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雄烯二酮诱导食蟹猴(猕猴)前列腺中雌激素相关的增生性变化及其被芳香化酶抑制剂1-甲基-雄甾-1,4-二烯-3,17-二酮拮抗的作用

Induction of estrogen-related hyperplastic changes in the prostate of the cynomolgus monkey (Macaca fascicularis) by androstenedione and its antagonization by the aromatase inhibitor 1-methyl-androsta-1,4-diene-3,17-dione.

作者信息

Habenicht U F, Schwarz K, Neumann F, el Etreby M F

机构信息

Research Laboratories of Schering AG, Berlin (West), Federal Republic of Germany.

出版信息

Prostate. 1987;11(4):313-26. doi: 10.1002/pros.2990110404.

DOI:10.1002/pros.2990110404
PMID:2446299
Abstract

The cynomolgus monkey was selected as an experimental model to investigate the role of estrogens in the pathogenesis of benign prostatic hyperplasia (BPH) because its prostate seems to be more like the human prostate than that of other primate species. The treatment of intact, adult animals with the aromatizable substrate androstenedione for 3 months resulted in no significant changes in prostate weight, but in microscopically clearly detectable estrogen-related hyperplastic changes, particularly in a marked smooth muscle activation. These effects were antagonized by simultaneous, subcutaneous treatment with the aromatase inhibitor 1-methyl-androsta-1,4-diene-3,17-dione (1-Methyl-ADD) and only partially reversed by oral treatment. The serum estradiol (E2) concentration, which was not significantly elevated after treatment with androstenedione in comparison to the control, was drastically decreased after subcutaneous treatment with 1-Methyl-ADD and moderately decreased after oral treatment. In conclusion, these results as well as the great anatomical and histological similarities between the prostate of the cynomolgus monkey and that of man indicate that it might be a suitable and interesting model for future BPH studies.

摘要

食蟹猴被选为实验模型,以研究雌激素在良性前列腺增生(BPH)发病机制中的作用,因为与其他灵长类动物相比,其前列腺似乎更类似于人类前列腺。用可芳香化的底物雄烯二酮对成年未阉割动物进行3个月的治疗,前列腺重量无显著变化,但在显微镜下可明显检测到雌激素相关的增生性变化,尤其是平滑肌明显激活。这些作用可被同时皮下注射芳香化酶抑制剂1-甲基-雄甾-1,4-二烯-3,17-二酮(1-Methyl-ADD)所拮抗,口服治疗只能部分逆转。与对照组相比,用雄烯二酮治疗后血清雌二醇(E2)浓度无显著升高,皮下注射1-Methyl-ADD后血清E2浓度急剧下降,口服治疗后血清E2浓度中度下降。总之,这些结果以及食蟹猴前列腺与人前列腺之间巨大的解剖学和组织学相似性表明,它可能是未来BPH研究的一个合适且有趣的模型。

相似文献

1
Induction of estrogen-related hyperplastic changes in the prostate of the cynomolgus monkey (Macaca fascicularis) by androstenedione and its antagonization by the aromatase inhibitor 1-methyl-androsta-1,4-diene-3,17-dione.雄烯二酮诱导食蟹猴(猕猴)前列腺中雌激素相关的增生性变化及其被芳香化酶抑制剂1-甲基-雄甾-1,4-二烯-3,17-二酮拮抗的作用
Prostate. 1987;11(4):313-26. doi: 10.1002/pros.2990110404.
2
Induction of metachromasia in experimentally induced hyperplastic/hypertrophic changes in the prostate of the cynomolgus monkey (Macaca fascicularis).食蟹猴(猕猴属)前列腺实验性诱导增生/肥大性改变中异染性的诱导。
J Urol. 1989 Dec;142(6):1624-6. doi: 10.1016/s0022-5347(17)39181-4.
3
Synergic inhibitory effects of the aromatase inhibitor 1-methyl-androsta-1, 4-diene-3, 17-dione and the antiandrogen cyproterone acetate on androstenedione-induced hyperplastic effects in the prostates of castrated dogs.芳香化酶抑制剂1-甲基雄甾-1,4-二烯-3,17-二酮与抗雄激素醋酸环丙孕酮对去势犬前列腺中雄烯二酮诱导的增生效应的协同抑制作用。
Prostate. 1987;11(2):133-43. doi: 10.1002/pros.2990110205.
4
Selective inhibition of androstenedione-induced prostate growth in intact beagle dogs by a combined treatment with the antiandrogen cyproterone acetate and the aromatase inhibitor 1-methyl-androsta-1,4-diene-3,17-dione (1-methyl-ADD).通过抗雄激素醋酸环丙孕酮和芳香酶抑制剂1-甲基-雄甾-1,4-二烯-3,17-二酮(1-甲基-ADD)联合治疗,选择性抑制成年比格犬中雄烯二酮诱导的前列腺生长。
Prostate. 1989;14(4):309-22. doi: 10.1002/pros.2990140404.
5
Development of a model for the induction of estrogen-related prostatic hyperplasia in the dog and its response to the aromatase inhibitor 4-hydroxy-4-androstene-3,17-dione: preliminary results.犬雌激素相关性前列腺增生诱导模型的建立及其对芳香化酶抑制剂4-羟基-4-雄烯-3,17-二酮的反应:初步结果
Prostate. 1986;8(2):181-94. doi: 10.1002/pros.2990080208.
6
Rationale for using aromatase inhibitors to manage benign prostatic hyperplasia. Experimental studies.使用芳香化酶抑制剂治疗良性前列腺增生的理论依据。实验研究。
J Androl. 1991 Nov-Dec;12(6):395-402.
7
Effects of estrogen deprivation on human benign prostatic hyperplasia.雌激素缺乏对人良性前列腺增生的影响。
J Steroid Biochem Mol Biol. 1993 Mar;44(4-6):573-6. doi: 10.1016/0960-0760(93)90261-t.
8
Effects of long-term administration of androgens and estrogen on rhesus monkey prostate: possible induction of benign prostatic hyperplasia.长期给予雄激素和雌激素对恒河猴前列腺的影响:可能诱发良性前列腺增生。
J Androl. 2000 Nov-Dec;21(6):833-41.
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Atamestane: an aromatase inhibitor for the treatment of benign prostatic hyperplasia. A short review.阿那曲唑:一种用于治疗良性前列腺增生的芳香化酶抑制剂。简要综述。
J Steroid Biochem Mol Biol. 1993 Mar;44(4-6):565-72. doi: 10.1016/0960-0760(93)90260-4.
10
The function and the role of aromatase inhibitors in the treatment of BPH.
Prog Clin Biol Res. 1994;386:209-30.

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