Studies on the mechanism of compensatory renal hypertrophy and hyperplasia in a nephrectomized animal model. I. Evidence for a renotropic growth stimulating factor in uninephrectomized rabbit sera using tissue culture.

When synchronized primary rabbit kidney confluent monolayer cell cultures were incubated with a medium that contained uninephrectomized rabbit serum, the incorporation of tritiated thymidine into DNA was much greater than that with a medium that contained normal rabbit serum. The maximal growth stimulating activity of uninephrectomized serum on thymidine incorporation into sparsely cultured cells was increased approximately 5 fold above that of normal serum. We conclude that uninephrectomized sera contain a growth stimulating factor. Uninephrectomized rabbit sera showed no increased stimulation of DNA synthesis in primary rabbit skin cultured cells above that by normal rabbit serum, indicating that the growth stimulating factor in uninephrectomized serum shows renotropic specificity in tissue culture. A transformed rabbit kidney cell line RK-13 did not respond to the renotropic growth stimulating factor. However, primary and the transformed rabbit kidney cells absorbed the renotropic growth stimulating factor from uninephrectomized sera. Thus, the cell line RK-13 has receptors for adsorption of the renotropic growth factor but is unable to respond further to the growth stimulating process. The renotropic growth stimulating factor is heat unstable and undialyzable by dialysis tubings with pore size up to 12,000 molecular weight. Thus the renotropic growth factor seems to be a macromolecule, probably a protein.