Regulation of pituitary insulin-like growth factor-I messenger ribonucleic acid levels in rats harboring somatomammotropic tumors: implications for growth hormone autoregulation.
Insulin-like growth factor-I (IGF-I) is produced in multiple tissues and is believed to exert its action in a paracrine or autocrine fashion. We have investigated the GH dependency of tissue IGF-I gene expression in rats harboring implanted somatomammotropic tumors. Circulating GH and radioimmunoassayable IGF-I levels were markedly elevated in these animals. Hepatic IGF-I messenger RNA (mRNA) transcripts were induced about 5-fold in the tumor-bearing rats relative to control animals, and about 50-fold relative to the hypophysectomized liver IGF-I mRNA. IGF-I mRNA content was also modestly induced in the heart, muscle, and kidney of the tumor-bearing animals. IGF-I mRNA transcripts of 8.0, 6.2, 3.8, 2.4, 1.3, and 1.0 kilobases were markedly stimulated in the pituitaries of the GH-tumor bearing rats relative to control pituitaries. Pituitary IGF-I mRNA induction was maximal between 2 and 6 weeks after tumor implantation, a time at which circulating GH levels were also increasing sharply. As previously reported, pituitary GH mRNA was inhibited in tumor-bearing rats. The stimulation of pituitary IGF-I gene expression in these animals, therefore, appears to be dependent on circulating, and not local, pituitary GH concentrations. These data support the GH dependency of pituitary IGF-I gene expression. IGF-I is known to decrease GH production in vitro. High circulating levels of IGF-I present in these animals may account for the observed inhibition of GH gene expression. These data raise the alternative possibility that induction of locally produced IGF-I may contribute to this phenomenon.
Fagin
J A
JA
Department of Medicine, University of California Los Angeles School of Medicine 90048.
Brown
A
A
Melmed
S
S
D000818:Animals; D003001:Cloning, Molecular; D004247:DNA / Q000235:genetics; D005796:Genes; D013006:Growth Hormone / Q000097:blood; D006706:Homeostasis; D007016:Hypophysectomy; D007334:Insulin-Like Growth Factor I / Q000235:genetics*; D010902:Pituitary Gland / Q000378:metabolism*; D010911:Pituitary Neoplasms / Q000503:physiopathology*; D012333:RNA, Messenger / Q000235:genetics*; D051381:Rats; D011920:Rats, Inbred WF; D013002:Somatomedins / Q000235:genetics*; D014158:Transcription, Genetic
D012333:RNA, Messenger; D013002:Somatomedins; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D004247:DNA