Effects of progesterone administration on N-nitrosomethylurea-induced rat mammary carcinogenesis

Abstract

N-Nitrosomethylurea (NMU), 4 mg/100 g body wt, was given to female Sprague-Dawley rats by i.v. injection on 2 occasions, 4 weeks apart. One group of 20 animals also received 5 mg of progesterone s.c. on the morning before, of and after each NMU dose (acute progesterone treatment). A second group of 21 rats was given progesterone 2.5 mg twice a day throughout the experiment commencing 7 days before the first dose of NMU (chronic progesterone treatment). The third group of 20 animals comprised the NMU-exposed controls. The latent period for mammary tumor development was reduced and the number of tumors per rat was increased by the acute progesterone treatment. The final mammary tumor incidence for the chronic progesterone treatment group (62%) was lower than that of the controls (85%) and the acute progesterone-treated rats (80%), and tumor multiplicity was less. Estrogen receptor levels were significantly higher in tumors from the chronic progesterone group than in those from the acute progesterone-treated animals (P < 0.01), and progesterone receptor levels were lower in comparison to either of the other 2 groups. Serum progesterone concentrations were subnormal in the NMU-exposed controls but the estrogens were unaffected. The acute progesterone-treated rats also had reduced serum progesterone levels when compared with normal animals, although they were significantly higher than those of the NMU-exposed controls (P < 0.01). Extremely high serum progesterone levels in rats treated chronically with progesterone were accompanied by reduced estrogen concentrations. Serum prolactin levels were elevated in the NMU-exposed controls and chronic progesterone-treated groups compared with non-NMU-exposed normal rats, while growth hormone concentrations were reduced by progesterone administration. All 3 NMU-exposed groups had elevated serum TSH levels.