Increased Levels of Multiplication-Stimulating Activity, an Insulin-Like Growth Factor, in Fetal Rat Serum

Multiplication-stimulating activity (MSA), purified from medium conditioned by the BRL-3A rat liver cell line, previously has been shown to be closely related to the human somatomedins or insulin-like growth factors. A radioimmunoassay was utilized to measure MSA levels in sera from fetal, maternal, and young rats. A serum somatomedin-binding protein was found to interfere in the radioimmunoassay by competing with antibody for binding125I-labeled MSA. Therefore, prior to radioimmunoassay, sera were filtered on Sephadex G-75 in 1 M acetic acid to dissociate and separate somatomedin activity from the binding protein. Concentrations of MSA by radioimmunoassay were 20- to 100-fold higher in fetal rat sera (1.8-4.4 μ g/ml) than in maternal sera. MSA levels gradually decreased after birth, reaching maternal levels by day 25 of extrauterine life. MSA concentrations in fetal rat sera also were found to be correspondingly high by a rat liver membrane radioreceptor assay and a competitive binding protein assay using rat serum somatomedin-binding protein. The findings of higher levels of MSA in fetal than in maternal rat sera and the gradual decline in MSA serum concentrations after birth are in direct contrast to total somatomedin activities measured by bioassay. Thus, MSA may function as a growth factor in the fetal rat whereas other somatomedins may play a role in stimulating growth during extrauterine life.