First Author | Mahendroo MS | Year | 2001 |
Journal | Endocrinology | Volume | 142 |
Issue | 11 | Pages | 4652-62 |
PubMed ID | 11606430 | Mgi Jnum | J:72807 |
Mgi Id | MGI:2153626 | Doi | 10.1210/endo.142.11.8510 |
Citation | Mahendroo MS, et al. (2001) Unexpected virilization in male mice lacking steroid 5alpha-reductase enzymes. Endocrinology 142(11):4652-62 |
abstractText | Mice lacking steroid 5alpha-reductase 1 and 2 were produced by gene targeting and breeding. Male mice without 5alpha-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 5alpha-reductase 2 and increased the weights of the prostate, seminal vesicle, and coagulating gland in animals deficient in both enzymes. An inhibitor of both 5alpha-reductases (GI 208335X) decreased prostate and coagulating gland weights of control mice, but had no effect in those lacking 5alpha-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 5alpha-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 5alpha-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. |