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  • Author: F. Lecerf x
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F. Lecerf, B.-L. Nguyen and J. R. Pasqualini

Abstract. The biological and morphological effects of cis-tamoxifen, N-desmethyltamoxifen and 4-hydroxytamoxifen, administered sc alone (100 μg/animal) or combined with estradiol (20 μg/animal) were studied in the uterus and vagina of the guinea pig. After 2 days treatment the values of the uterine wet weights (mg ± sd of 6–10 animals in each study) were as follows: non-treated animals (control): 142 ± 15; animals treated with cis-tamoxifen: 119 ± 4; N-desmethyltamoxifen: 280 ± 20; 4-hydroxytamoxifen: 268 ± 25. The values after long treatment were: 177 ± 30; 490 ± 65; 394 ± 36 and 581 ± 60, respectively. After short treatment the weights of the vaginas were: control: 99 ± 20; cis-Tamoxifen: 67 ± 2; N-desmethyltamoxifen: 153 ± 25; 4-hydroxytamoxifen: 166 ± 7; and after the long treatment: 155 ± 40; 660 ± 41; 467 ± 38 and 502 ±61, respectively. N-desmethyltamoxifen and 4-hydroxytamoxifen increased the progesterone receptors in the uterus after short treatment (P < 0.01) but not after 12 days treatment. On the other hand, there was no effect on progesterone receptor in the vagina after the short treatment but a very stimulatory effect after the long treatment. The morphological alterations after 12-days treatment indicate that the three tamoxifen derivatives in the two tissues studied provoke intense alterations in different organelles. In conclusion, it is suggested that the tamoxifen derivatives can act as real agonists in the uterus and vagina of the newborn guinea pig, and they do not block the effect provoked by estradiol.

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J. R. Pasqualini, B.-L. Nguyen, C. Mayrand and F. Lecerf

Abstract. Tamoxifen (TAM) alone or combined with oestradiol (E2) or progesterone (P) was administered to newborn guinea pigs (2 days old) for a short (2 days) or a long (12 days) treatment period. TAM alone provoked a great stimulatory effect on uterine growth and DNA content and the effect was particularly intense after the long treatment. These actions were markedly enhanced when TAM was administered together with E2. Following short treatment, the values of the uterine wet weights (mg ± sd) were as follows: control animals, 142 ± 15; animals treated with TAM, 298 ± 53; E2, 335 ± 15; (TAM + E2), 362 ± 16. The values after the long treatment were 177 ± 30, 555 ± 93, 709 ± 117 and 1263 ± 222, respectively.

Histological studies showed that TAM provoked morphological changes in both the endometrium and the myometrium. The effects were particularly great on the height of the luminal epithelial cells and on the uterine glands. After 2 days of treatment with E2, TAM and P, the thickness of the luminal epithelium, which was 13.5 μm ± 1.5 in the control animals, increased as follows: TAM, 19 μm ± 1.7; E2, 20.3 μm ± 3.3; (TAM + E2), 30.5 μm ± 5; P, 12 μm ± 0.9 and (P + TAM), 19.7 μm ± 1.2. The values after the 12 day treatment were: controls, 20.8 μm ± 1.8; TAM, 27.4 μm ±2.1; E2, 32 ± 3; (TAM + E2), 43 μm ± 5; P, 17.8 μm ± 1.2 and (P + TAM), 23.6 μm ± 1.5. After the short treatment TAM doubled the number of specific progesterone binding sites. It is concluded that TAM acts as a real oestrogen agonist in the uterus of newborn guinea pigs.