The Serum Half-Life of Somatomedin Activity: Evidence for Growth Hormone Dependence

Abstract

The serum half-life of somatomedin (SM) activity has been measured following the intravenous injection of SM activity into hypophysectomized rats. A [3H]thymidine incorporation assay in chick embryo fibroblasts (CEFs) has been utilized to measure SM activity. Cell cycle analysis data obtained with the flow microfluorometer shows that the [3H]thymidine incorporation data reflects actual DNA synthesis. When normal rat serum was injected, a half-life for SM activity of approximately 3 h was determined. In marked contrast, when serum from hypophysectomized (hypox) rats acutely treated with growth hormone (GH) was used as the source of SM actively, the half-life of the SM actively was short, approximately 8 min. However, when serum from hypox rats chronically treated with GH was injected, the half-life was again long, approximately 4 h. SM activity has been separated from its binding proteins by boiling under acid conditions or chromatography on Sephadex G-50 in 1 n acetic acid. The halflife of this partially purified SM activity was short, in the range of 10–30 min. Finally, recombination of the partially purified SM activity with the large proteins in normal serum extended the half-life of the SM from 10–30 min to about 2 h. These data indicate that the serum half-life of SM activity is GH dependent and suggest that the serum binding protein, like SM itself, is under GH control.

Production of immunoreactive insulin-like growth factor-I (IGF-I) and IGF-I binding proteins by human lung tumours

“…The apparently elevated levels of IGF-I in the unextracted sera of cancer patients were clearly due to BP effects as evidenced by the detection of IGF-I binding proteins in cancer patient serum fractions having reactivity in the Amersham RIA and by the results obtained for extracted sera. The observation that serum levels of IGF-I are not increased in SCLC patients, though consistent with those of earlier reports (Minuto et al, 1986;Macaulay et al, 1988b), is perhaps surprising given the over-production of BPs in lung cancer patients and the ability of BPs to prolong the half life of IGFs in the circulation (Cohen & Nissley, 1976;Zapf et al, 1979). One explanation is that the release of IGF-I from SCLC cells in vivo is, like IGF-I release from liver, hormonally regulated by mechanisms which do not exist in vitro.…”

Genetic and environmental components of interindividual variation in circulating levels of IGF-I, IGF-II, IGFBP-1, and IGFBP-3.

“…This is not unexpected since the three traits are interrelated and a linear correlation has been reported between the sum of concentrations of IGF-I and IGF-II, and IGFBP-3 (21). Classically serum IGFBP-3 levels are known to vary according to growth hormone secretion (24). Other factors influencing the circulating IGFBP-3 level include age, pubertal development, nutrition, and hepatic function (21).…”

Increased Levels of IGF-I and IGFBP-3 in Synovial Fluids of Patients with Rheumatoid Arthritis

“…We have found that the IGF-I levels in normal synovial fluid were about one-tenth of those in normal adult human serum, reported to be 176 ± 49 ng/ml [6] and that IGF-I levels in synovial fluid from patients with RA were much higher than those in normal samples, suggesting that local regulation of IGF-I may occur in synovial fluid. IGFBP-3 is known to be the most abundant IGFBP in serum, forming a ternary complex (150 kDa), that serves as the major circulating carrier of the IGFs and increases the half-life of the IGFs in the circulation [7]. In contrast to serum, the 42-39 kDa doublet (IGFBP-3) was low in normal synovial fluid, and a prominent immunoreactive 30 kDa IGFBP-3 fragment was detected by Western immunoblot analysis.…”