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去势后人、大鼠和豚鼠血浆及前列腺组织中残余C-19类固醇的比较:睾丸外雄激素在男性中的独特重要性。

Comparison of residual C-19 steroids in plasma and prostatic tissue of human, rat and guinea pig after castration: unique importance of extratesticular androgens in men.

作者信息

Bélanger B, Bélanger A, Labrie F, Dupont A, Cusan L, Monfette G

机构信息

MRC Group in Molecular Endocrinology, Laval University Medical Center, Quebec, Canada.

出版信息

J Steroid Biochem. 1989 May;32(5):695-8. doi: 10.1016/0022-4731(89)90514-1.

DOI:10.1016/0022-4731(89)90514-1
PMID:2525654
Abstract

The concentrations of dehydroepiandrosterone (DHEA), its sulfate (DHEAS), androstenedione (A-dione), testosterone (T) and dihydrotestosterone (DHT) have been measured before and after castration in men and two animal models, namely the rat and the guinea pig. In adult men, the pre-castration levels of plasma DHEAS and DHEA were measured at 1839 +/- 320 and 2.4 +/- 0.5 ng/ml, respectively, while in both animal models, the concentrations of these two steroids were below 0.3 ng/ml. Orchiectomy in men reduced plasma T and DHT levels from 2.9 +/- 0.1 and 0.60 +/- 0.10 to 0.42 +/- 0.21 and 0.05 +/- 0.01 ng/ml (P less than 0.01), respectively, while there was no significant effect observed on DHEAS, DHEA and A-dione levels. By contrast, castration in the rat reduced the low levels of circulating DHEA and A-dione below the detection of the radioimmunoassay (RIA) used. In castrated guinea pig, a small quantity of plasma A-dione (0.07 +/- 0.02 ng/ml) was measured while DHEA was undetectable. Moreover, in the rat and guinea pig, plasma T and DHT levels became undetectable. Following administration of the antiandrogen Flutamide for two weeks in the castrated rat and guinea pig, prostate weight was not further reduced, thus indicating that there is no significant androgenic activity left following castration of these two species. In fact, castration in the rat and guinea pig caused a decrease in prostatic levels of DHT from 4.24 +/- 0.351 and 9.42 +/- 1.43 ng/g, respectively, to undetectable levels. In men, on the other hand, the prostatic DHT levels were only inhibited from 5.24 +/- 0.59 to 2.70 +/- 1.50 ng/g, respectively. As expected, when Flutamide was administered to the rat and the guinea pig, the levels of prostatic steroids remained undetectable while, in men, the DHT content in the prostate was further reduced to undetectable values. In summary, the plasma levels of DHEAS, DHEA, delta 4-dione are markedly different between men and both animal models used and furthermore, measurements of prostatic levels of androgens suggest that the high plasma levels of these steroids are likely responsible for the presence of important amounts of DHT in human prostate after castration.

摘要

在男性以及大鼠和豚鼠这两种动物模型中,分别测量了去势前后脱氢表雄酮(DHEA)、其硫酸盐(DHEAS)、雄烯二酮(A - 二酮)、睾酮(T)和双氢睾酮(DHT)的浓度。成年男性去势前血浆DHEAS和DHEA水平分别测得为1839±320和2.4±0.5 ng/ml,而在两种动物模型中,这两种类固醇的浓度均低于0.3 ng/ml。男性睾丸切除术后,血浆T和DHT水平分别从2.9±0.1和0.60±0.10降至0.42±0.21和0.05±0.01 ng/ml(P<0.01),而对DHEAS、DHEA和A - 二酮水平未观察到显著影响。相比之下,大鼠去势使循环中的低水平DHEA和A - 二酮降至所用放射免疫分析(RIA)的检测限以下。去势豚鼠中,测得少量血浆A - 二酮(0.07±0.02 ng/ml),而DHEA未检测到。此外,在大鼠和豚鼠中,血浆T和DHT水平变得无法检测到。在去势大鼠和豚鼠中给予抗雄激素氟他胺两周后,前列腺重量未进一步减轻,这表明这两个物种去势后不存在显著的雄激素活性。事实上,大鼠和豚鼠去势导致前列腺DHT水平分别从4.24±0.351和9.42±1.43 ng/g降至无法检测到的水平。另一方面,在男性中,前列腺DHT水平仅从5.24±0.59分别抑制至2.70±1.50 ng/g。正如预期的那样,当给大鼠和豚鼠施用氟他胺时,前列腺类固醇水平仍无法检测到,而在男性中,前列腺中的DHT含量进一步降至无法检测到的值。总之,男性与所使用的两种动物模型之间,DHEAS、DHEA、δ4 - 二酮的血浆水平存在显著差异,此外,雄激素前列腺水平的测量表明,这些类固醇的高血浆水平可能是人类去势后前列腺中存在大量DHT的原因。

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