Developmental changes in tissue and plasma concentrations of the biologically active species of nerve growth factor in the mouse, by using a two-site radioimmunoassay.

A sensitive and specific radioimmunoassay has been developed for the biologically active beta-subunit of the mouse submaxillary-gland nerve-growth-factor protein. This assay is based on the ;two-site' radioimmunoassay method of Addison & Hales (1971), and a detailed description of the experimental method is given. The assay is readily adaptable for the rapid assay of nerve growth factor in partially purified preparations, or can be used as a sensitive method for measuring the low tissue concentrations of this protein, measurement of concentrations as low as 0.25ng/ml in plasma or tissue extracts being possible. This assay was used to determine tissue concentrations of nerve growth factor in adult mice and developmental changes in its content in various tissues. There were significant sex differences in the nerve-growth-factor content of submaxillary glands, plasma and sympathetic ganglia, with males having higher concentrations, whereas the concentrations in all other tissues measured showed no significant difference between male and female animals. The changes in plasma concentration of the factor during development parallel the changes observed in the submaxillary gland, and it was suggested that plasma nerve growth factor may be derived mainly from this source. Circulating nerve growth factor appears to be specifically concentrated in sympathetic ganglia. There is a relatively high concentration of the factor in neonatal ganglia and plasma, and it is suggested that this may be derived from maternal sources.