Comparative effects of progesterone, norgestrel, norethisterone and tamoxifen on the abnormal uterus of the anovulatory rat.

Progesterone therapy results in partial reversibility of histological abnormalities of the rat uterus exposed to constant oestrogen stimulation and is associated with a decrease in nuclear oestrogen receptor content, which may underlie the tissue response to hormone treatment [White, Moore, Elder & Lim (1982) Biochem. J. 202, 535-41]. The synthetic progestins norgestrel and norethisterone used in this study were as effective as progesterone in decreasing the content of nuclear oestrogen receptor. However, only norgestrel had an ameliorative effect on epithelial hyperplasia and metaplasia. The non-steroidal anti-oestrogen tamoxifen caused a significant decrease in both nuclear and cytosol oestrogen receptor content without any change in luminal epithelial hyperplasia and metaplasia. Each progestin caused an increase, whereas tamoxifen caused a decrease, in the proportion of nuclear oestrogen receptors that were unoccupied. Each compound caused a decrease in the content of cytosol progesterone receptor. The effectiveness of compounds used as oestrogen antagonists is discussed with reference to their mode of action.