Estrogen induces accumulation of the mitochondrial ribonucleic acid for subunit II of cytochrome oxidase in pituitary tumor cells.
The gene for subunit II of cytochrome oxidase is part of the mitochondrial genome. 17 beta-Estradiol, 1 nM, increased the levels of cytochrome oxidase II mRNA in the GH4C1 pituitary tumor cell line; the increases ranged from 3- to 16-fold over controls in different experiments. Insulin, 300 nM, estradiol, 1 nM, and epidermal growth factor, 10 nM, together caused a larger increase in cytochrome oxidase II mRNA accumulation than did estradiol alone. The dose-response relationship for the induction of cytochrome oxidase II mRNA by estradiol was similar to that for PRL mRNA; maximal induction occurred at about 10(-9) M. This concentration is 10-fold greater than that required for maximal stimulation of cell proliferation and of 1C28, another estrogen-inducible mRNA, indicating that the increase in cytochrome oxidase II mRNA is not a result of increasing the growth rate of the cells. The increase in cytochrome oxidase II mRNA was not caused by an increase in the number of copies of the cytochrome oxidase II gene. Estradiol therefore must induce in the mitochondria an increase in transcription or a decrease in degradation of cytochrome oxidase II mRNA.
Van Itallie
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Yale University School of Medicine, Department of Pharmacology, New Haven, Connecticut 06510.
Dannies
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D000818:Animals; D001483:Base Sequence; D002455:Cell Division / Q000187:drug effects; D004247:DNA / Q000235:genetics; D004274:DNA, Recombinant; D003576:Electron Transport Complex IV / Q000235:genetics*; D004790:Enzyme Induction / Q000187:drug effects; D004815:Epidermal Growth Factor / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D007328:Insulin / Q000494:pharmacology; D008297:Male; D008928:Mitochondria / Q000378:metabolism*; D008969:Molecular Sequence Data; D009693:Nucleic Acid Hybridization; D010911:Pituitary Neoplasms / Q000201:enzymology*; D011388:Prolactin / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis*; D051381:Rats; D011919:Rats, Inbred Strains; D014407:Tumor Cells, Cultured
D004274:DNA, Recombinant; D007328:Insulin; D012333:RNA, Messenger; D004958:Estradiol; D004815:Epidermal Growth Factor; D011388:Prolactin; D004247:DNA; D003576:Electron Transport Complex IV