Pozzi P, Bendotti C, Simeoni S, Piccioni F, Guerini V, Marron T U, Martini L, Poletti A
Institute of Endocrinology, Center of Excellence on Neurodegenerative Diseases, University of Milan, Milano, Italy.
J Neuroendocrinol. 2003 Sep;15(9):882-7. doi: 10.1046/j.1365-2826.2003.01074.x.
Spinal cord motoneurones express high levels of androgen receptor. However, in responsive tissue, the effects of testosterone is often mediated by the more potent androgenic derivative 5-alpha-dihydrotestosterone (DHT). This compound is formed in androgen target cells by the enzyme 5-alpha-reductase. Two isoforms of the 5-alpha-reductase, with limited degree of homology, have been cloned, type 1 and type 2. The low affinity-constitutive type 1 isoenzyme is widely distributed in the body; the high affinity-androgen regulated 5-alpha-reductase type 2 is confined to androgen-dependent structures and shows a peculiar pH optimum at acidic values. We have previously shown that high levels of 5-alpha-reductase activity are detectable in rat spinal cord. Here, using reverse transcriptase-polymerase chain reaction, we show that both isoforms are expressed in the whole spinal cord of the rat. The enzymatic pH optimum measured in immortalized spinal cord motoneurones (NSC34) is typical of the type 2 isoenzyme. Using in situ hybridization technique, we found that 5-alpha-reductase type 2 is confined to the motoneuronal cells of the anterior horns of the rat spinal cord, the cells that also are known to express high levels of androgen receptor. Because of the close association of androgen receptor and 5-alpha alpha-reductase type 2, motoneuronal cells should be considered as target cells for androgens.
脊髓运动神经元表达高水平的雄激素受体。然而，在反应性组织中，睾酮的作用通常由更强效的雄激素衍生物5-α-二氢睾酮（DHT）介导。该化合物由5-α-还原酶在雄激素靶细胞中形成。已克隆出5-α-还原酶的两种亚型，同源性有限，即1型和2型。低亲和力组成型1型同工酶在体内广泛分布；高亲和力雄激素调节的5-α-还原酶2型局限于雄激素依赖结构，在酸性值时显示出特殊的最适pH值。我们之前已表明，在大鼠脊髓中可检测到高水平的5-α-还原酶活性。在此，利用逆转录聚合酶链反应，我们表明两种亚型在大鼠整个脊髓中均有表达。在永生化脊髓运动神经元（NSC34）中测得的酶最适pH值是2型同工酶的典型特征。利用原位杂交技术，我们发现5-α-还原酶2型局限于大鼠脊髓前角的运动神经元细胞，这些细胞也已知表达高水平的雄激素受体。由于雄激素受体与5-α-还原酶2型密切相关，运动神经元细胞应被视为雄激素的靶细胞。
