Proliferation-related responses in rat astrocytes to epidermal growth factor

The signals which regulate the proliferation of astrocytes have relevance to both normal developmental processes and abnormal states of gliosis or glial tumor formation. We have extended studies of astrocyte proliferation and related responses in primary cultures of rat telencephalic cortical astrocytes as a result of treatment with epidermal growth factor. Epidermal growth factor stimulates the rate of DNA synthesis five fold and maintains the rate of protein synthesis. The stimulation occurs at a dose of 2 ng/ml and is greater in higher density cultures than in lower density cultures, perhaps representing a relative starvation for the growth factor. The astrocyte response is still present even after being cultured 3 1/2 weeks in serum-free and non-growth factor or hormone-supplemented media. Combined immunofluorescence and thymidine autoradiography disclose that glial fibrillary acidic protein containing cells are the cells synthesizing DNA in response to the growth factor, and combined rhodamine and fluorescein-linked stains disclose that epidermal growth factor is in the glial fibrillary acidic protein containing cells. Proliferation-related 2-deoxyglucose uptake is stimulated at approximately the same dose as DNA synthesis is stimulated, but the time course is relatively slow, maximizing at 48 hr. Ornithine decarboxylase is stimulated in 6 hr indicating more rapid nuclear stimulation by the signal. In conclusion, epidermal growth factor has a clear direct interaction with glial fibrillary acidic protein-containing cells which is greater in higher density cultures, is still present in long-quiescent cells, and includes DNA synthesis, cell cycle progression, hexose uptake, and polyamine synthesis.