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Biomedical subjects

V C Jordan

Publications and source records attributed to V C Jordan.

At least 343 records · Page 19Linked to original sources
PubMed1977

Binding of [3H]tamoxifen in rat uterine cytosols: a comparison of swinging bucket and vertical tube rotor sucrose density gradient analysis.

The interaction of the antioestrogen tamoxifen with rat uterine oestrogen receptor has been studied using swinging bucket and vertical tube rotor techniques of sucrose density gradient analysis. Tamoxifen inhibits the binding of [3H]oestradiol to the 8S oestrogen receptor protein whereas using the swinging bucket rotor technique of sucrose density gradient analysis [3H]-tamoxifen appears to bind to an oestradiol specific protein which sediments at 4-5S. In contrast, using rapid sucrose density gradient analysis with a vertical tube rotor [3H]tamoxifen shows oestrogen specific binding in the 8S region. It is suggested that conventional techniques of sucrose density gradient analysis are unsuited for the investigation of the low affinity ligand interactions with oestrogen receptor proteins since rapid dissociation of complexes can result in ligand binding to nonreceptor proteins.

Animals↗
PubMed1977

A monohydroxylated metabolite of tamoxifen with potent antioestrogenic activity.

The oestrogenic and antioestrogenic properties of tamoxifen and its monohydroxylated (monohydroxytamoxifen) and dihydroxylated (dihydroxytamoxifen) metabolites have been investigated in the immature rat. Whether administered orally or subcutaneously, monohydroxytamoxifen was more active than tamoxifen as an antioestrogen. Dihydroxytamoxifen was less active than tamoxifen as an antioestrogen, but this derivative alone was unable to induce a uterotrophic response. Both metabolites of tamoxifen were potent inhibitors of the binding of [3H]oestradiol to oestrogen receptors in vitro. It is possible that the metabolites play a supportive role in the antioestrogenic activity of tamoxifen. The potent activity of monohydroxytamoxifen in vivo and in vitro suggests that this compound could be an important new tool for the subcellular investigation of oestrogenic and antioestrogenic events.

Animals↗
PubMed1977

Steroid and prostaglandin relations during the menstrual cycle.

Estrone, estradiol (E2), progesterone, prostaglandin E (PGE), and prostaglandin F (PGF) were measured simultaneously in uterine and peripheral venous plasma. PGE and PGF were determined in endometrial curettage samples. Prostaglandin levels decreased in the absence of an intact blood supply; therefore, tissue samples were all taken before hysterectomy. The levels of ovarian steroids were found to be higher in uterine venous, compared with peripheral venous plasma. PGF levels were significantly higher (P less than 0.01) in secretory endometrium compared with proliferative endometrium and throughout the cycle PGF levels in the endometrium were linearly related to the log10 concentration of E2 in uterine venous blood (P less than 0.001). PGE levels remained constant throughout the menstrual cycle.

Adult↗
PubMed1976

Considerations into the mechanism of estrogen-stimulated uterine prostaglandin synthesis.

Progesterone priming of the ovariectomized rat, followed by a single injection of estradiol-17beta (10 mug) is followed by an increased uterine synthesis of both PGF and PGE. The administration of an estrogen antagonist (MER-25; 10 mg) concomitantly with estradiol had no effect on uterine prostaglandin synthesis. Similarly, the administration of either Actinomycin D or cycloheximide, antibiotics demonstrated to inhibit mRNA and protein synthesis, respectively, is without effect on estrogen-stimulated uterine prostaglandin synthesis. These results are considered with regard to the classic receptor theory of estrogen action and are a preliminary indication that estrogen-stimulated uterine prostaglandin synthesis may not require those receptor mediated events.

Animals↗
PubMed1976

The effect of reported prostaglandin synthetase inhibitors on estradiol-stimulated uterine prostaglandin biosynthesis in vivo in the ovariectomized rat.

Aspirin, indomethacin and naproxen have been shown to inhibit the release of prostaglandins E and F (PGE and PGF) from the estradiol-stimulated uterus of progesterone-pretreated ovariectomized rats. Under the present experimental conditions indomethacin (1 mg/rat) was found to be a potent inhibitor of PGF and E biosynthesis, but the duration of action was less than 24 hours, after which a rebound above control levles was observed.The compounds were without effect on estradiol-stimulated increases in uterine wet weight. delta'THC did not inhibit estradiol-stimulated PG biosynthesis but produced a significant rise (P less than 0.01) in PGE levels in uterine venous blood. A hypothesis is suggested to explain some of the pharmacological effects of delta'THC.

Animals↗
PubMed1976

Oestrogenic, anti-oestrogenic and fertility effects of some triphenylethanes and triphenylethylenes related to ethamoxytriphetol (MER 25).

Five triphenylethylenes, a triphenylethane and a triphenylethanol, carrying methyl substituents ortho to one or both of the ring oxygen functions, have been examined for oestrogenic, and antioestrogenic activity in mice, and three of the compounds, alpha-[4-(beta-diethylaminoethoxy)-3, 5-xylyl]-alpha-phenyl-beta-4-methoxyphenyl-ethanol (IV), alpha'-[4-(beta-diethylaminoethoxy)-3, 5-xylyl]-4-methoxy-bibenzyl (V) and alpha'-[4-(beta-diethylaminoethoxy)-3, 5-xylyl]-4-methoxy-stilbene (VI), were tested for their effects on fertility in mice. 2 Orthomethylation reduces oestrogenic and/or anti-oestrogenic activity compared with the reported activities of non-methylated analogues. 3 The anti-oestrogenic ethamoxytriphetol (MER 25) reduced fertility in mice whereas its inactive dimethylated analogue (IV) was ineffective. The weakly active anti-oestrogens, V and VI, did not affect fertility in mice.

