Ladle D R, Jacobson N A, Lephart E D
Department of Zoology-Cellular Biology Division, Brigham Young University, Provo, Utah 84602, U.S.A.
Life Sci. 1997;61(20):2017-26. doi: 10.1016/s0024-3205(97)00860-6.
The metabolism of steroid hormones in the medial basal hypothalamus (MBH) is known to play a critical role in neural development, the modulation of neuroendocrine function and regulating sexual behavior. While the important biological functions of the aromatase enzyme are well established, the importance of brain 5alpha-reductase has been revealed and elucidated only in the last few years. The distribution and regulation of brain aromatase and 5alpha-reductase enzyme activities have been investigated for the most part in male rats. Therefore, in the present study, MBH aromatase cytochrome P450 and 5alpha-reductase activities were characterized in pregnant and female rats during postnatal development under various hormonal conditions. MBH aromatase activity was determined in each tissue sample using the 'tritiated water release' assay, whereas, the 5alpha-reductase rates were determined by thin layer chromatography and scintillation counting of the isolated 5alpha-metabolites. Both activities were highest in infantile animals, then declined with increasing postnatal age; whereas, in aged non-cycling or ovariectomized/adrenalectomized (Ovx/Adx) rats high rates of androgen metabolism were seen in MBH tissue. No significant alterations in MBH aromatase were observed when the 5alpha-reductase pathway was blocked in pregnant animals during late gestation with a known 5alpha-reductase inhibitor (Proscar). However, plasma estradiol levels were significantly increased in the Proscar-treated animals. These results indicate that: 1) the decreasing MBH aromatase and 5alpha-reductase profile (in infantile to adult cycling animals) is developmentally regulated, 2) evidently, there is a divergent regulatory mechanism controlling MBH aromatase versus 5alpha-reductase in aged animals where the aromatase activity increased in aged non-cycling and Ovx/Adx rats while 5alpha-reductase rates remained at moderate levels and, 3) apparently, the 5alpha-reductase pathway is not involved in regulating MBH aromatase activity during late pregnancy.
已知内侧基底下丘脑（MBH）中类固醇激素的代谢在神经发育、神经内分泌功能调节及性行为调控中发挥关键作用。虽然芳香化酶的重要生物学功能已得到充分证实，但脑5α-还原酶的重要性仅在过去几年才被揭示和阐明。脑芳香化酶和5α-还原酶活性的分布及调节大多在雄性大鼠中进行了研究。因此，在本研究中，对处于产后发育阶段、处于各种激素条件下的怀孕和雌性大鼠的MBH芳香化酶细胞色素P450及5α-还原酶活性进行了表征。使用“氚水释放”测定法测定每个组织样本中的MBH芳香化酶活性，而5α-还原酶活性则通过薄层色谱法及对分离出的5α-代谢物进行闪烁计数来测定。两种活性在幼年动物中最高，随后随着出生后年龄的增加而下降；然而，在老年非周期性或去卵巢/肾上腺切除（Ovx/Adx）大鼠的MBH组织中，雄激素代谢率较高。当在妊娠后期用一种已知的5α-还原酶抑制剂（保法止）阻断怀孕动物的5α-还原酶途径时，未观察到MBH芳香化酶有明显变化。然而，保法止处理的动物血浆雌二醇水平显著升高。这些结果表明：1）MBH芳香化酶和5α-还原酶活性（从幼年到成年周期性动物）的下降是受发育调控的；2）显然，在老年动物中，控制MBH芳香化酶与5α-还原酶的调节机制不同，老年非周期性和Ovx/Adx大鼠中芳香化酶活性增加，而5α-还原酶活性保持在中等水平；3）显然，5α-还原酶途径在妊娠后期不参与调节MBH芳香化酶活性。
