Production of erythrogenin by organ cultures of rat kidney.

Organ cultures of rat kidney produce a factor capable of stimulating erythropoiesis in exhypoxic polycythemic mice. This material appears to be renal erythropoietic factor or erythrogenin, since biologic activity was observed only after incubation of the culture media with rat serum. Production of this material was similar in cultures prepared from four different anatomic regions of the kidney, suggesting that erythrogenin may be produced diffusely throughout this organ. Production of erythrogenin was usually insignificant during the first 3 /2 da”s in culture but became significant in all four anatomic regions during the second 31/2 days. Histologic evaluation of the explants revealed primarily autolysis in the early period followed by the development of epithelial elements, many of which comprised renal tubular structures, during the later culture interval. The newly developed cells had a markedly hypertrophic Golgi apparatus, extensive rough-surfaced endoplasmic reticulum, and numerous polyribosomes, findings consistent with active protein synthesis. This organ culture technique provides direct evidence that the kidney produces an erythropoietic factor and represents a promising model for future studies of this problem.