Thyroid hormone controls the cell-specific expression of the kidney androgen-regulated protein gene in S3 mouse...

The kidney androgen-regulated protein (KAP) gene is expressed in epithelial cells of proximal convoluted tubules of mouse kidney. Although TSH proved to be necessary for the constitutive expression of the gene in the outer stripe of the outer medulla, androgens are responsible for expression in cortical segments of the proximal tubules. We have used the congenital thyroid hormone (TH)-deficient hyt/hyt mouse to demonstrate that TH, and not TSH, is responsible for the constitutive expression of the gene in the mouse kidney. Although the androgen-dependent cortical response is partially impaired in hypothyroid mice, the expression can be fully restored after the administration of TH or pharmacological doses of testosterone, suggesting some cooperativity between TH and androgens in promoting cortical KAP gene expression. Results in hyt/hyt mice after treatment with retinoic acid, alone or in combination with TH, demonstrated that this regulator does not have any effect on the regulation of the KAP gene in mouse kidney and that induction of the gene by T3 does not require heterodimerization of TR with retinoic acid-related receptors. By using immunocytochemical analysis and specific antibodies against alpha- and beta-TH receptors we have determined the presence of both types of receptors in all segments of the proximal tubules.