Disease relevance of NITROMIFENE

• Nitromiphene (NIT; CI 628) is a triarylethylene antiestrogen shown to be effective in treatment of experimental breast cancer [1].
• Effects of the antiestrogens, MER-25 and CI 628, on rat and hamster lordosis [2].
• Effects of ovariectomy, estrogen treatment and CI-628 on food intake and body weight in female rats treated neonatally with gonadal hormones [3].

High impact information on NITROMIFENE

• Metabolism of nitromiphene (CI 628) in the immature female rat: role of gastrointestinal microflora in the biotransformation of a triarylethylene antiestrogen [1].
• The capacity of the antiestrogen CI-628 to activate the estrogen receptor in vitro [4].
• Unexpectedly, the estrogen antagonists enclomiphene, CI-628, tamoxifen, and Lilly 88751 caused increases in both prolactin and growth hormone synthesis at concentrations of about 10(-7) to 10(-6)M after one week of treatment [5].
• The CI-628 dependent changes in protein content and enzyme activities in the uterus were less than half of the EB changes [6].
• In the preoptic area and CM-amygdala, CI-628 resulted in approximately the same changes in CAT and MAO activity as EB [6].

Chemical compound and disease context of NITROMIFENE

• In the analogous behavioral experiments, with antiestrogens injected 2 h prior to an intravenous injection of unesterified estradiol, CI-628 and nafoxidine totally inhibited lordosis responding [7].
• Inhibition of lordosis in rats by the antiestrogen CI-628 in the absence of progesterone [8].
• In Experiment 2, rats receiving CI-628 on only the first 2 of 4 days of EB injections had significantly decreased lordosis scores unless P was also given on the day of testing [8].
• Taken together, the results suggest that the mechanism of action of CI-628 for the inhibition of lordosis does not depend upon its ability to antagonize an estrogen-induced increase in neural progestin receptors [8].

Biological context of NITROMIFENE

• In the first study, rats exhibiting 4-day estrous cycles were injected with various doses (0.02, 0.20, 2.0, and 20 mg/kg) of CI-628 or vehicle at 0900 h on diestrus-2 and proestrus [9].
• The effects of the antiestrogen CI-628 on sexual behavior activated by androgen or estrogen in quail [10].
• Effects of ergocornine and CI-628 on food intake and taste preferences [11].
• Estrogen enhances proliferation and keratin formation in the cervico-vaginal epithelium of immature rats, whereas the estrogen antagonist, CI-628 (Parke-Davis), represses mitosis and induces mucinogenesis [12].
• Hydroxylation of C-4 of triphenylethylene antiestrogens (tamoxifen, CI 628 and U 23,469) largely increases their binding affinity for the estrogen receptor (ER) [13].

Anatomical context of NITROMIFENE

• We have investigated folluclar atresia by giving hypophysectomized immature female rats (HIFR) diethylstibestrol or gonadotrophins with and without the chemical antiestrogen CI-628, making total counts of normal and atretic follicles greater than 125 muM in diameter, and using a simple model to analyze data [14].
• Of the triphenylethylene derivatives and related compounds evaluated, including mixed isomers of tamoxifen and CI 628, the cis (zuclomiphene, ZUC) and trans (enclomiphene) isomers of clomiphene citrate, and a fixed-ring antiestrogen, nafoxidine, only ZUC was able to induce gap junctions in myometrial and serosal cells [15].
• In the present study, blastocyst development and implantation were prevented by instilling the anti-estrogen CI-628 into the uterine lumina of pregnant, ovariectomized, progesterone-treated rabbits [16].
• The maximum level of receptors produced in the HPA cell nuclei following CI-628 treatment was lower than the peak level of nuclear receptors following oestradiol [17].
• The anti-estrogen CN-69, 725-27 produced a much greater inhibition of nuclear [3H]estradiol uptake than CI-628 in the POA-AH, MBH, DMH, dorsal posterior hypothalamus and pituitary samples [18].

Associations of NITROMIFENE with other chemical compounds

• Studies were undertaken to ascertain the effects of structural modification of two well-known antiestrogens (CI-628 and U-11,100A) on their estrogenic and antiestrogenic potencies and temporal patterns of effectiveness in the immature rat uterus [19].
• The effects of CI-628 on the response of the AP to luteinizing hormone-releasing hormone (LHRH) and thyrotropin-releasing hormone (TRH) also were examined [9].
• Oestrogen receptors in cell nuclei of the hypothalamus-preoptic area-amygdala following an injection of oestradiol or the antioestrogen CI-628 [17].
• Effect of neonatal exposure to the antioestrogens nafoxidine and CI-628 upon the development of the uterus in the prepubertal rat [20].
• The effects of nitromifene citrate (CI 628), an antiestrogen, and Flutamide, an antiandrogen, on the ultrastructure and viability of the preovulatory follicle and granulosa cells were examined both in vivo and in vitro [21].

Gene context of NITROMIFENE

• Dose-dependent inhibition of the preovulatory surges of gonadotropins and prolactin by the antiestrogen CI-628: possible sites of action [9].
• The effect of the antiestrogen CI-628 on androgen-induced aggressive behavior in castrated male mice [22].
• Influence of CI-628 (CN-55, 945-27) on estrogen-induced vitellogenin synthesis and on the ultrastructure of hepatocytes in male Xenopus laevis [23].
• CI-628 reduced the 17 beta-HSD activity slightly during the first 5 h [24].
• In contrast, the anti-estrogen's effect on EB-stimulated lordosis was at least equal to the inhibition occurring after CI-628 (IP) given at Hr 0 [25].

Analytical, diagnostic and therapeutic context of NITROMIFENE

• Oestrogen receptors were measured by an exchange assay in cell nuclei of the hypothalamus-preoptic area-amygdala (HPA) of ovariectomized-adrenalectomized (OVX-ADX) rats following an intravenous injection of oestradiol or an antioestrogen, CI-628 [17].
• In ovariectomized rats, only a high dose of CI-628 (24 mg/kg) is able to decrease elevated LH levels observed following castration [26].
• When individual males were placed in a testing arena with a pair of receptive females, only one of which received CI-628, males displayed a preference for the control-group females, as measured by overall copulatory rate [27].

References