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一种新型5α-还原酶抑制剂对犬前列腺大小、组织学特征及雄激素浓度的影响

Effect of a new 5 alpha-reductase inhibitor on size, histologic characteristics, and androgen concentrations of the canine prostate.

作者信息

Brooks J R, Berman D, Glitzer M S, Gordon L R, Primka R L, Reynolds G F, Rasmusson G H

出版信息

Prostate. 1982;3(1):35-44. doi: 10.1002/pros.2990030107.

DOI:10.1002/pros.2990030107
PMID:7079196
Abstract

Mature male beagles were used in studies designed to determine the effect of the steroidal 5 alpha-reductase inhibitor 17 beta-N,N-diethylcarbamoyl-4-aza-4-methyl-5 alpha-androstan-3-one (4-MA) on size, histology, and androgen concentration of the prostate. Subcutaneous administration of 3 or 15 mg/kg/day for 43 days caused a sharp decline in prostate volume. flattening of prostatic epithelial cells, vacuolization of the cytoplasm and pycnosis of the nuclei. Whereas serum testosterone levels remained normal in dogs injected with 3 mg/kg/day, they were lower in those that received 15 mg/kg/day. Concentration of both testosterone and 5 alpha-dihydrotestosterone were reduced in the prostates of dogs that had received either 3 or 15 mg/kg/day of 4-MA. The 15 mg/kg/day level also appeared to adversely affect spermatogenesis. In a 43-day study, 4-MA given orally once each day at levels of 0.1, 0.3, or 1 mg/kg failed to cause a significant decrease in prostate volume. However, daily divided oral doses totaling 1 or 3 mg/kg were given in a 42-day test and both treatment levels produced significant reductions in prostate size.

摘要

成年雄性比格犬被用于旨在确定甾体5α-还原酶抑制剂17β-N,N-二乙基氨基甲酰基-4-氮杂-4-甲基-5α-雄甾烷-3-酮(4-MA)对前列腺大小、组织学和雄激素浓度影响的研究中。皮下注射3或15毫克/千克/天,持续43天,导致前列腺体积急剧下降,前列腺上皮细胞扁平,细胞质空泡化,细胞核固缩。注射3毫克/千克/天的犬血清睾酮水平保持正常,而接受15毫克/千克/天的犬血清睾酮水平较低。接受3或15毫克/千克/天4-MA的犬前列腺中睾酮和5α-二氢睾酮的浓度均降低。15毫克/千克/天的剂量水平似乎也对精子发生产生不利影响。在一项为期43天的研究中,每天口服0.1、0.3或1毫克/千克的4-MA未能使前列腺体积显著减小。然而,在一项为期42天的试验中,每天分次口服总量为1或3毫克/千克的4-MA,两种治疗水平均使前列腺大小显著减小。

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1
Effect of a new 5 alpha-reductase inhibitor on size, histologic characteristics, and androgen concentrations of the canine prostate.一种新型5α-还原酶抑制剂对犬前列腺大小、组织学特征及雄激素浓度的影响
Prostate. 1982;3(1):35-44. doi: 10.1002/pros.2990030107.
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引用本文的文献

1
5α-Reductase Isozymes in the Prostate.前列腺中的5α-还原酶同工酶
J Med Sci. 2005;25(1):1-12.
2
Role of 5 alpha-reductase inhibitors in the management of prostate cancer.5α-还原酶抑制剂在前列腺癌治疗中的作用。
Clin Interv Aging. 2006;1(4):425-31. doi: 10.2147/ciia.2006.1.4.425.
3
5alpha-reductase: history and clinical importance.5α-还原酶:历史与临床重要性
Rev Urol. 2004;6 Suppl 9(Suppl 9):S11-21.
4
Molecular Basis of Steroid Action in the Prostate.前列腺中类固醇作用的分子基础。
Cellscience. 2005 Apr 28;1(4):27-55. doi: 10.1901/jaba.2005.1-27.
5
Pharmacokinetics and biochemical efficacy after single and multiple oral administration of N-(2-methyl-2-propyl)-3-oxo-4-aza-5 alpha-androst-1-ene-17 beta-carboxamide, a new type of specific competitive inhibitor of testosterone 5 alpha-reductase, in volunteers.新型睾酮5α-还原酶特异性竞争性抑制剂N-(2-甲基-2-丙基)-3-氧代-4-氮杂-5α-雄甾-1-烯-17β-甲酰胺在志愿者单次及多次口服后的药代动力学及生化效应
Eur J Drug Metab Pharmacokinet. 1991 Jan-Mar;16(1):15-21. doi: 10.1007/BF03189869.
6
Feed-forward control of prostate growth: dihydrotestosterone induces expression of its own biosynthetic enzyme, steroid 5 alpha-reductase.
Proc Natl Acad Sci U S A. 1991 Sep 15;88(18):8044-7. doi: 10.1073/pnas.88.18.8044.