Glucocorticoid regulation of metallothionein during murine development.
During the second half of gestation in the mouse there is a rise in both fetal (4-fold) and maternal (10-fold) metallothionein-I (MT-I) mRNA in the liver (but not in the kidney). There is a large increase in plasma corticosterone (the predominant murine glucocorticoid hormone), as well as an increase in hepatic zinc, which is coincident with the induction of MT-I mRNA. Considering that both of these compounds are known to be effective inducers of MT-I mRNA, we set out to determine whether either one or both were involved in the developmental regulation of MT-I genes. Several lines of evidence suggest that corticosterone is the principal inducer of fetal MT-I mRNA: The induction of MT-I mRNA in the liver, but not in the kidney, mimics glucocorticoid regulation but not metal regulation. Reduction of maternal corticosterone levels by treating mice with metyrapone lowered MT-I mRNA levels but had no effect on zinc levels. A line of transgenic mice carrying a metallothionein-growth hormone fusion gene that is responsive to metals but unresponsive to glucocorticoids was not developmentally regulated. Based on these observations, we propose that corticosterone is responsible for the induction of MT-I mRNA and that the resulting MT sequesters zinc and copper which may be used later in development.
D000818:Animals; D002712:Chlorides / Q000494:pharmacology; D003345:Corticosterone / Q000502:physiology; D003907:Dexamethasone / Q000494:pharmacology; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism; D005796:Genes; D005938:Glucocorticoids / Q000502:physiology*; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000196:embryology; D007668:Kidney / Q000196:embryology / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000196:embryology* / Q000378:metabolism; D008668:Metallothionein / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D011247:Pregnancy; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism*; D013270:Stomach / Q000196:embryology; D014018:Tissue Distribution; D015032:Zinc / Q000494:pharmacology; D017967:Zinc Compounds
D002712:Chlorides; D005938:Glucocorticoids; D012333:RNA, Messenger; D017967:Zinc Compounds; D003907:Dexamethasone; C016837:zinc chloride; D008668:Metallothionein; D015032:Zinc; D003345:Corticosterone