{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,18]],"date-time":"2025-10-18T10:02:48Z","timestamp":1760781768024},"reference-count":34,"publisher":"The Endocrine Society","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[1998,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Treatment with the antiestrogen EM-800, at the daily oral dose of 3\u03bc g, 10 \u03bcg, 30 \u03bcg, or 100 \u03bcg for 24 weeks, caused a marked inhibition of uterine and vaginal weight in both intact and ovariectomized mice. Maximal 64% and 41% inhibitions of uterine weight were achieved in intact and ovariectomized animals, respectively. Similar inhibitory effects of EM-800 were observed on vaginal weight with maximal inhibitions of 71% and 35%, in intact and ovariectomized animals, respectively. The pure antiestrogenic activity of EM-800 on the hypothalamo-pituitary-ovarian axis is illustrated by the 76\u201391% increases in ovarian weight observed in intact animals treated with the 10\u2013100 \u03bcg doses of the antiestrogen. Serum 17\u03b2-estradiol was 93% increased at the 100 \u03bcg daily dose of EM-800, whereas serum androstenedione, testosterone, and dihydrotestosterone were 141\u2013713% increased over control at the same dose of the antiestrogen. Serum LH was increased by treatment with EM-800 in intact animals, whereas no effect was observed on the elevated gonadotropin levels in ovariectomized animals. At all doses used in intact animals, the antiestrogen caused a complete disappearance of the glandular elements of the mammary gland, the atrophy being comparable with that observed in ovariectomized mice. The mammary gland of EM-800-treated animals was exclusively composed of an atrophied ductal system lined by atrophied epithelial cells with an absence of lobulo-glandular elements. No effect of the compound was observed on the histology of the mammary gland in ovariectomized animals, thus showing the pure antiestrogenic effect of EM-800 on the mammary gland, as shown also for the uterus, vagina, and hypothalamo-pituitary axis. At histopathology, all doses of EM-800 in intact animals led to a moderate to severe uterine and vaginal atrophy. The uterine atrophy affected both the myometrium and the endometrium. Interestingly, the uterine atrophy achieved in intact animals treated with EM-800 was greater than that observed after ovariectomy alone, thus clearly demonstrating the pure antiestrogenic activity of EM-800. The present data show the highly potent and pure antiestrogenic activity of EM-800 on all parameters measured after 6 months of treatment in both intact and ovariectomized mice, a maximal effect being reached at the daily 10 \u03bcg dose of the antiestrogen in intact animals.<\/jats:p>","DOI":"10.1210\/endo.139.5.5994","type":"journal-article","created":{"date-parts":[[2014,1,8]],"date-time":"2014-01-08T16:09:32Z","timestamp":1389197372000},"page":"2645-2656","source":"Crossref","is-referenced-by-count":12,"title":["Effect of Twenty-Four-Week Treatment with the Antiestrogen EM-800 on Estrogen-Sensitive Parameters in Intact and Ovariectomized Mice"],"prefix":"10.1210","volume":"139","author":[{"given":"Shouqi","family":"Luo","sequence":"first","affiliation":[{"name":"Laboratory of Molecular Endocrinology, Centre Hospitalier de l\u2019Universite\u0301 Laval Research Center, Centre Hospitalier Universitaire de Que\u0301bec et Universite\u0301 Laval, Que\u0301bec, G1V 4G2, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antigone","family":"Sourla","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Endocrinology, Centre Hospitalier de l\u2019Universite\u0301 Laval Research Center, Centre Hospitalier Universitaire de Que\u0301bec et Universite\u0301 Laval, Que\u0301bec, G1V 4G2, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claude","family":"Labrie","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Endocrinology, Centre Hospitalier de l\u2019Universite\u0301 Laval Research Center, Centre Hospitalier Universitaire de Que\u0301bec et Universite\u0301 Laval, Que\u0301bec, G1V 4G2, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sylvain","family":"Gauthier","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Endocrinology, Centre Hospitalier de l\u2019Universite\u0301 Laval Research Center, Centre Hospitalier Universitaire de Que\u0301bec et Universite\u0301 Laval, Que\u0301bec, G1V 4G2, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yves","family":"Merand","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Endocrinology, Centre Hospitalier de l\u2019Universite\u0301 Laval Research Center, Centre Hospitalier Universitaire de Que\u0301bec et Universite\u0301 Laval, Que\u0301bec, G1V 4G2, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alain","family":"Belanger","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Endocrinology, Centre Hospitalier de l\u2019Universite\u0301 Laval Research Center, Centre Hospitalier Universitaire de Que\u0301bec et Universite\u0301 Laval, Que\u0301bec, G1V 4G2, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fernand","family":"Labrie","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Endocrinology, Centre Hospitalier de l\u2019Universite\u0301 Laval Research Center, Centre Hospitalier Universitaire de Que\u0301bec et Universite\u0301 Laval, Que\u0301bec, G1V 4G2, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"80","reference":[{"key":"2020071620494497000_R1","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/S0305-7372(78)80017-6","article-title":"Tamoxifen in advanced breast cancer.","volume":"5","author":"Mouridsen","year":"1978","journal-title":"Cancer Treat Rev"},{"key":"2020071620494497000_R2","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1210\/edrv-8-1-29","article-title":"Estrogenic regulation of growth and polypeptide growth factor secretion in human breast carcinoma.","volume":"8","author":"Dickson","year":"1987","journal-title":"Endocr Rev"},{"key":"2020071620494497000_R3","doi-asserted-by":"crossref","first-page":"8185","DOI":"10.1016\/S0021-9258(17)34379-X","article-title":"Nuclear mechanism of estrogen action. 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principle of protein-dye binding.","volume":"72","author":"Bradford","year":"1976","journal-title":"Anal Biochem"},{"key":"2020071620494497000_R23","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1016\/0022-4731(78)90035-3","article-title":"Effects of estradiol and prolactin on steroid receptor levels in 7,12-dimethylbenz(a)anthracene-induced mammary tumors and uterus in the rat.","volume":"9","author":"Asselin","year":"1978","journal-title":"J Steroid Biochem"},{"key":"2020071620494497000_R24","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/0022-4731(80)90190-9","article-title":"Simultaneous radioimmunoassay of progestins, androgens, and estrogens in adult rat testis.","volume":"13","author":"Be\u0301langer","year":"1980","journal-title":"J Steroid Biochem"},{"key":"2020071620494497000_R25","unstructured":"Be\u0301langer A , LabrieF, MonfetteG, DupontA, CaronS Measurement of non conjugated C-19 steroids as well as C-19 steroid glucuronides in plasma and 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