Pattern of Reproductive Aging in Female Rats Can Affect Mammary Tumor Incidence
Reproductive senescence in female rats is due primarily to a developing neuroendocrine failure. Aging Sprague-Dawley (SD) animals demonstrate episodes of persistent vaginal estrus (PVE), while aging Fischer 344 (F-344) rats have episodes of pseudopregnancy. In the present studies, the ratio of serum estrogen to progesterone rose during PVE episodes in mature SD rats. The ratio was also higher than in F-344 rats at the same ages. In addition, SD rats demonstrated a much higher incidence of spontaneous mammary tumors (MT) than did F-344 rats. Among SD female rats fed 400 ppm atrazine, a broad- spectrum herbicide, for 2 years, there was an earlier appearance of PVE episodes, higher estrogen-progesterone ratios, and an earlier appearance of MT, compared to age-matched SD controls. Final tumor incidence, at 24 months, was not increased over control incidence. Indices of reproductive aging were unaffected in F-344 rats fed 400 ppm atrazine, and MT incidence remained low through 24 months. F-344 rats can develop a high rate of MT in response to chemical carcinogens, but did not do so in response to atrazine feeding. Results suggest that the spontaneous MT rate of aging female rats is influenced by exposure to the animals’ own reproductive steroids during middle age, and that the pattern of aging and alteration of the endocrine milieu can correspondingly affect the timing of MT development in senescence.
KeywordsEstrogen Progesterone Estradiol Prolactin Atrazine
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