Androgen receptors in chemically-induced colon carcinogenesis.

Cytoplasmic extracts (105,000 x g supernatants) prepared from the colon of 1,2-dimethylhydrazine hydrochloride (DMH) treated male BD-IX rats bound 3H-5 alpha-dihydrotestosterone (DHT) with high affinity (Kd = 3 x 10(-9) M) and low capacity (n = 20 fmoles/mg protein). Unoccupied saturable binding sites were not detected in normal intact colon but were observed in colons from gonadectomized rats. DHT receptors were present in both the ascending and descending segments of the colon. The DHT binding components sedimented as 7--8S species on linear sucrose density gradients and were effectively displaced by cyproterone acetate, but not by progesterone. Forty percent of the DMH-induced colon tumors also bound DHT with high affinity and limited capacity. These results suggest that the sex steroids are involved in carcinogen-induced colon tumorigenesis, and the action is mediated by their association with sex steroid specific receptors.