Investigation of the male predominance of bladder cancer

膀胱癌男性多发的调查

• 批准号: 62570718
• 负责人: AKAZA Hideyuki
• 金额: $ 1.28万
• 依托单位: University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1987
• 资助国家: 日本
• 起止时间: 1987 至 1988
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-62570718/
• 关键词: Bladder cancer; Carcinogenesis; N-butyl-N-(4-hydroxybutyl)nitrosamine; LH・RH analogue; Hormone dependency; 性差; LH・RHanalogue; N-butyl-N(4-hydroxybutyl)nitrasamne; LH-RH analogue; ホルモン依存性

To analyze the participation of male hormone in the genesis of urinary bladder carcinoma. We administered gonadotropin-releasing hormone analogue (LH・RH analogue) to the experimental model of male rats where carcinoma is induced by N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN),and further examined the relation between the change of male hormone kinetics and the genesis ratio.Experiment 1: the changes of male rat pituitary-testicular axis induced by a LH・RH analogue were examined. Serum LH, FSH and testosterone levels showed their peaks one day after the LH・RH analogue depot (1 mg/body weight, monthly) injection and decreased afterwards. testo-sterone became castration level one week after the LH・RH analogue injection. BBN did not influence pituitary-testicular axis and action of the LH・RH analogue.Experiment 2: We divided 143 male Wistar rats of 9 weeks into 5 groups. Group 1: 0.05% BBN had been administered for 8 weeks. Group 2: 0.05% BBN and LH・RH analogue for 8 weeks. Group 3: 0.05% BBN for 8 weeks and then LH・RH analogue for 16 weeks. Group 4: 0.05% BBN for 8 weeks and at the same time LH・RH analogue for the overall process. Group 5: 0.05% BBN for 8 weeks after carrying out orchidectomy. Cystectomy was conducted on all of the rats 24 weeks after the experiment had started so as to examine histologically.Diminution of testosterone inhibited rat bladder carcinogenesis induced by BBN. The way of castration, surgical castration or medical castration by LH・RH analogue depot, might act in a different way to inhibit the bladder carcinogenesis. The above phenomenon may indicate the regulatory system in the hypothalamus-pituitary-testicular axis on the bladder carcinogenesis. The inhibition was most significant when LH・RH analogue was administered in the promotion phase of bladder carcinogenesis.Further studies are required to make clear the augmented inhibition of LH・RH analogue on bladder carcinogenesis.

目的：探讨男性激素在膀胱癌发生中的作用。我们在n-丁基- n-（4-羟基丁基）亚硝胺（BBN）诱导癌变的雄性大鼠实验模型上给予促性腺激素释放激素类似物（LH·RH类似物），进一步观察雄性激素动力学变化与发生比的关系。实验1：观察LH·RH类似物对雄性大鼠垂体-睾丸轴的影响。血清LH、FSH和睾酮水平在LH·RH类似物仓库（1 mg/体重，每月）注射后1天达到峰值，随后下降。注射LH·RH类似物1周后睾酮达到去势水平。BBN不影响垂体-睾丸轴和LH·RH类似物的作用。实验二：将143只9周龄雄性Wistar大鼠分为5组。第1组：0.05% BBN给药8周。第2组：0.05% BBN和LH·RH类似物，给药8周。第3组：0.05% BBN治疗8周，然后用LH·RH类似物治疗16周。第4组：0.05% BBN，持续8周，同时在整个过程中使用LH·RH类似物。第5组：0.05% BBN，术后8周。实验开始24周后，所有大鼠均行膀胱切除术，进行组织学检查。睾酮水平降低可抑制BBN诱导的大鼠膀胱癌。通过LH·RH类似物库进行手术阉割或药物阉割，可能以不同的方式抑制膀胱癌的发生。上述现象可能提示下丘脑-垂体-睾丸轴对膀胱癌发生的调控系统。在膀胱癌发生促进期给予LH·RH类似物时，抑制作用最为显著。需要进一步的研究来明确LH·RH类似物对膀胱癌的增强抑制作用。

项目成果

Akaza,H.;Matsuki,K.;Aso,Y.: Cancer.

Akaza,H.；Matsuki,K.；Aso,Y.：癌症。

Akaza, H.; Matsuki, K.; Aso, Y.: "Influences of LH・RH analogue on the rat bladder carcinogeneses" Cancer.

Akaza，H.；Matsuki，K.；Aso，Y.：“LH·RH 类似物对大鼠膀胱致癌的影响”。

赤座英之,松木克之,亀山周二,阿曽佳郎: 日泌尿会誌.

Hideyuki Akaza、Katsuyuki Matsuki、Shuji Kameyama、Yoshiro Aso：日本泌尿外科学会杂志。

赤座英之、松木克之、亀山周二、阿曽佳郎: 日泌尿会誌. 80. (1989)

Hideyuki Akaza、Katsuyuki Matsuki、Shuji Kameyama、Yoshiro Aso：日本泌尿外科杂志 80。（1989）。

Akaza, H.; Matsuki, K.; Kameyama, S.; Aso, Y.: "Influences of LH・RH analogue to the regulation of hypothalamus - pituitary - testicular axis and bladder carcinogenesis" Jap. J. Urol.80. (1989)

Akaza，H.；Kameyama，S.；Kameyama，Y.：“LH·RH 类似物对下丘脑 - 垂体 - 睾丸轴和膀胱癌发生的影响”J. Urol.80。 ）