Parous rats regain high susceptibility to chemically induced mammary cancer after treatment with various mammotropic hormones

Parity in humans and rats provides significant protection against mammary t umor development. This study was carried out to investigate whether treatme nt of parous rats with mammotropic hormones would affect methylnitrosourea (MNU)-induced mammary carcinogenesis. Parous rats were treated with 17 beta -estradiol (E2), progesterone (P4) and thyroxine (T4) alone or in combinat ion. E2 (20 mug/60 days) and P4 (20 mg/60 days) were administered by silast ic tubing and T4 in the drinking water (3 mug T4/ml). Hormonal treatments c ommenced 7 days before MNU injection and continued for 33 weeks, Animals we re palpated weekly for tumor detection. The effects of the hormonal treatme nts on the circulating concentrations of E2, P4, growth hormone (GH), prola ctin (PRL), T4 and insulin-like growth factor-I (IGF-I) after 7 days of tre atment, the time of MNU injection, was assessed. Animals treated with E2 ha d significantly elevated circulation concentrations of GH, PRL and P4, and serum levels of E2 were more consistent in this group than in the other ani mal groups. pi treatment caused elevation in P4 concentration in serum but did not affect the circulating levels of other hormones. The proliferation of the mammary gland at the time of MNU injection was elevated in animal gr oups treated with E2 either alone or with P4 and T4 and in animals treated with P4 alone, but the mammary gland was most differentiated in untreated p arous rats and least in animals treated with E2 either alone or with P4 and T4, Mammary tumor incidence was 10% in parous rats that did not receive an y hormonal treatment. Treatments with E2 or P4 alone significantly increase d the susceptibility of parous animals to 67 and 50.0%, respectively; a tum or incidence similar to that of untreated AMV rats (64%). Parous rats treat ed with E2 plus PI had tumor incidence higher than 90%, T4 administered did not affect mammary carcinogenesis.