Solé E, Calvo R, Obregón M J, Meseguer A
Unitat de Recerca Biomédica, Hospital Universitari Materno-Infantil Vall d'Hebrón, Barcelona, Spain.
Endocrinology. 1994 Nov;135(5):2120-9. doi: 10.1210/endo.135.5.7956935.
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.
肾雄激素调节蛋白（KAP）基因在小鼠肾脏近曲小管的上皮细胞中表达。尽管已证明促甲状腺激素（TSH）对于该基因在外髓质外层条带中的组成性表达是必需的，但雄激素负责该基因在近端小管皮质段中的表达。我们利用先天性甲状腺激素（TH）缺乏的hyt/hyt小鼠来证明，是TH而非TSH负责该基因在小鼠肾脏中的组成性表达。虽然甲状腺功能减退小鼠中雄激素依赖性皮质反应部分受损，但在给予TH或药理剂量的睾酮后，该基因的表达可完全恢复，这表明TH和雄激素在促进皮质KAP基因表达方面存在一定协同作用。用视黄酸单独或与TH联合处理hyt/hyt小鼠后的结果表明，这种调节剂对小鼠肾脏中KAP基因的调控没有任何影响，并且T3对该基因的诱导不需要甲状腺激素受体（TR）与视黄酸相关受体进行异源二聚化。通过免疫细胞化学分析以及针对α和β-TH受体的特异性抗体，我们确定了近端小管所有节段中这两种受体的存在。
