Growth hormone regulates the rodent hepatic epidermal growth factor receptor at a pretranslational level.
Recent studies have implicated the involvement of pituitary factor(s) in the regulation of hepatic epidermal growth factor receptor (EGF-R) levels. In the present study the possible role of GH as a regulator of EGF-R has been examined by measuring hepatic EGF-R mRNA and EGF binding in intact and GH-deficient rats and mice before and after administration of GH. Using a human EGF-R probe, 10.5 and 6.0 kb transcripts were detected in mouse and rat liver by Northern gel analysis. EGF-R mRNA was quantified by solution hybridization, and EGF binding determined by incubation of 125I-labelled EGF with a low-density membrane fraction. Levels of hepatic EGF-R mRNA and binding of EGF in female rats were about two-thirds of those in male rats. GH-deficient (lit/lit) male and female mice had approximately 10 and 25% respectively of the levels of EGF-R mRNA and EGF binding of intact male and female mice. Furthermore, hypophysectomized rats exhibited a reduced level of EGF-R mRNA and EGF binding, corresponding to about 20% of the levels detected in intact male rats. When hypophysectomized male and female rats received recombinant human GH (hGH) either as intermittent injections or by continuous infusion using osmotic minipumps, the EGF-R mRNA and EGF binding levels increased to about half those of the intact male animals. No differences between intermittent or continuous administration of hGH on the induction of EGF-R mRNA or EGF binding could be seen.(ABSTRACT TRUNCATED AT 250 WORDS)
Johansson
S
S
Department of Pathology, Karolinska Institute, Huddinge University Hospital, Sweden.
Husman
B
B
Norstedt
G
G
Andersson
G
G
D000818:Animals; D015152:Blotting, Northern; D004815:Epidermal Growth Factor / Q000378:metabolism; D066246:ErbB Receptors / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D005838:Genotype; D013006:Growth Hormone / Q000494:pharmacology / Q000502:physiology*; D006801:Humans; D007016:Hypophysectomy; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D008970:Molecular Weight; D009154:Mutation; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011981:Receptors, Prolactin / Q000378:metabolism; D014158:Transcription, Genetic
D012333:RNA, Messenger; D011981:Receptors, Prolactin; D004815:Epidermal Growth Factor; D013006:Growth Hormone; D066246:ErbB Receptors