DISCORDANCE OF SERUM AND TISSUE SOMATOMEDIN LEVELS IN GROWTH HORMONE-STIMULATED GROWTH IN THE RAT

Although the somatomedins are believed to mediate GH-induced somatic growth, circulating levels of insulin-like growth factor I (IGF-I) do not always correlate with growth rate. To evaluate a paracrine or autocrine effect that might explain this discordance, the concentrations of plasma and tissue IGF-I were compared with indices of growth in hypophysectomized rats treated with rat GH (rGH). The rats received a total of 250 .mu.g rGH by either continuous pump infusion (P) or twice daily injections (I). After 4 days of treatment, the amounts of IGF-I present in acetic acid extracts of liver and kidney and in native serum were determined by RIA and related to proximal tibial epiphyseal plate width. Tibial epiphyseal plate width increased from 198 .+-. 6 .mu.m (mean .+-. SE) in untreated controls to 339 .+-. 13 .mu.m in group P and 347 .+-. 9 .mu.m in group I; weight gain was 11.6 .+-. 1.0 g in group P and 9.6 .+-. 0.8 g in group I, while control animals lost 1.0 g. Serum concentrations of IGF-I were no different between control animals and those in the injection group (0.91 .+-. 0.06 vs. 0.90 .+-. 0.06 U/ml), whereas levels in the infusion group increased slightly (1.1 .+-. 0.05 U/ml). In contrast rGH administration caused tissue IGF-I to double in liver (control, 0.24 .+-. 0.04 U/g; P, 0.51 .+-. 0.03 U/g; I, 0.46 .+-. 0.05 U/g) and nearly triple in kidney (control, 0.52 .+-. 0.05 U/g; P, 1.51 .+-. 0.09 U/g; I, 1.36 .+-. 0.08 U/g). There was no detectable change in somatomedin-binding protein by gel exclusion chromatography. Since the rGH administered was sufficient to stimulate growth and increase tissue somatomedin levels without corresponding increases in circulating IGF-I, an autocrine or paracrine action of IGF-I appears to mediate GH''s initial somatogenic actions in the young rat.