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5α-双氢睾酮从血清进入脑脊液及去势恒河猴中促黄体生成素的负反馈

The passage of 5 alpha-dihydrotestosterone from serum into cerebrospinal fluid and LH negative feedback in castrated rhesus monkeys.

作者信息

Abbott D H, Batty K A, Dubey A K, Herbert J, Shiers H M

出版信息

J Endocrinol. 1985 Mar;104(3):325-30. doi: 10.1677/joe.0.1040325.

Abstract

Seven castrated monkeys were given either 50 or 100 micrograms 5 alpha-dihydrotestosterone (DHT) propionate/kg per day. There was no correlation between serum and cerebrospinal fluid (CSF) levels of DHT, which remained very low in the CSF (0.3-0.6% of blood levels) despite the presence of high, supraphysiological amounts in the circulation. There was also no relation between unbound DHT in the blood and the CSF, in which all DHT is unbound. These results differ from previous work on testosterone, the metabolic precursor of DHT. 5 alpha-Dihydrotestosterone propionate at the higher dose maintained suppressed levels of serum LH; LH in two out of four monkeys treated at the lower dose increased to levels observed in castrated, untreated rhesus monkeys. There was no predictable relationship between the amount of DHT in the CSF and levels of LH in the blood: by contrast, DHT in the blood was correlated with serum levels of LH. Levels of LH rose in monkeys in which total blood DHT fell below about 68 nmol/l and, even more obviously, if unbound DHT decreased to less than about 2 nmol/l. Differences between the distribution of testosterone and DHT between blood and CSF cannot be explained by serum binding, lipid solubility or clearance from the brain, and suggest that there may be some mechanism for excluding DHT from the CSF. Though DHT reaches the CSF from the blood in small amounts, levels there do not relate predictably to those in the vascular compartment. It seems unlikely, therefore, that levels of intracerebral DHT are controlled by changes in those of the blood.

摘要

给七只去势猴子每天每千克体重注射50或100微克丙酸5α-双氢睾酮(DHT)。DHT的血清水平与脑脊液(CSF)水平之间没有相关性,尽管循环中存在高剂量、超生理量的DHT,但脑脊液中的DHT水平仍然很低(仅为血中水平的0.3 - 0.6%)。血液中游离DHT与脑脊液中的游离DHT之间也没有关系,脑脊液中的所有DHT都是游离的。这些结果与之前关于DHT的代谢前体睾酮的研究不同。较高剂量的丙酸5α-双氢睾酮使血清促黄体生成素(LH)水平维持在较低水平;四只接受较低剂量治疗的猴子中有两只的LH水平升高到了未治疗的去势恒河猴所观察到的水平。脑脊液中DHT的量与血液中LH的水平之间没有可预测的关系:相反,血液中的DHT与血清LH水平相关。当全血DHT降至约68 nmol/l以下时,猴子的LH水平升高,而当游离DHT降至约2 nmol/l以下时,LH水平升高更为明显。睾酮和DHT在血液和脑脊液之间分布的差异无法用血清结合、脂溶性或从脑中的清除率来解释,这表明可能存在某种机制将DHT排除在脑脊液之外。尽管DHT少量从血液进入脑脊液,但其在脑脊液中的水平与血管腔室中的水平并无可预测的关系。因此,脑内DHT水平似乎不太可能受血液中DHT水平变化的控制。

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