19-Hydroxylation of androgens in the rat brain.
19-Hydroxylation of androgens in the rat brain.
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大鼠大脑中雄激素的 19-羟基化。
DOI：
10.1073/pnas.82.9.2728
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发表时间：
1985
影响因子：
11.1
通讯作者：
Fishman,J
中科院分区：
文献类型：
--
作者：
Hahn,EF;Miyairi,S;Fishman,J
中枢神经系统雄激素的芳构化与大脑的性别分化有关，因此决定了性行为的性质和对促性腺激素分泌的控制。在人类胎盘中确定的芳构化过程是通过C-19位点连续两次羟基化进行的，其产物随后几乎完全通过C-2位点第三次羟基化转化为雌激素。我们现在报道，在大鼠大脑中，雄激素的19-羟基化大大超过芳构化，19-羟基和19-氧雄激素产物的积累量是雌激素的5倍。这种关系表明，大脑中的芳香化序列缺乏末端羟化酶，并且该过程与其他组织中的过程不同。19-羟基和19-氧睾酮在中枢神经系统中的功能尚不清楚，但与雄性激素的还原或芳香化代谢物不同，这些物质不能从循环中传递，它们在大脑中的存在完全依赖于原位形成，这使它们成为神经元功能调节剂的逻辑候选物。
Aromatization of androgens in the central nervous system is linked with sexual differentiation of the brain and, thus, determines the nature of sexual behavior and the control of gonadotropin secretion. The process of aromatization, as determined in the human placenta, proceeds through two successive hydroxylations at C-19, the products of which are then virtually completely converted via a third hydroxylation at C-2 to estrogens. We now report that in the rat brain, 19-hydroxylation of androgens greatly exceeds aromatization and the 19-hydroxy- and 19-oxoandrogen products accumulate in quantities 5 times greater than the estrogens. This relationship implies that the aromatization sequence in the brain is deficient in the terminal hydroxylase, and the process is distinct from that in other tissues. The function of 19-hydroxy- and 19-oxotestosterone in the central nervous system is unknown but, unlike the reduced or aromatized metabolites of the male hormone, these substances cannot be delivered from the circulation and their presence in the brain is totally dependent on in situ formation, making them logical candidates for modulators of neuronal functions.