[Effects of female sex steroid hormones on human endometrial adenocarcinoma transplanted into nude mice]

In order to clarify the minute reactions of endometrial adenocarcinoma to sex steroid hormones, especially Progesterone (P), two kinds of in vivo models with differing sex steroid hormone receptor content were transplanted into nude mice. Subsequently, Estrogen (E2) and P were administered alone or together. Sequential histopathological changes, tumor growth curve and volume doubling time were investigated as compared to the castrated control group. Growth rate was increased by E2 administration compared to controls for the model positive for the E2 receptor (ER) and negative for the P receptor (PR), with PR production confirmed in 1 of 3 mice. P produced a slight inhibition of growth, and the inhibitory effect of P was additive with E2. The histological findings consisted of dense solid masses of cells in the tumor in mice treated with E2. The cells decreased in number and in some foci, the tubular glands were cystic in P-treated mice. The number of tumor cells in mice treated with E2 and P was less than in mice given P alone because of a secretive function seen in the appearance of PAS positive granules in the glandular epithelium and degenerative change such as swelling. With the tumor negative for both ER and PR, on the other hand, there was little difference in tumor cell growth between the treated and control groups, and no inhibitory effect was observed after administration of P or coadministration of E2 and P. Histologically, findings with increased nuclear division of tumor cells suggestive of tumor cell growth were obtained after administration of E2 alone and coadministration of E2 and P. E2 exhibited cell growth promoting action in endometrial adenocarcinoma, whether or not ER was present, and P appeared to inhibit tumor cell growth in the presence of ER even when PR was absent. In short, it was suggested that P acted by some mechanism independent of PR. After coadministration of E2 and P, tumor cells were affected in a direction toward functional differentiation in the ER positive tumor. The inhibitory effect of P was obviously additive with E2 in this tumor, while it was suggested that in ER negative tumor, E2 alone promotes tumor cell growth.