Biomaterial Database

Opposing biological actions of antiestrogens in vitro and in vivo: induction of progesterone receptor in the rat and mouse uterus. 1985

C A Campen, and V C Jordan, and J Gorski

The nonsteroidal antiestrogen tamoxifen, 4-hydroxytamoxifen, and Ly117018 inhibited the estradiol-stimulated induction of progesterone receptors in primary cultures of immature rat uterine cells. This effect was found to be completely reversible with increased concentrations of estradiol. These compounds possessed no estrogenic activity. In contrast, ICI 47,699 (the cis geometric isomer of tamoxifen) and ICI 77,949 (tamoxifen without the dimethylaminoethyl side chain) were fully estrogenic, and bisphenol (4-hydroxytamoxifen without the dimethylaminoethyl side chain) possessed mixed estrogenic/antiestrogenic activity. In primary uterine cell cultures derived from mature ovariectomized mice, 4-hydroxytamoxifen was, again, nonestrogenic and inhibited the estradiol-stimulated induction of progesterone receptors. The antiestrogenic activity of 4-hydroxytamoxifen was effective against both steroidal and nonsteroidal estrogens in either rat- or mouse-derived uterine cell cultures. Using the 3-day uterine assay in vivo, 4-hydroxytamoxifen partially stimulated progesterone receptor induction in the immature rat, whereas it fully stimulated the same end point in the mature ovariectomized mouse. These results emphasize the difference between antiestrogen activity in vivo and in vitro, and also indicate that the increased agonist activity of 4-hydroxytamoxifen in the mouse compared to that in the rat in vivo is not reflected in vitro. Therefore, we have extended the model of antiestrogen action previously described in primary pituitary cell cultures to progesterone receptor induction in two murine uterine cell cultures.

UI	MeSH Term	Description	Entries
D008813	Mice, Inbred ICR	An inbred strain of mouse that is used as a general purpose research strain, for therapeutic drug testing, and for the genetic analysis of CARCINOGEN-induced COLON CANCER.	Mice, Inbred ICRC,Mice, ICR,Mouse, ICR,Mouse, Inbred ICR,Mouse, Inbred ICRC,ICR Mice,ICR Mice, Inbred,ICR Mouse,ICR Mouse, Inbred,ICRC Mice, Inbred,ICRC Mouse, Inbred,Inbred ICR Mice,Inbred ICR Mouse,Inbred ICRC Mice,Inbred ICRC Mouse
D011759	Pyrrolidines	Compounds also known as tetrahydropyridines with general molecular formula (CH2)4NH.	Tetrahydropyridine,Tetrahydropyridines
D011980	Receptors, Progesterone	Specific proteins found in or on cells of progesterone target tissues that specifically combine with progesterone. The cytosol progesterone-receptor complex then associates with the nucleic acids to initiate protein synthesis. There are two kinds of progesterone receptors, A and B. Both are induced by estrogen and have short half-lives.	Progesterone Receptors,Progestin Receptor,Progestin Receptors,Receptor, Progesterone,Receptors, Progestin,Progesterone Receptor,Receptor, Progestin
D002478	Cells, Cultured	Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.	Cultured Cells,Cell, Cultured,Cultured Cell
D004958	Estradiol	The 17-beta-isomer of estradiol, an aromatized C18 steroid with hydroxyl group at 3-beta- and 17-beta-position. Estradiol-17-beta is the most potent form of mammalian estrogenic steroids.	17 beta-Estradiol,Estradiol-17 beta,Oestradiol,17 beta-Oestradiol,Aerodiol,Delestrogen,Estrace,Estraderm TTS,Estradiol Anhydrous,Estradiol Hemihydrate,Estradiol Hemihydrate, (17 alpha)-Isomer,Estradiol Monohydrate,Estradiol Valerate,Estradiol Valeriante,Estradiol, (+-)-Isomer,Estradiol, (-)-Isomer,Estradiol, (16 alpha,17 alpha)-Isomer,Estradiol, (16 alpha,17 beta)-Isomer,Estradiol, (17-alpha)-Isomer,Estradiol, (8 alpha,17 beta)-(+-)-Isomer,Estradiol, (8 alpha,17 beta)-Isomer,Estradiol, (9 beta,17 alpha)-Isomer,Estradiol, (9 beta,17 beta)-Isomer,Estradiol, Monosodium Salt,Estradiol, Sodium Salt,Estradiol-17 alpha,Estradiol-17beta,Ovocyclin,Progynon-Depot,Progynova,Vivelle,17 beta Estradiol,17 beta Oestradiol,Estradiol 17 alpha,Estradiol 17 beta,Estradiol 17beta,Progynon Depot
D004965	Estrogen Antagonists	Compounds which inhibit or antagonize the action or biosynthesis of estrogenic compounds.	Estradiol Antagonists,Antagonists, Estradiol,Antagonists, Estrogen
D005260	Female		Females
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D013045	Species Specificity	The restriction of a characteristic behavior, anatomical structure or physical system, such as immune response; metabolic response, or gene or gene variant to the members of one species. It refers to that property which differentiates one species from another but it is also used for phylogenetic levels higher or lower than the species.	Species Specificities,Specificities, Species,Specificity, Species
D013237	Stereoisomerism	The phenomenon whereby compounds whose molecules have the same number and kind of atoms and the same atomic arrangement, but differ in their spatial relationships. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 5th ed)	Molecular Stereochemistry,Stereoisomers,Stereochemistry, Molecular,Stereoisomer