Meseguer A, Catterall J F
Population Council, Rockefeller University, New York, N.Y. 10021.
Rev Esp Fisiol. 1990 Mar;46(1):69-78.
Steady state measurements of kidney androgen-regulated protein (KAP) mRNA suggested that KAP gene expression was unusually sensitive to low hormone-receptor levels. Two of the criteria used to reach this conclusion involved relative insensitivity to treatment with a competitive antiandrogen and a partial androgen response of the gene in Tfm/Y androgen receptor (AR) deficient mice. These data may indicate the ability of the KAP gene to respond to an extremely low level of androgen-AR complex or that the effect of androgens is, at least in part, indirect. Hybridization in situ revealed that KAP mRNA expression was restricted to proximal tubule epithelial cells in the juxtamedullary region of castrated animals rather than throughout the cortex as in intact males. Examination of sections of kidneys from Tfm/Y mice before and after testosterone (T) treatment revealed that only the juxtamedullary tubules expressed KAP mRNA and that T increased the level of KAP mRNA in these cells. Treatment of Tfm/Y animals with other steroids showed that beta-estradiol treatment mimicked the effect of T while dihydrotestosterone (DHT) had no effect. The facts that DHT and T both stimulate cortical expression of KAP mRNA in normal animals but DHT has no effect on the juxtamedullary cells in the Tfm/Y variant may indicate that the action of T is due to an estrogenic metabolite. Castrated, hypophysectomized males exhibited no KAP gene expression, while in the presence of T, expression was observed throughout the cortex as in intact males. These results clearly indicate the involvement of pituitary hormones in KAP gene expression in the juxtamedullary tubules. These studies have shown that the regulation of KAP gene expression in the mouse kidney is much more complex than originally believed. Future studies will further investigate the roles of estrogen and specific pituitary hormones in KAP gene expression.
对肾脏雄激素调节蛋白（KAP）mRNA的稳态测量表明，KAP基因表达对低激素受体水平异常敏感。得出这一结论所使用的两个标准涉及对竞争性抗雄激素治疗相对不敏感，以及该基因在Tfm/Y雄激素受体（AR）缺陷小鼠中的部分雄激素反应。这些数据可能表明KAP基因对极低水平的雄激素-AR复合物有反应的能力，或者雄激素的作用至少部分是间接的。原位杂交显示，KAP mRNA表达仅限于去势动物近髓质区域的近端小管上皮细胞，而不像完整雄性动物那样遍布整个皮质。对Tfm/Y小鼠睾酮（T）治疗前后的肾脏切片检查显示，只有近髓质小管表达KAP mRNA，并且T增加了这些细胞中KAP mRNA的水平。用其他类固醇对Tfm/Y动物进行治疗表明，β-雌二醇治疗模拟了T的作用，而双氢睾酮（DHT）则没有效果。DHT和T在正常动物中均刺激KAP mRNA的皮质表达，但DHT对Tfm/Y变体中的近髓质细胞没有影响，这一事实可能表明T的作用是由于一种雌激素代谢产物。去势、垂体切除的雄性动物未表现出KAP基因表达，而在有T的情况下，如完整雄性动物一样在整个皮质中观察到表达。这些结果清楚地表明垂体激素参与了近髓质小管中KAP基因的表达。这些研究表明，小鼠肾脏中KAP基因表达的调节比最初认为的要复杂得多。未来的研究将进一步探讨雌激素和特定垂体激素在KAP基因表达中的作用。
