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The effect of hormone therapy on the growth of human colonic adenocarcinoma xenografts in nude mice was evaluated. Primary xeno-transplantation for ten different human colorectal adenocarcinomas into nude mice yielded a tumour take of 50%. One of these host tumours was found to contain androgen receptors (8 fmol/mg cytosol protein; Kd 0.73 x 10(-9) M), which were maintained in the xenograft at the third and ninth passages, but not expressed at the tenth and twelfth passages. The host tumour and its xenograft did not express either oestrogen or progesterone receptors. Administration of dihydrotestosterone led to inhibition of xenograft growth at the ninth passage compared with untreated controls (P less than 0.05), but had no effect on xenograft growth at the tenth and twelfth passages when androgen receptors were absent. Stilboestrol and progesterone failed to influence xenograft growth. In conclusion, dihydrotestosterone administration led to inhibition of xenograft growth only in the presence of androgen receptor, suggesting that some colorectal cancers might be considered steroid-hormone-sensitive tumours.

To evaluate the potential effect of androgens on the development and growth of human colorectal adenomas, the prevalence and concentration of cytosolic androgen receptors (AR) were analysed in 26 adenomas and 19 samples of normal colonic mucosa by a hybrid ligand receptor-binding assay. AR were detected in 7 of the adenomas (26.9%), and in 6 of the normal mucosa samples (31.6%). In the adenomas, AR levels demonstrated were low, ranging from 6 to 31 fmol/mg cytosol protein, and dissociation constants (Kds) ranged from 0.17-2.7 X 10(-9) M. Of 13 adenomas excised from men, 6 (46%) had positive receptor activity, whereas only 1 of 13 (7.7%) from women was positive (P = 0.03, Fisher's exact test). There was no correlation between AR titre and patient age, or between adenoma size and histological type or degree of dysplasia. In normal mucosa, AR levels ranged from 7 to 33 fmol/mg and Kds ranges from 0.24-3.1 X 10(-9) M. There was no significant difference between either AR prevalence or levels in the adenomas and normal mucosa. The sex difference was exclusive to the adenoma. Endogenous androgen may play a role in adenoma development early in the promotional process.