Oestrogen agonistic effects of tamoxifen in the uterus of newborn guinea pigs after short and long treatment. Biological and histological studies

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.