Effect of activins AB and B on DNA synthesis stimulated by epidermal growth factor in primary cultured rat hepatocytes.
The effect of activins AB and B on DNA synthesis stimulated by epidermal growth factor (EGF) was studied in primary cultured rat hepatocytes and compared with the effect of activin A, a suppressor of DNA synthesis. Activin AB inhibited DNA synthesis as assessed by [3H]thymidine incorporation. The inhibition by activin AB was detected at 6 ng/ml, and the 12.5 ng/ml concentration produced almost maximal inhibition, approximately 40%, almost the same as that produced by activin A. Inhibition by activin A was detected at 3 ng/ml, and the 6 ng/ml concentration produced almost maximal inhibition. Activin B, on the other hand, had no effect on DNA synthesis up to 50 ng/ml. The increase in labeling index by EGF was also reduced to about 20% by 25 ng/ml activin A and activin AB, but not by activin B. Activin B, however, inhibited the binding of [125I]activin A to hepatocytes, but had no effect on the inhibition of DNA synthesis by activin A, even at 3-fold excess concentrations. These findings suggest that activin AB may act in the same manner as activin A does in terms EGF's inhibitory effect on DNA synthesis, although the effective concentration is higher than that of activin A. The findings also suggest that activin B receptors are present in hepatocytes but that they do not mediate signal transduction leading to the inhibition of DNA synthesis.
Niimi
Shingo
S
Division of Biological Chemistry and Biologicals, National Institute of Health Sciences, Tokyo, Japan. niimi@nihs.go.jp
Horikawa
Mai
M
Seki
Taiichiro
T
Ariga
Toyohiko
T
Kobayashi
Tetsu
T
Hayakawa
Takao
T
D000818:Animals; D002478:Cells, Cultured; D004247:DNA / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism*; D028322:Inhibin-beta Subunits / Q000494:pharmacology* / Q000502:physiology; D008297:Male; D051381:Rats; D017208:Rats, Wistar
C498906:Inhbb protein, rat; C103008:inhibin beta A subunit; D004815:Epidermal Growth Factor; D004247:DNA; D028322:Inhibin-beta Subunits