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.