Animals↗
PubMed1976

Tamoxifen as an anti-tumour agent: effect on oestrogen binding.

Tamoxifen (ICI 46,474) has been shown to possess anti-tumour properties in the dimethylbenz(a)anthracene (DMBA)-induced rat mammary carcinoma model. During tamoxifen therapy the binding of [3H]oestradiol in vivo to uterine (P less than 0-001), vaginal (P less than 0 X 01) and tumour (P less than 0-001) tissues was significantly reduced. Tamoxifen therapy was without effect on the binding of [3H]oestradiol in heart tissue. The determination of specific oestrogen-binding components in vitro was significantly reduced (P less than 0-01) in tumours from tamoxifen-treated rats and tamoxifen inhibited the binding of [3H]oestradiol to 8S oestrogen-binding components, derived from rat uteri and DMBA-induced tumours, in vitro.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1976

Tamoxifen as an anti-tumour agent: role of oestradiol and prolactin.

Four-day cyclic rats fed 7, 12-dimethylbenz(a)anthracene (dmba) (20 mg) at 50 days of age had peak prolactin, oestradiol and uterine wet weights at pro-oestrus. Tamoxifen (50, 200 and 800 mug daily), administered to ovariectomized rats, produced significant (P less than 0 X 05) decreases in oestrogen-stimulated prolactin levels but was unable to reduce prolactin to control values. Tamoxifen (12 X 5, 50 and 200 mug daily) produced decreases in size in DMBA-induced rat mammary carcinomata in intact rats although some tumours did not respond to therapy. The ability of the pituitary to produce prolactin was not impaired. Decreases in uterine wet weights and peripheral oestradiol levels occurred during tamoxifen treatment.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1976

Tamoxifen as an anti-tumour agent: oestrogen binding as a predictive test for tumour response.

Rats with growing 7,12-dimethylbenz(alpha)anthracene (DMBA)-induced rat mammary carcinomata were biopsied and oestrogen-binding capacity was measured using a Sephadex LH-20 chromatography method. Tumours were measured with calipers and animals were treated for 3 weeks with tamoxifen (50 mug/day, S.C.). Tumour response was determined by the size (cm2) before and after therapy. An increase in tumour regression (ten tumours) was seen with increasing oestrogen-binding sites determined by Scatchard analysis (P less than 0.01). Thirty tumours were used to determine oestrogen binding with a single dose of [3H]-oestradiol. The percentage tumour regression was linearly correlated with oestrogen-binding capacity (P less than 0.01), although some tumours with high oestrogen-binding capacities only partially regressed in response to tamoxifen therapy. The time of the oestrous cycle when biopsy occurred was not a critical factor in determining oestrogen binding for prediction of response. Oestrogen binding was reduced during tamoxifen therapy.

Animals↗
PubMed1976

Antiestrogenic and antitumor properties of tamoxifen in laboratory animals.

This paper reviews the antiestrogenic and antitumor properties of tamoxifen (NSC-180973; ICI-46474) in the rat. In classic tests for antiestrogenic activity, tamoxifen inhibits the actions of estradiol in the rat uterus and vagina. At the cellular level, tamoxifen inhibits estrogen binding to cytoplasmic estrogen receptors, but although estrogen-receptor units are translocated to the nucleus DNA synthesis does not occur. It is suggested that tamoxifen competes for estrogen receptors in the cytoplasm and the false messenger units block the nuclear acceptors which are normally activated by estradiol-estrogen receptor complexes thereby provoking DNA synthesis. Tamoxifen inhibits the growth of some 7.12-dimethylbenz(a)anthracene-induced rat mammary tumors whereas others continue to grow. Estrogen-stimulated rises in plasma prolactin are only partially inhibited by tamoxifen although at the tumor level, tamoxifen completely blocks estrogen binding. There is a linear correlation (P less than 0.01) between estrogen-receptor levels in tumor biopsies before therapy and tumor responses to 3 weeks of tamoxifen treatment (50 mug/day) i.e., tumors with low levels of estrogen receptors do not respond to therapy whereas tumors with higher levels of estrogen receptors regress. It is suggested that tamoxifen antagonizes the actions of estrogen at the tumor level by blocking the estrogen-receptor mechanism thereby producing tumor regression. Therefore, estrogen-receptor measurements in tumor biopsies before therapy may be a useful predictive test for the tumor response to tamoxifen treatment.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1975

Prolonged antioestrogenic activity of ICI 46, 474 in the ovariectomized mouse.

Subcutaneous administration of ICI 46,474 (3 mg) to ovariectomized mice was found to produce vaginal refractoriness to subcutaneously administered oestradiol for up to 6 weeks. Tritiated oestradiol-17 beta accumulated in the uterus and vagina of the ovariectomized mouse, with maximum accumulation at 3 to 4 hr. This property of the target tissues was used to investigate the binding of tritiated oestradiol after the administration of 3 mg ICI 46,474 to ovariectomized mice. Radioactivity in the vagina was found to be comparable to control values 6 weeks after ICI 46,474 administration; uterine levels of radioactivity returned to control values by 10 weeks. Administration of ICI 46,474 had an oestrogenic effect upon the mouse uterus whereas the vagina appeared to be initially stimulated and was then unable to respond to or to bind oestradiol.

Animals↗