Regulation of human growth hormone receptor gene expression by human growth hormone in a human hepatoma cell line.
We have investigated the effects of recombinant human growth hormone (r-hGH) on the expression of hGH-receptor in a human hepatoma cell line (HuH 7). Levels of hGH-receptor mRNA in HuH 7 cells treated with different doses of r-hGH were measured by means of an RNase protection assay. Treatment with r-hGH at physiological concentrations (12.5, 25 and 50 ng/ml) resulted in an increase in hGH-receptor mRNA levels within 1 h of addition of the hormone. A steady state was reached after 3-4 h and maintained for at least 48 h. In contrast, treatment with supraphysiological r-hGH concentrations (150 and 500 ng/ml) led to a down-regulation of hGH-receptor mRNA levels during the first 3 h after hormone addition followed by an increase in hGH-receptor mRNA levels thereafter. Nuclear run-off assays demonstrated that these changes in hGH-receptor mRNA levels were a result of changes in the rate of transcription of the hGH-receptor gene. Cycloheximide (10 micrograms/ml) did not affect these changes in hGH-receptor gene transcription significantly, indicating that they are mediated by pre-existing factors and do not require new protein synthesis. These data demonstrate that r-hGH specifically regulates the rate of transcription of the hGH-receptor gene in a human hepatoma cell line.
Mullis
P E
PE
Department of Biochemistry, University College and Middlesex School of Medicine, London, U.K.
Lund
T
T
Patel
M S
MS
Brook
C G
CG
Brickell
P M
PM
D015152:Blotting, Northern; D006528:Carcinoma, Hepatocellular; D005786:Gene Expression Regulation; D013006:Growth Hormone / Q000502:physiology; D006801:Humans; D007700:Kinetics; D008113:Liver Neoplasms; D012333:RNA, Messenger / Q000378:metabolism; D011986:Receptors, Somatotropin / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
D012333:RNA, Messenger; D011986:Receptors, Somatotropin; D013006:Growth Hormone