGF-binding protein (IGFBP)-3, and IGFBP-3 proteolysis in women with Turner syndrome (n = 23) before (T(B)) and during 6 mo treatment with 17beta-estradiol and norethisterone. An age-matched group of controls (n = 24) was included. Total IGF-I and immunoreactive levels of IGFBP-3 were comparable in T(B) and controls, whereas free IGF-I (P = 0.02) in T(B) was less than in controls. Western ligand blotting (WLB)-IGFBP-3 was significantly lower in T(B) than in controls (P = 0.0005). Accordingly, IGFBP-3 proteolysis was greater in Turner syndrome (P = 0.001). Female sex steroid treatment increased WLB-IGFBP-3 (P = 0.0005), whereas immunoreactive IGFBP-3 and IGFBP-3 proteolysis were normalized (P = 0.004). Free IGF-I remained unchanged (P = 0.8), with a tendency toward a decrease in total IGF-I (P = 0.1). In conclusion, despite normal total IGF-I and immunoreactive IGFBP-3, free serum IGF-I is less and IGFBP-3 proteolysis is greater in Turner syndrome than in controls. During sex steroid treatment, IGFBP-3 proteolysis normalized, without any change in free IGF-I.

K(+)-deficient rats and control rats were injected for 16 days with saline or human growth hormone (hGH, 200 micrograms/day). hGH treatment of K(+)-deficient rats resulted in increased weight gain and soleus muscle weight. Extensor digitorum longus (EDL) muscle weight and tail and tibia length were unchanged. In control rats, hGH induced an increase in all weight and length parameters. K+ deficiency was associated with reduced serum insulin-like growth factor I (IGF-I) and serum insulin but unchanged total 3,5,3'-triiodothyronine (TT3) and total thyroxine. hGH treatment of the K(+)-deficient rats restored serum IGF-I, but not serum insulin, and decreased TT3. In saline-treated K(+)-deficient rats [3H]ouabain binding site concentration decreased by 44 and 39% in soleus and EDL muscle, respectively, as compared with the saline-treated controls. hGH had no effect on the [3H]ouabain binding site concentration in the K(+)-deficient group, but, in control rats, increases of 11 and 8% were observed in soleus and EDL muscle, respectively. When the increase in muscle weight was taken into account, this amounted to relative increases of 24 and 30%, respectively. Low circulating GH and IGF-I levels are not the sole explanation for the growth retardation in K+ deficiency. GH/IGF-I stimulate the synthesis of Na(+)-K+ pumps in rats with an otherwise normal hormonal status.