Unusual androgen sensitivity of the androgen-independent Dunning R-3327-G rat prostatic adenocarcinoma: androgen effect on tumor cell loss.

Shessel et al. (Invest. Urol., 17: 529-533, 1980) have reported previously that the serially transplantable Dunning R-3327-G rat prostatic, adenocarcinoma grows faster in intact versus castrated male rats. The present study has demonstrated that this is because the G tumor is composed of androgen-independent but -sensitive prostatic cancer cells. The inclusion that G tumor cells are androgen independent is based upon the observations that these cells are capable of growing following inoculation into castrated male rats and that castration of intact male rats bearing established G tumors induces neither regression of tumor volume nor cessation of the continuous growth of the tumor. The G tumor cells, while being androgen independent, are, however, highly sensitive to androgen for their maximal rate of tumor growth. This androgen sensitivity is demonstrated by the fact that the G tumor cells can be reversibly shifted to a faster or slower growth rate simply by manipulation of the host androgen status. The androgen sensitivity of G tumor growth rate is unusual in that it is not due to androgenic stimulation of cell division but to androgen-induced inhibition of G tumor cell loss (i.e., the rate of G tumor cell loss is reduced by over 50% when androgen is present). The androgen sensitivity of G tumor cell loss is also unusual in that, due to the low level of 5 alpha-reductase activity of the G tumor, the predominant intracellular androgen responsible for this inhibition in untreated intact hosts appears to be testosterone and not dihydrotestosterone (DHT). In castrated rats, however, exogenous treatment with DHT is equally as effective as exogenous testosterone in inhibiting G tumor cell loss. These results suggest that G tumor cells are sensitive to either testosterone or DHT but that in untreated intact hosts little DHT is formed by the tumor cells.