Diethylstilboestrol (DES) has been observed to stimulate the growth of oestrogen-sensitive tumours in premenopausal women and yet DES therapy has been reported to increase survival significantly in 30% of postmenopausal women with breast cancer (Kelley, 1971).It has been suggested that in premenopausal women, DES may be metabolically converted by the ovary to a closed-ring system which resembles a natural oestrogen and therefore possesses true oestrogenic activity (Hoge, Shaw, Bottomley & Hartsuck, 1975). However, in postmenopausal women, because the ovarian tissue is atrophied, DES would not be converted into a natural oestrogen and could act as an antioestrogen (Hoge et al. 1975). The purpose of the present study was to examine the influence of endocrine ablation on the oestrogenic activity of DES in young mice. It was anticipated that if DES were converted to a natural oestrogen in vivo, the most likely places for the metabolic conversion to occur would be the ovary or the adrenal gland, due to their ability to synthesize steroids and because of the clinical observations mentioned above.Oestrogenic activity was evaluated by a slight modification of the method of Rubin, Dorfman, Black & Dorfman (1951) using immature (10-14 g) Swiss-Webster mice. Diethylstilboestrol was administered s.c. in 0-1 ml sesame oil; control animals received sesame oil alone. All animals were treated daily for 3 consecutive days with a total dose of 0-4 µg DES. On day 4 the mice were weighed and then killed, and the uteri dissected out and weighed to the nearest 0-1 mg. Because of the fluid and electrolytic changes in the adrenalecto¬ mized mice and the resultant potential for significant changes in body weight, both the total uterine weight and the ratio total uterine weight (mg) : body weight (g)(U: B), which reduces variation due to differences in animal size to a minimum, were used to assess the uterotrophic activity of DES. The mice underwent endocrine ablation or sham operation the day before treatment with DES was begun. The adrenalectomized and adrenalectomized-ovariectomized animals were given 0-9% saline solution instead of drinking water. Analysis of variance was used to make statistical comparisons between multiple group means and Student's r-test was used to compare individual groups.The results presented in Fig. 1 indicate that neither the ovary nor the adrenal gland are necessary for the uterotrophic activity of DES ; the total uterine weight and the U : ratios were significantly increased in the DES-treated sham-operated and endocrine-ablated groups (P< 0-001). Furthermore, there was no significant difference in the response to DES between the four experimental groups. The results of the present study indicate that the oestrogenic activity of DES in vivo is independent of the presence of a functional ovary or adrenal gland in the immature mouse. However, it is possible that DES may be converted to a closed-ring metabolite in tissues other than the ovary or adrenal gland, such as the liver and fat cells, which are known t...

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