The effect of several sex steroid hormones on the growth rate of three morris hepatoma tumor lines

Abstract

Morris hepatoma 44, whose growth is sensitive to thyroid hormones and prolactin, contains specific receptors for these hormones. In the present experiments, male Buffalo rats bearing Morris hepatoma 7787 were studied to determine the effects of several sex steroid hormones. Castration 1 week postimplantation inhibited tumor growth relative to controls (-53%). Replacement with testosterone propionate (1 mg per day s.c. injection) restored tumor growth to control levels, whereas administration of testosterone (2 mg per day s.c. injection) to castrated controls resulted in significant stimulation. Testosterone administered to control animals at a dose of 1 mg per day stimulated tumor growth (62%), whereas 2 mg per day failed to do so. Progesterone (4-pregnon-3,20-dione) at doses of 125 or 250 micrograms per day (Silastic implants) had no effect on tumor growth, whereas 500 micrograms per day stimulated tumor growth relative to controls. Estrogen (17 beta-estradiol) at doses of 6, 12, or 24 micrograms per day (Silastic implants) did not influence tumor growth. Cytoplasmic testosterone receptors have been demonstrated in tumors (2.2 +/- 0.8 fmoles per mg cytoplasm), although specific cytoplasmic estrogen and progesterone receptors could not be identified in this model. In female rats bearing either Morris hepatoma 44, 7787 or 5123-D, testosterone markedly stimulated tumor growth (226, 328 and 58%, respectively, relative to controls). In conclusion, although Morris hepatoma 7787 appears to be androgen (testosterone) dependent and contains cytoplastic androgen receptors, it lacks specific cytoplasmic receptors for estrogen and progesterone and is not influenced by these hormones except at very high doses of progesterone.

Sex Hormone Dependency of Diethylnitrosamine‐induced Liver Tumors in Mice and Chemoprevention by Leuprorelin

“…When spayed mice were treated with testosterone, serum testosterone level rose and the tumor incidence became 100% in female mice, confirming that testosterone potentiated the growth of liver tumors. 29) Similar decreased incidence of carcinogen-induced hepatomas in orchidectomized male rats and increased incidence of chemically induced liver tumors in ovariectomized female rats were suggested to be mostly mediated by the respective sex hormones via effects on carcinogen metabolism and activation. [30][31][32] Hormonal responsiveness of tumors, however, is also related to the presence of the relevant receptor.…”

Suppressive effect of oestradiol on chemical hepatocarcinogenesis in rats

“…7 In rat studies, testosterone appears to be a growth factor for Morris hepatoma 7787. 8 These findings suggest that androgens may be implicated in the aetiology of HCC, and that oestrogens may have a suppressive role in the development of human liver cancer. However, oral contraceptive agents are reported as hyperplastic agents in liver and are thought to be implicated in the development of hepatic adenoma and focal nodular hyperplasia in both sexes.…”

“…[5][6][7][8] Most studies [42][43][44] involving cytosolic and nuclear androgen receptor levels of HCC samples have suggested increased androgen receptor positivity or androgen receptor levels in HCC as compared with normal liver tissue. These findings are in accordance with our data indicating a significant decrease in serum testosterone levels in noncastrated males after oestradiol administration and a significant increase in hepatic cytosolic androgen receptor levels in females that received castration and testosterone, in association with the development of preneoplastic liver lesions.…”

Suppressive effect of oestradiol on chemical hepatocarcinogenesis in rats

“…Substituted androgens have been associated with the development of HCC in patients with Fanconi’s anaemia,6 and aplastic anaemia 7. In rat studies, testosterone appears to be a growth factor for Morris hepatoma 7787 8. These findings suggest that androgens may be implicated in the aetiology of HCC, and that oestrogens may have a suppressive role in the development of human liver cancer.…”