Down-regulation of the mdr gene by thyroid hormone during Xenopus laevis development.
The developmental regulation of mdr in Xenopus laevis has been investigated. Xe-mdr expression was first detected in the early tadpole stage just prior to the onset of feeding and increased during intestinal development, with a sharp decline at metamorphosis. Xe-mdr expression was found to be localized specifically to the epithelial cells lining the intestinal tract. When premetamorphic tadpoles were treated with 5 nM triiodothyronine to induce metamorphosis, a significant decrease in mdr message and protein was observed after 3 days, a time at which the primary epithelium remained intact. Furthermore, in thyroid-hormone treated primary cultures of brush border epithelial cells, a reduction in mdr message also was observed. These results demonstrate that the Xe-mdr gene is developmentally regulated and suggest a role for thyroid hormone in this process. This is the first report of a naturally occurring substance that can down-regulate mdr gene expression in vivo.
Zucker
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Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
Castillo
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Band Horwitz
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D000818:Animals; D015536:Down-Regulation / Q000187:drug effects; D004848:Epithelium / Q000254:growth & development / Q000378:metabolism / Q000648:ultrastructure; D019450:Genes, MDR / Q000187:drug effects*; D017403:In Situ Hybridization; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000254:growth & development / Q000648:ultrastructure; D007814:Larva / Q000235:genetics / Q000254:growth & development; D008675:Metamorphosis, Biological / Q000187:drug effects / Q000235:genetics; D008854:Microscopy, Electron; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014284:Triiodothyronine / Q000494:pharmacology*; D014982:Xenopus laevis / Q000235:genetics* / Q000254:growth & development*
D012333:RNA, Messenger; D014284:Triiodothyronine