Unexpected virilization in male mice lacking steroid 5α-reductase enzymes
Unexpected virilization in male mice lacking steroid 5α-reductase enzymes
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DOI：
10.1210/en.142.11.4652
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发表时间：
2001-11-01
期刊：
影响因子：
4.8
通讯作者：
Russell, DW
中科院分区：
文献类型：
--
作者：
Mahendroo, MS;Cala, KM;Russell, DW
通过基因靶向和育种制备了缺乏类固醇5 α -还原酶1和2的小鼠。没有5 α -还原酶2或没有这两种酶的雄性小鼠具有完全形成的内外生殖器和生育能力，但前列腺和精囊比对照组小。T在突变小鼠的生殖组织中积累到很高的水平。DHT增加了5 α -还原酶2缺乏小鼠的精囊和凝固腺的重量，增加了两种酶缺乏动物的前列腺、精囊和凝固腺的重量。5 α -还原酶的抑制剂（GI 208335X）降低了对照组小鼠的前列腺和凝固腺重量，但对缺乏5 α -还原酶1和2的小鼠没有影响。在所有基因型的动物中，阉割都减少了这些组织的大小。雄激素依赖性基因表达在缺乏一种或多种5 α -还原酶的小鼠精囊中降低，并通过给予T或DHT恢复。缺少这两种酶的雌性小鼠表现出与缺乏5 α -还原酶1的动物相似的分娩和繁殖力缺陷。我们得出结论，睾酮是小鼠雄性泌尿生殖道分化所需的唯一雄激素，DHT的合成主要作为信号放大机制。
Mice lacking steroid 5 alpha -reductase 1 and 2 were produced by gene targeting and breeding. Male mice without 5 alpha -reductase 2 or without both enzymes had fully formed internal and external genitalia and were fertile, but had smaller prostates and seminal vesicles than controls. T accumulated to high levels in the reproductive tissues of the mutant mice. DHT administration increased seminal vesicle and coagulating gland weights in mice deficient in 5 alpha -reductase 2 and increased the weights of the prostate, seminal vesicle, and coagulating gland in animals deficient in both enzymes. An inhibitor of both 5 alpha -reductases (GI 208335X) decreased prostate and coagulating gland weights of control mice, but had no effect in those lacking 5 alpha -reductase 1 and 2. Castration reduced the sizes of these tissues in animals of all genotypes. Androgen-dependent gene expression was decreased in the seminal vesicles of mice lacking one or more 5 alpha -reductases and was restored by administration of T or DHT. Female mice missing both enzymes exhibited parturition and fecundity defects similar to those of animals without 5 alpha -reductase 1. We conclude that T is the only androgen required for differentiation of the male urogenital tract in mice and that the synthesis of DHT serves largely as a signal amplification mechanism.