Dual effects of glucagon and cyclic amp on dna synthesis in cultured rat hepatocytes: Stimulatory regulation in early G1 and inhibition shortly before the s phase entry
✍ Scribed by G. Hege Thoresen; Tor-Erik Sand; Magne Refsnes; Olav F. Dajani; Tormod K. Guren; Ivar P. Gladhaug; Anne Killi; Thoralf Christoffersen
- Publisher
- John Wiley and Sons
- Year
- 1990
- Tongue
- English
- Weight
- 964 KB
- Volume
- 144
- Category
- Article
- ISSN
- 0021-9541
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✦ Synopsis
Blindern, N-0316 0 t h 3 , Norway Although several lines of evidence implicate cyclic AMP in the humoral control of liver growth, its precise role is still not clear. To explore further the role of cyclic AMP in hepatocyte proliferation, we have examined the effects of glucagon and other cyclic AMP-elevating agents on the DNA synthesis in primary cultures of adult rat hepatocytes, with particular focus on the temporal aspects. The cells were cultured in a serum-free, defined medium and treated with epidermal growth factor (EGF), insulin, and dexamethasone. Exposure of the hepatocytes to low concentrations (10 pM-1 nM) of glucagon in the early stages of culturing (usually within 6 h from plating) enhanced the initial rate of S phase entry without affecting the lag time from the plating to the onset of DNA synthesis, whereas higher concentrations inhibited it. In contrast, glucagon addition at later stages