Biological effects and ultrastructural alterations of cis-tamoxifen, N-desmethyltamoxifen and 4-hydroxytamoxifen in the uterus and vagina of newborn guinea pigs

in European Journal of Endocrinology
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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.

 

     European Society of Endocrinology

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