Morphological changes induced by testosterone in the mammary glands of female Wistar rats

Abstract

Increased levels of androgens in postmenopausal women are considered to be a risk factor for breast cancer. Testosterone, alone or in combination with estrogen, induces epithelial dysplasia and mammary tumors in Noble rats. Since this model of hormone-induced neoplasia has not been reported in other rat strains, we studied the effect of testosterone on the mammary gland morphology of female Wistar rats. Sixty adult, non-castrated, female Wistar rats were implanted in the dorsum midline with a silicone tube containing 50 mg testosterone (testosterone propionate in 30 animals and non-esterified testosterone in the remaining 30 animals) and 20 additional animals were implanted with empty tubes and used as control. Five animals per group were killed 30, 60, 90, 120, 150, and 180 days after implantation, and the mammary glands were dissected, fixed and embedded in paraffin. Histological sections were then stained with hematoxylin and eosin and picrosyrius red for collagen visualization. Morphological and morphometric analysis demonstrated ductal proliferation and acinotubular differentiation with secretory activity in all treated animals, peaking at 90 days of androgen exposure. After 90 days the proliferation of acinar epithelial cells was evident, but there was a progressive reduction of secretory differentiation and an increase in intralobular collagen fibers. There was no morphological evidence of dysplastic changes or other pre-neoplastic lesions. Testosterone treatment applied to adult, non-castrated female Wistar rats induced a mammary gland hyperplasia resembling the lactating differentiation, with progressive reduction in secretory differentiation. Correspondence

Hormonal and genotoxic estrogen‐androgen carcinogenesis in the NBL rat prostate: A role for aromatase

“…There is, however, evidence from studies with female ACI rats that catechol metabolites of E2, including 4OH‐E2, can be genotoxic to mammary tissue 21 . Other rat strains than the NBL rat also respond to combined T plus E2 treatment with the development of prostate cancer as we have shown in Sprague–Dawley rats 33 and mammary lesions in female Wistar rats have been reported after T plus E2 treatment 34 …”

“…21 Other rat strains than the NBL rat also respond to combined T plus E2 treatment with the development of prostate cancer as we have shown in Sprague-Dawley rats 33 and mammary lesions in female Wistar rats have been reported after T plus E2 treatment. 34 The main question, of course, is whether the T plus E2-treated NBL rat model of prostate carcinogenesis is relevant to the human situation. It will be next to impossible to obtain direct evidence relevant to this issue.…”