Relationship between induction of mammary tumors and change of testicular functions in male rats following gamma-ray irradiation and/or diethylstilbestrol.

Male Wistar-MS (W/MS), Fisher-344 (F-344) and Sprague-Dawley (SD) rats were divided into four groups including a control group implanted with a cholesterol pellet. Rats in the three experimental groups were treated with gamma-ray irradiation (260 cGyt) alone, diethylstilbestrol (DES) pellet implantation alone or both irradiation and DES, and all rats were observed for detection of mammary tumors for 1 year. Morphologically, well-developed mammary glands were observed in the SD rats at ages corresponding to the time of irradiation. But, the mammary glands in the W/MS and F-344 rats showed a lower degree of differentiation than those in the SD rats. No mammary tumor developed spontaneously in the W/MS and F-344 strains of rats during the experimental period. The rats administered both DES and irradiation showed significantly increased incidence of mammary tumors compared with the control, the incidence being 80.9% in the SD rats, 35.0% in the W/MS rats, and 9.4% in the F-344 rats, respectively. The incidence of tumor in the SD rats treated with irradiation alone and with DES alone was 9.5% and 14.3%, respectively, but no tumor development was observed in the F-344 rats treated with either irradiation alone or DES alone or in the W/MS rats treated with DES alone. The magnitude of the decrease of testicular weight in the SD rats implanted with DES after irradiation (to 70% of the control weight) was slightly less marked than that in either the W/MS (35%) or F-344 (16%) rats. The testicular atrophy showed a correlation with the accessory sex organ weight at the end of the experiment, serum testosterone concentration, and incidence of mammary tumors. Following administration of DES pellets after the irradiation, the activity of delta 5-3 beta- and of 17 beta-hydroxysteroid dehydrogenase in the testes showed the order F-344 < W/MS = SD and F-344 = W/MS < SD, respectively. Compared with the control, the irradiated F-344 rats implanted with DES pellets showed hypertrophied pituitary glands (10.7-fold, P < 0.01) as well as increased serum prolactin concentration (21.4-fold, P < 0.01). Of the three strains treated with both irradiation and DES, the F-344 rats showed the highest concentration of serum prolactin but the lowest incidence of mammary tumors. Our results suggest that W/MS, F-344 and SD male rats have differing susceptibilities for the induction of mammary tumor following irradiation. We discuss the relationship between testicular and pituitary functions and male mammary tumorigenesis.