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
M
M
Kodama Research Institute of Preventive Medicine, Tokyo, Japan.
Kodama
T
T
Kodama
M
M
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