Expression of insulin-like growth factor I in cultured rat hepatocytes: effects of insulin and growth hormone.
The effects of GH and insulin the accumulation of insulin-like growth factor I (IGF-I) RNA transcripts and the secretion of immunoreactive IGF-I protein were studied in rat liver hepatocytes cultured in serum-free medium. GH at concentrations of 10 ng/ml or greater stimulated the accumulation of IGF-I RNA transcripts relative to actin transcripts in poly(A)+ RNA isolated from cultured hepatocytes. The time course of IGF-I transcript accumulation in response to GH appeared to be biphasic. The transcript levels rose dramatically during the first 2 h after exposure of the cultures to GH, declined between 3 and 6 h, but reaccumulated by 24 h after exposure to GH. The presence of insulin did not influence the effect of GH on the accumulation of IGF-I RNA transcripts, although insulin did elevate IGF-I transcript levels in the absence of GH. Analysis of RNA pulse-labeled with thiouridine followed by purification of the thiol-labeled RNA using mercurated agarose indicated that GH probably acts by increasing IGF-I transcription. Insulin also affected the release of immunoreactive IGF-I into the culture medium. In the presence of insulin, immunoreactive IGF-I accumulated in the culture medium to approximately the same extent over a 24-h period regardless of whether GH was also present. In the absence of insulin, immunoreactive IGF-I accumulated in the medium only if GH was present. The results suggest that insulin may play an important role in both IGF-I transcript accumulation and the secretion of IGF-I from cultured hepatocytes.
Johnson
T R
TR
Department of Developmental Genetics and Anatomy, School of Medicine, Case Western Reserve University, Cleveland, Ohio 44106.
Blossey
B K
BK
Denko
C W
CW
Ilan
J
J
D000818:Animals; D002478:Cells, Cultured; D005260:Female; D013006:Growth Hormone / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000235:genetics*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D011863:Radioimmunoassay; D051381:Rats; D011920:Rats, Inbred WF; D013002:Somatomedins / Q000235:genetics*; D014158:Transcription, Genetic / Q000187:drug effects
D007328:Insulin; D012333:RNA, Messenger; D013002:Somatomedins; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone