当前位置： SCI文献检索 > TOXICOLOGY AND APPLIED PHARMACOLOGY期刊下所有文献 > Comparative activities of 2,3,7,8-tetrachlorodibenzo-p-dioxin and progesterone as antiestrogens in the female rat uterus.

Comparative activities of 2,3,7,8-tetrachlorodibenzo-p-dioxin and progesterone as antiestrogens in the female rat uterus.

Abstract：

:The comparative antiestrogenic effects of progesterone and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on cytosolic and nuclear estrogen (ERc and ERn, respectively) and progesterone (PRc and PRn, respectively) receptor levels were determined in female Long Evans rats. Estradiol treatment typically increases ER and PR levels in target cells or tissues and these proteins have been proposed as markers of estrogen action. 2,3,7,8-TCDD causes a dose-dependent decrease in uterine ERc, ERn, PRc, and PRn levels which persist up to 7 days. Progesterone treatment caused significant decreases in uterine ERc, ERn, and PRn levels; however, after 7 days, the effects of the hormone on receptor levels were diminished. The effects of 2,3,7,8-TCDD and progesterone on hepatic ER and PR levels were comparable to those observed in the uterus. Treatment of the rats with estradiol (5 micrograms/kg), estradiol (5 micrograms/kg) plus progesterone (1 mg/animal), or 2,3,7,8-TCDD (80 micrograms/kg) showed that both progesterone and 2,3,7,8-TCDD significantly antagonized the estradiol-mediated increases in uterine (and hepatic) ERc, ERn, PRc, and PRn levels and for 2,3,7,8-TCDD the decreased receptor levels persisted for up to 7 days. In vitro studies with freshly isolated uterine strips demonstrated that both 2,3,7,8-TCDD and progesterone antagonized the estradiol-mediated increases in ER and PR levels. Previous studies suggest that the antiestrogenic activity of progesterone is due, in part, to the induction of proteins which are involved in decreasing ERn levels in target cells. Moreover in the uterine strip assay procedure, it was previously shown and reproduced in this study that the decrease in uterine ERn by progesterone was inhibited by both protein and RNA synthesis inhibitors over a 4-hr incubation period. In contrast, the 2,3,7,8-TCDD-mediated decrease in uterine ERn was inhibited only by actinomycin D and not by cycloheximide or puromycin. These in vitro studies thus confirm that both progesterone and 2,3,7,8-TCDD exhibit comparable antiestrogenic effects in vivo and in vitro; however, the results suggest that these effects are expressed through different mechanisms.

journal_name

Toxicol Appl Pharmacol

journal_title

Toxicology and applied pharmacology

authors

Romkes M,Safe S

doi

10.1016/0041-008x(88)90177-9

subject

Has Abstract

pub_date

1988-03-15 00:00:00

pages

368-80

issue

eissn

0041-008X

issn

1096-0333

journal_volume

pub_type

杂志文章

在线工具

Comparative activities of 2,3,7,8-tetrachlorodibenzo-p-dioxin and progesterone as antiestrogens in the female rat uterus.