Interaction between N-methyl-N'-nitro-N-nitrosoguanidine and 2 steroid hormones in the glandular stomach of mouse. II. Retardation of local dihydrotestosterone turnover by use of a rice-rich diet and the carcinogen.
We investigated the question of whether or not N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), a gastrocarcinogen with a structural resemblance to the antiandrogenic gastrosuppressant cimetidine, had a similar antiandrogenic activity in the glandular stomach of mouse. Possible influence of a rice-rich diet on the interaction of androgen with the same tissue was also studied in relation to its gastrosuppressive effect. The results obtained were as follows: 1) excess MNNG non-competitively inhibited the specific binding of 3H-dihydrotestosterone (DHT) with the cytoplasmic receptor of the glandular stomach of mouse; 2) the MNNG intake slowed down local 3H-DHT turnover in the glandular stomach of mouse; 3) evidence was presented to indicate that MNNG action was antiandrogenic in nature; 4) a rice-rich diet, exerting a weight-decreasing influence on the glandular stomach, also slowed down the 3H-DHT turnover in the same tissue. It was indicated that both MNNG and a rice-rich diet produced a state of androgen depression in the glandular stomach of mouse by slowing down the turnover of local androgen and/or competing with local androgen for its receptor in the target tissue. The significance of the results was discussed in relation to the etiology of gastric cancer.
Kodama Research Institute of Preventive Medicine, Tokyo, Japan.
M
M
Kodama
T
T
Kodama
M
M
Kodama
D000818:Animals; D013196:Dihydrotestosterone / Q000378:metabolism*; D004347:Drug Interactions; D005753:Gastric Mucosa / Q000378:metabolism*; D008297:Male; D008769:Methylnitronitrosoguanidine / Q000378:metabolism / Q000494:pharmacology*; D051379:Mice; D008815:Mice, Inbred Strains; D012275:Oryza; D011944:Receptors, Androgen / Q000378:metabolism
D011944:Receptors, Androgen; D013196:Dihydrotestosterone; D008769:Methylnitronitrosoguanidine