The effect of epidermal growth factor and IGF-I infusion on hepatic and renal expression of the IGF-system in adult female rats.
Systemic administration of epidermal growth factor (EGF) in neonatal rats results in reduced body weight gain and decreased circulating levels of IGF-I, suggesting its involvement in EGF-induced growth retardation. We investigated the effect of EGF and/or IGF-I administration for 7 days on circulating IGF-I and IGFBP levels and hepatic and renal IGF-system mRNA expression profiles in adult female rats. EGF administration (30 microg/rat/day) did not influence body weight, liver or kidney weight. In contrast, IGF-I (400 microg/rat/day) and EGF/IGF-I administration increased both body weight and kidney weight. Also, serum IGF-I and the 30 kDa IGFBPs (IGFBP-1 and -2) were significantly increased in these groups. Serum IGFBP-3 levels increased in the IGF-I group along with increased hepatic IGFBP-1 and -3 mRNA levels. In contrast, in the EGF administration group serum IGFBP-3 levels were significantly decreased; however, the mRNA levels remained unchanged. In the EGF/IGF-I administration group, serum IGF-I and IGFBP-3 levels were significantly lowered when compared with the IGF-I administration group. This was in contrast to the effect on kidney weight increase that was identical for the IGF-I and EGF/IGF-I groups. The decrease in serum IGFBP-3 was not reflected at the hepatic IGFBP-3 mRNA level. IGFBP-3 expression might be regulated at a post-transcriptional level although EGF induced IGFBP-3 proteolysis could not be demonstrated in vitro. We conclude that EGF administration reduced serum IGFBP-3 whereas IGF-I administration increased the level of IGFBP-3 and IGF-I and resulted in an increased body and kidney weight in adult female rats.
van Neck
J W
JW
Laboratory of Pediatrics, Subdivision of Pediatric Endocrinology, Erasmus University/Sophia Children's Hospital, Rotterdam, The Netherlands. vanneck@kgk.fgg.eur.nl
Berghout
E M
EM
Vinter-Jensen
L
L
Groffen
C A
CA
Cingel
V
V
Dits
N F
NF
Drop
S L
SL
Flyvbjerg
A
A
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D005260:Female; D018969:Insulin-Like Growth Factor Binding Proteins / Q000097:blood / Q000187:drug effects*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D018969:Insulin-Like Growth Factor Binding Proteins; D012333:RNA, Messenger; D004815:Epidermal Growth Factor; D007334:Insulin-Like Growth Factor I