N-butyl-N-(4-hydroxybutyl) nitrosamine 投与雄性ラットにおけるLH-RHアナログの下垂体

Abstract

As a first step of investigating male predominance of bladder cancer incidence, we have studied relationships between rat bladder carcinogenesis, induced by BBN, and changes of pituitary-testicular axis, induced by a LH-RH analogue. The rats were divided into the following five groups. The first group (Age matched control group) was given normal drinking water for 30 weeks. The 2nd group (BBN group) was given a drinking water containing 0.05% BBN for 6 weeks. The 3rd group (LH-RH group) was given subcutaneous injections of a LH-RH analogue depot every four weeks. The 4th group (LH-RH + BBN group) was given subcutaneous injections of the LH-RH analogue depot every four weeks and a drinking water containing 0.05% BBN for 6 weeks. The 5th group (castration group) was castrated and given normal drinking water. The results were summarized as follows. 1) Serum LH, FSH and testosterone levels reached their peaks one day after the LH-RH analogue injection and decreased afterwards. Testosterone marked a castration level one week after the LH-RH analogue injection. 2) There was no significant difference between the BBN and non BBN groups in serum LH, FSH and testosterone levels. Thus, BBN did not influence the pituitary-testicular axis and the action of the LH-RH analogues. 3) Incidence of cancer was higher in the group of BBN + LH-RH than in the group of BBN 8 weeks after the start of the experiment. Then, the incidence was reversed between 20 weeks and 26 weeks; finally it became almost the same at 30 weeks. This phenomenon may be explained by the experimented schedule we applied; that is, BBN and LH-RH analogue were administered simultaneously. 4) Thus, changes of the pituitary-testicular axis induced by the LH-RH analogue seemed to have influence on bladder carcinogen.