ON THE SIGNIFICANCE OF SEX HORMONES IN PRODUCING EXPERIMENTAL PROSTATE TUMOR IN THE RAT

• Published in: Kurume medical journal Vol. 22; no. 3; pp. 113 - 134
• Main Author: HIGUCHI, MASAHITO
• Format: Journal Article
• Language: English
• Published: Kurume University School of Medicine 1975
• ISSN: 0023-5679; 1881-2090
• DOI: 10.2739/kurumemedj.22.113

Experimental production of prostate cancer in the animals may contribute to diagnosis and therapy of human prostate cancer by utulizing as a model of provocation, initiation and pathophysiology of the cancer. It is interesting and important to know in detail the effects of sex hormones on carcinogenic mechanism of prostate cancer which has been supposed to be androgen-dependent. The present author has investigated the influence of sex hormones upon experimental prostate tumor formation, and obtained the following results. 1. In the Donryu rats which have been considered to be vary low in spontaneous tumor formation rate, experiments of tumor formation were performed by direct injection of 1% 20-MC or 4-NQO olive oil solution to the ventral lobe of the prostate and by subcutaneous transplantation of 20-MC or 4-NQO crystal wrapped with the prostate epithelial tissue. In addition, the effects of endocrine milieu on the rate of tumor formation were investigated. 2. The rate of tumor formation was as follows : namely, in the rat group with direct injection of carcinogenic substance to the ventral lobe of the prostate the tumor occurred in 50% by 20-MC and in 51.3% by 4-NQO and in the rats with transplantation of wrapped carcinogenic substances the tumor formation rate was 27.8% by 20-MC and 19.6% by 4-NQO. The results of the cases associated with change in endocrine milieu could be summarized as follows. In the rat group with direct injection of carcinogenic substances, the rats with castration or with estrogen administration after castration showed higher rate in tumor formation than the rats with only carcinogenic substance, and androgen administration caused reduction in tumor formation rate regardless of methods to produce. In the rat group with transplantation of the wrapped carcinogenic substances, although there was no significant difference in tumor formation rate between the rats with only carcinogenic substance and those with androgen, castration or estrogen administration after castration obviously resulted in an increase in tumor formation rate. However, the tumor formation rate was clearly lower in the female rats with subcutaneous transplantation than in the male rats with the same procedure. 3. The tumors formed experimentally were pathohistologically classified as follows. In the rat group with direct injection, adenoma was seen in 15%, squamous cell carcinoma in 37.5%, and sarcoma in 47.5%. In the rat group with subcutaneous transplantation, adenoma was observed in 32%, squamous cell carcinoma in 36%, and sarcoma in 32%. Estrogen administration resulted in an evident increase in weight of the tumors formed. In summary, the present author has failed to provoke experimentally prostate adenocarcinoma which occupies a majority of human prostate cancer. This, special attention was paid to adenoma formed in the rats. Experimentally produced adenoma was originated from the glandular tissue of the prostate. This type of rat prostate adenoma could be subcutaneously transplanted to the other rats of the same strain. It was attempted to clarify the effects of the change in endocrine milieu on the transplanted adenoma, and the following results were obtained. 1) The rate of successful transplantation was 51.25% in the male rats and 40.00% in the female rats. 2) Histological division of the transplanted tumor was done as follows in the male rats : adenoma was seen in 5%, squamous cell carcinoma in 5%, and sarcoma in 5%. Transplanted adenoma tended to alter to malignant one with increasing the time after transplantation. In the female rats, transplanted adenoma changed to adenocarcinoma in 4%, and the cases of adenoma unchaged were 36%. 3) When endocrine milieu was experimentally changed, the results were summarized. In the rats with hexestrol application after castration, the rate of successful transplantation was 60% and the rate to provoke adenocarcinoma was 20%. In the female rats, the rate of successf