Stephenson G, Hammet M, Hadaway G, Funder J W
Am J Physiol. 1984 Oct;247(4 Pt 2):F665-71. doi: 10.1152/ajprenal.1984.247.4.F665.
We examined the ontogeny of cytosol mineralocorticoid receptors in renal inner medulla-papilla (IM-PAP) and outer medulla-cortex (OM-CX) and of a biological response to administered corticosteroids (urinary K+/Na+ ratio). Rats at early (7-9 days), intermediate (13-15 days), and late (23-30 days) stages of maturation were used. Young rats were found to be essentially insensitive to aldosterone, in contrast to rats aged 13-15 days and older. Scatchard analysis of IM-PAP and OM-CX cytosol showed equivalent high-affinity aldosterone binding sites at all ages. The affinity of these sites was constant (Kd, 4 degrees C approximately 0.5 nM) and their concentration varied only slightly over maturation. In a series of in vivo nuclear transfer studies, the hyposensitivity to aldosterone in young rats did not seem to be due to a difference in the nuclear binding of aldosterone-receptor complexes. The resistance of the immature (7-9 days) rat kidney to aldosterone thus appears to be a postreceptor phenomenon. The maturational events allowing expression of mineralocorticoid-inducible genes in the kidney remain to be determined.
我们研究了肾内髓-乳头(IM-PAP)和外髓-皮质(OM-CX)中胞质盐皮质激素受体的个体发生,以及对给予的皮质类固醇的生物学反应(尿钾/钠比值)。使用了处于成熟早期(7-9天)、中期(13-15天)和晚期(23-30天)的大鼠。与13-15天及以上的大鼠相比,幼鼠对醛固酮基本不敏感。对IM-PAP和OM-CX胞质进行Scatchard分析显示,在所有年龄段都有相当数量的高亲和力醛固酮结合位点。这些位点的亲和力是恒定的(4℃时Kd约为0.5 nM),其浓度在成熟过程中仅略有变化。在一系列体内核转移研究中,幼鼠对醛固酮的低敏感性似乎并非由于醛固酮-受体复合物核结合的差异。因此,未成熟(7-9天)大鼠肾脏对醛固酮的抵抗似乎是一种受体后现象。肾脏中允许盐皮质激素诱导基因表达的成熟事件仍有待确定。