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C J Dix

Publications and source records attributed to C J Dix.

42 records · Page 3Linked to original sources
PubMed1978

Dose-related effects of non-steroidal antioestrogens nad oestrogens on the measurement of cytoplasmic oestrogen receptors in the rat and mouse uterus.

The dose-related effects of non-steroidal antioestrogens and oestrogens on the measurement of cytoplasmic oestrogen receptors in the rat uterus have been determined. The simultaneous administration of tamoxifen or monohydroxytamoxifen and oestradiol on three consecutive days resulted in dose-dependent decreases in both the wet weight of the uterus and the number of available cytoplasmic oestrogen receptors. The oestrogenic triphenylethylenes ICI 47 699 and ICI 3188 both produced dose-dependent decreases in the number of available cytoplasmic oestrogen receptors. Increasing doses of ICI 47 699 resulted in increasing concentrations of oestrogen receptors within the nucleus. The effects of tamoxifen and oestradiol-17 beta were compared in the ovariectomized mouse; replenishment of uterine oestrogen receptors was less evident in tamoxifen-treated animals than in animals receiving oestradiol, although increases in uterine weight were similar. A single large dose of tamoxifen (50 microgram) produced a prolonged depletion of cytoplasmic oestrogen receptors whilst stimulating rises in uterine weight and DNA and protein content. The results demonstrate that the depletion of the uterine cytoplasmic oestrogen receptor pool is a function of the dose administered for any compound with the ability to translocate oestrogen receptors to the nucleus and as such is not an exclusive characteristic of non-steroidal antioestrogens.

Animals↗
PubMedDate not supplied

Nonsteroidal antiestrogens: their biological effects and potential mechanisms of action.

The uterotropic and antiuterotrapic effects of a variety of structural derivatives of the nonsteroidal antiestrogen tamoxifen have been determined in the rat and the mouse. One derivative, monohydroxytamoxifen, was found to be a potent antiestrogen in the rat, with a high affinity for the estrogen receptor. Various techniques of sucrose density gradient analysis were used to demonstrate that estradiol and tamoxifen bind to the rat uterine cytoplasmic estrogen receptor. Estrogens and antiestrogens provoke the translocation of estrogen receptors to the nucleus and deplete the cytoplasmic estrogen receptor pool for short or long periods depending on the dose administered. Estradiol stimulates endometrial hyperplasia with an increase in total uterine DNA content, whereas tamoxifen stimulates endometrial hypertrophy with only a slight increase in uterine DNA content. It is concluded that the molecular shape of the ligand that binds to the estrogen receptor determines antiestrogenic activity.

Animals↗
PubMedDate not supplied

Pharmacology of tamoxifen in laboratory animals.

This paper reviews the recent laboratory findings about the nonsteroidal antiestrogen, tamoxifen, and its more potent major metabolite, monohydroxytamoxifen. Both compounds stimulate progesterone receptor synthesis in the rat uterus, and there is an inhibition of cell division in the uterine luminal epithelial cells. The effects of tamoxifen in vivo may be a result of the net effects of the parent compound and monohydroxytamoxifen. In rats with dimethylbenzanthracene (DMBA)-induced rat mammary carcinomata, young tumors that are estrogen receptor- and progesterone receptor-rich respond more favorably to tamoxifen that do older estrogen receptor- and progesterone receptor-poor tumors. However, the antitumor effect of tamoxifen in the DMBA-induced rat mammary carcinoma model is probably a result of the blockade of tumor estrogen receptors, a reduction in circulating gonadotropins, lower circulating estrogen levels, and lower circulating prolactin levels. The 30-days treatment of rats with tamoxifen 30 days after DMBA resulted in a dose-related decrease in the appearance and numbers of mammary tumors; however, only continuous therapy maintained animals in a tumor-free state. Monohydroxytamoxifen was a less-potent antitumor agent, probably because it is cleared from the rat more rapidly than tamoxifen. The present laboratory findings support the clinical use of tamoxifen as a treatment of endometrial carcinoma and the resultant metastases and as an adjuvant therapy after surgery for breast cancer.

9,10-Dimethyl-1,2-benzanthracene↗