Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.10.1 (ERK)
 95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In order to clarify the relationship between estradiol binding in the brain and its behavior actions, the effects of 3 antiestrogens (MER-25, CI-628, and nafoxidine) on in vivo tritiated estradiol uptake and retention in cell nuclear fractions or regions of the brain and pituitary were investigated. The ability of antiestrogens to block estradiol-induced female sexual behavior was also studied. Antiestroge were injected 2 hours prior to injection of tritiated estradiol and animals killed 2 hours later. Radioactivity in whole homogenates and isolated cell nuclei of cerebral cortex, hypothalamus, preoptic area-suptum, and pituitary was reduced by CI-628. Nafoxidine reduced uptake in cell nuclei of the hypothalamus, preoptic area-septum, and pituitary. MER-25 only inhibited uptake in the pituitary. CI-628 and nafoxidine totally inhibited lordosis while MER-25 was ineffective when injected 2 hours prior to testing. However, when MER-25 was injected 12 hours prior to testing it inhibited retention of tritiated estradiol in brain and pituitary cell nuclei and lordosis response. When antiestrogens were injected prior to estradiol injection all had greater inhibition of nuclear estradiol retention at 12 hours after the estradiol injection than at 2 hours. When CI-628 was injected 2 hours following injection of tritiated estradiol, most of the radioactivity present in the hypothalamic preoptic area nuclei at 12 hours after the estradiol injection was displaced. Thus antiestrogens can prevent or reverse the nuclear concentration of estradiol in the brain. Female sexual behavior seems to be induced by the presence of estradiol in the cell nucleus.
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PMID:Binding of [3-H]estradiol by brain cell nuclei and female rat sexual behavior: inhibition by antiestrogens. 85 18

The relative binding affinities (RBA) of various compounds for the triphenylethylene antiestrogen binding sites (TABS) were examined. The ability of tamoxifen to inhibit the binding of [3H]tamoxifen to salt extracted (0.4 M KCl) TABS from rat liver nuclei was used as a standard by which other compounds were compared (tamoxifen RBA, 100; Kd approximately 1 nM). Nafoxidine was the most effective triphenylethylene compound used (RBA 333; Kd approximately 0.3 nM) whereas the RBA of zuclomiphene and enclomiphene was not different from tamoxifen. MER-29 was the weakest inhibitor of the triphenylethylene derivatives (RBA 10; Kd approximately 10 nM). Trifluoperazine, chlorpromazine and the anti-calmodulin drugs W-13 and W-12 had RBA's of 25, 1, 1 and 0.1 respectively. The binding affinities of cholesterol and 7-ketocholesterol were significant (Kd approximately 22 nM) while the steroid hormones, estradiol, testosterone, progesterone and corticosterone displayed not observable affinity. Various compounds obtained from Merrill Dow Pharmaceuticals and the Eli Lilly Company which contained alklaminoethoxy side chains linked to aromatic ring structures had RBA's ranging from 1-0.3. We conclude, as other investigators have also concluded, that the similar binding affinities of various triphenylethylene antiestrogens for TABS and their divergent activities as antiestrogens makes it unlikely that TABS are directly involved in estrogen antagonism. The moderate but significant affinity of TABS for trifluoperazine and other drugs thought to be involved in calmodulin regulation indicates that TABS may be a linked in some way to calmodulin function. The binding of cholesterol and 7-ketocholesterol is also significant and may indicate that TABS are involved in cholesterol metabolism.
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PMID:Triphenylethylene antiestrogen binding sites (TABS) specificity. 358 57

A series of experiments examined the effects of two progestins, progesterone and R 5020, and two nonsteroidal antiestrogens, nafoxidine and MER-25, on body weight and composition in female rats. Both progesterone and R 5020 increased food intake, body weight, and carcass adiposity in ovariectomized (OVX) rats treated with estradiol benzoate (EB), but neither progestin had any effect on these measures in OVX rats not treated with EB. R 5020 was substantially more effective than progesterone on all end points. Nafoxidine and MER-25 mimicked the actions of estradiol and decreased adipose tissue lipoprotein lipase (LPL) activity by 75-80%. For adipose tissue LPL activity, both nafoxidine and MER-25 were full estrogen agonists and without antiestrogenic activity. Nafoxidine also mimicked the effects of EB by reducing food intake, body weight, and carcass adiposity in OVX rats. In contrast, nafoxidine antagonized the induction of cytoplasmic progestin ([3H]R 5020) binding sites by EB in parametrial adipose tissue of OVX rats. In nafoxidine-treated OVX rats, concurrent progesterone administration had no effect on adipose tissue LPL activity, but progesterone did increase food intake, body weight, and carcass fat content. Some physiological mechanisms by which gonadal steroids may act to influence eating and adiposity are discussed.
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PMID:Food intake, body weight, and adiposity in female rats: actions and interactions of progestins and antiestrogens. 719 53