This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Luo, S. Articles by Labrie, F. Search for Related Content PubMed PubMed Citation Articles by Luo, S. Articles by Labrie, F.

Effect of Twenty-Four-Week Treatment with the Antiestrogen EM-800 on Estrogen-Sensitive Parameters in Intact and Ovariectomized Mice

Laboratory of Molecular Endocrinology, Centre Hospitalier de l’Université Laval Research Center, Centre Hospitalier Universitaire de Québec et Université Laval, Québec, G1V 4G2, Canada

Address all correspondence and requests for reprints to: Prof. Fernand Labrie, Laboratory of Molecular Endocrinology, Centre Hospitalier de l’Université Laval Research Center, 2705 Laurier Boulevard, Québec, G1V 4G2, Canada. E-mail: Fernand.Labrie{at}crchul.ulaval.ca

Treatment with the antiestrogen EM-800, at the daily oral dose of 3 µg, 10 µg, 30 µg, or 100 µg 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 76–91% increases in ovarian weight observed in intact animals treated with the 10–100 µg doses of the antiestrogen. Serum 17ß-estradiol was 93% increased at the 100 µg daily dose of EM-800, whereas serum androstenedione, testosterone, and dihydrotestosterone were 141–713% 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 µg dose of the antiestrogen in intact animals.

This article has been cited by other articles:

				T. L. Mazzuco, O. Chabre, J.-J. Feige, and M. Thomas Aberrant Expression of Human Luteinizing Hormone Receptor by Adrenocortical Cells Is Sufficient to Provoke Both Hyperplasia and Cushing's Syndrome Features J. Clin. Endocrinol. Metab., January 1, 2006; 91(1): 196 - 203. [Abstract] [Full Text] [PDF]