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Neoplastic Responses and Correlated Plasma Prolactin Levels in Diethylstilbestrol-treated ACI and Sprague-Dawley Rats¹

Medical Department, Brookhaven National Laboratory,³ Upton, New York 11973

Pellets containing 5 mg diethylstilbestrol (DES) and 15 mg cholesterol were implanted s.c. in 84-day-old female Sprague-Dawley (S-D) and ACI rats. [G-³H]DES (32.9 nCi/mg of DES) was incorporated into each pellet. Animals were decapitated, blood was collected at 0, 2, 10, 28, 56, 130, and 214 days after implantation, and the amount of [G-³H]DES remaining in each pellet was determined. Plasma prolactin levels were determined by radioimmunoassay.

DES was released from the implanted pellets exponentially, and the release was not significantly different in S-D rats than in ACI rats. No mammary tumors developed in any treated or untreated S-D rats. In contrast, 90% of the DES-treated ACI rats had developed two or more mammary adenocarcinomas by 130 days, and by 214 days 90% had four or more mammary adenocarcinomas.

A significant increase in the weight of the pituitary was noted in DES-treated ACI rats by 28 days. By Day 130, the pituitaries of the treated ACI rats were 2 to 7 times as heavy as were controls, and plasma prolactin levels were 10 to 40 times higher than in controls. In contrast, the pituitaries of treated S-D rats did not significantly increase in weight, and plasma prolactin levels were only 3 to 5 times higher than controls. As early as Day 10, the uteri of treated S-D rats were significantly heavier than those of control rats and contained large amounts of fluid. This effect was not seen in ACI rats. Although the release of DES from the implanted pellet was essentially the same in ACI and S-D rats, three distinctive strain differences in response to DES were noted: mammary adenocarcinomas were found only in treated ACI rats; pituitary prolactin-cell adenomas and associated elevated plasma prolactins levels were seen only in treated ACI rats; and pyometritis was induced only in treated S-D rats. Mammary adenocarcinomas and prolactin-cell adenoma responses in the treated ACI rats appear to be correlated with the increasing levels of plasma prolactin. This study demonstrates that the prolonged estrogen treatment of ACI and S-D female rats produces distinctly different mammary and pituitary neoplastic responses. This disparity in neoplastic responses appears to be reflected in the difference of degree to which the hypophysial prolactin cells are stimulated to grow and secrete hormone.

¹ Research performed under Contract Y01-CP-30213, with the Biological Models Segment of the Carcinogenesis Program of the National Cancer Institute.

² To whom requests for reprints should be addressed.

³ Operated by Associated Universities, Inc., under contract to the United States Department of Energy, Contract EY-76-C-02-0016.

Received 8/10/78. Accepted 11/22/78.

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