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5α-还原酶 1 调节吗啡给药后脊髓中的睾酮。

5α-reductase 1 regulates spinal cord testosterone after morphine administration.

机构信息

Infectious Diseases Department, School of Medicine, Kashan University of Medical Sciences, Kashan, Iran.

出版信息

Neurol Sci. 2013 Jan;34(1):19-23. doi: 10.1007/s10072-012-0936-x. Epub 2012 Jan 19.

DOI:10.1007/s10072-012-0936-x
PMID:22258359
Abstract

The enzyme 5alpha-reductase 1 (5α-R(1)) that converts testosterone (T) to dihydrotestosterone (DHT) is present in many mammalian tissues including the spinal cord. It is established that morphine administration decreases spinal cord T levels, but the mechanism is still undetermined. Here, we investigated the link between T and the enzyme 5α-R(1) in the spinal cord after morphine administration. For spinal cord steroid extraction, all the animals were killed 30 min, 2 h (acute) and 14 days (chronic) after first drug injection by decapitation. The whole spinal cord was removed and kept frozen at -20°C until T and DHT extraction. The effects of acute and chronic morphine administration on 5α-R(1) expression in the adult male rat spinal cord were evaluated using RT-PCR. Spinal cord T and DHT levels were measured using radioimmunoassay before and after the morphine exposure. Morphine significantly reduced the T concentration after acute and chronic exposure in the spinal cord. In contrast, the 5α-R(1) expression and of course DHT levels increased the following chronic morphine administration. One important reason for the decreasing effect of morphine exposure on the spinal cord T level is due to an increase in the 5α-R(1) levels. We suggest that morphine plays a regulatory role in metabolism of neurosteroids, especially T in the spinal cord via 5α-R(1).

摘要

5α-还原酶 1(5α-R(1))可将睾丸酮(T)转化为二氢睾丸酮(DHT),存在于包括脊髓在内的许多哺乳动物组织中。现已证实,吗啡给药会降低脊髓 T 水平,但具体机制尚不清楚。在这里,我们研究了吗啡给药后脊髓中 T 和酶 5α-R(1)之间的联系。为了进行脊髓类固醇提取,所有动物在首次注射药物后 30 分钟、2 小时(急性)和 14 天(慢性)时通过断头处死,以杀死所有动物。取出整个脊髓,在-20°C 下冷冻直至提取 T 和 DHT。使用 RT-PCR 评估急性和慢性吗啡给药对成年雄性大鼠脊髓中 5α-R(1)表达的影响。在吗啡暴露前后使用放射免疫法测量脊髓 T 和 DHT 水平。吗啡显著降低了急性和慢性暴露后脊髓中的 T 浓度。相比之下,5α-R(1)的表达(当然还有 DHT 水平)在慢性吗啡给药后增加。吗啡暴露对脊髓 T 水平的降低作用的一个重要原因是 5α-R(1)水平的增加。我们认为,吗啡通过 5α-R(1)在脊髓中的神经甾体代谢中发挥调节作用,尤其是 T。

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本文引用的文献

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Med Hypotheses. 2011 Feb;76(2):225-9. doi: 10.1016/j.mehy.2010.10.002. Epub 2010 Nov 3.
2
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Med Hypotheses. 2011 Jan;76(1):11-3. doi: 10.1016/j.mehy.2010.08.018. Epub 2010 Sep 18.
3
Finasteride, a 5alpha-reductase inhibitor, potentiates antinociceptive effects of morphine, prevents the development of morphine tolerance and attenuates abstinence behavior in the rat.
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5
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