REFRACTORINESS TO MAMMARY TUMORIGENESIS IN PAROUS RATS - IS IT CAUSEDBY PERSISTENT CHANGES IN THE HORMONAL ENVIRONMENT OR PERMANENT BIOCHEMICAL-ALTERATIONS IN THE MAMMARY EPITHELIA

Administration of a single i.v. injection of 50 mg N-methyl-N-nitrosou rea (MNU)/kg body wt to 50- to 60-day-old virgin rats, 120-day-old vir gin rats, and 120-day-old parous rats (Sprague-Dawley; n = 18-37) resu lted in a high incidence of mammary carcinomas in the virgin animals ( 97.3% in 50- to 60-day-old virgin rats; 75.0% in 120-day-old virgin ra ts), but mammary carcinomas did not develop in the parous rats, The co ncentrations in serum of various mammotropic hormones were measured in identical groups of rats at the time of MNU treatment, Growth hormone (GH) concentration was significantly reduced in parous rats, as compa red with young or age-matched virgin rats, The concentrations of prola ctin, 17 beta-estradiol, progesterone, corticosterone and thyroxine we re not significantly altered in the parous rats compared to the two gr oups of virgin animals, Histological examination of the mammary glands from the three groups of rats showed that the epithelia of the parous animals were in a stage of regression, whereas the mammae of the youn g virgin rats showed the highest degree of lobulo-alveolar development , The levels of estrogen receptor (ER), epidermal growth factor (EGF) receptor (EGF-R) and GH receptor (GHR) in the mammary glands of the an imals were also measured, We found a reduction in the receptor levels for both estrogen and EGF in mammary tissues from parous animals, Rece ptors for GH were present in normal mammary tissues from both virgin a nd parous rats, We hypothesize that the reduction in the circulating c oncentration of GH caused the reduced susceptibility of parous rats to mammary carcinogenesis possibly by decreasing the levels of ER and/or EGF-R in the mammary gland.