THYROID-HORMONE CONTROLS THE CELL-SPECIFIC EXPRESSION OF THE KIDNEY ANDROGEN-REGULATED PROTEIN GENE IN S3 MOUSE KIDNEY-CELLS

The kidney androgen-regulated protein (KAP) gene is expressed in epith elial cells of proximal convoluted tubules of mouse kidney. Although T SH proved to be necessary for the constitutive expression of the gene in the outer stripe of the outer medulla, androgens are responsible fo r expression in cortical segments of the proximal tubules. We have use d the congenital thyroid hormone (TH)-deficient hyt/hyt mouse to demon strate that TH, and not TSH, is responsible for the constitutive expre ssion of the gene in the mouse kidney. Although the androgen-dependent cortical response is partially impaired in hypothyroid mice, the expr ession can be fully restored after the administration of TH or pharmac ological 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 combinat ion 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 T-3 does not require heterodimerization of TR with reti noic acid-related receptors. By using immunocytochemical analysis and specific antibodies against alpha- and beta-TH receptors we have deter mined the presence of both types of receptors in all segments of the p roximal tubules.