title: Estren is a selective estrogen receptor modulator with transcriptional activity.
abstract: It was recently reported that the synthetic compound estren increases bone mass without affecting reproductive organs or classic transcription. The aim of the present study was to further characterize the in vivo and in vitro effects of estren. We demonstrate that estren is a selective estrogen receptor modulator (SERM) with a strong effect on thymus, a moderate effect on uterus and trabecular bone, but no major effect on fat or cortical bone in 11-month-old ovariectomized mice. The effect of estren on trabecular bone and uterus is mediated via estrogen receptors (ERs) because no effect is seen in ER double-inactivated mice. Furthermore, with the use of ERalpha- and ERbeta-expressing reporter cell lines, we demonstrate that estren displays an agonistic effect on transcriptional activity of an estrogen-responsive element-driven reporter gene with a degree of agonism similar to that of 17beta-estradiol for both ERalpha and ERbeta. Thus, estren has the capacity to exert genomic effects via both ERalpha and ERbeta. We conclude, in contrast to what was previously reported by others, that estren is a SERM with transcriptional activity.
authors.affiliation: Department of Internal Medicine, Division of Endocrinology, Gröna Stråket 8, 413 45 Gothenburg, Sweden.
authors.forename: Sofia
authors.initials: S
authors.lastname: Movérare
authors.forename: Johanna
authors.initials: J
authors.lastname: Dahllund
authors.forename: Niklas
authors.initials: N
authors.lastname: Andersson
authors.forename: Ulrika
authors.initials: U
authors.lastname: Islander
authors.forename: Hans
authors.initials: H
authors.lastname: Carlsten
authors.forename: Jan-Ake
authors.initials: JA
authors.lastname: Gustafsson
authors.forename: Stefan
authors.initials: S
authors.lastname: Nilsson
authors.forename: Claes
authors.initials: C
authors.lastname: Ohlsson
mesh_terms: D000818:Animals; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004963:Estrenes / Q000378:metabolism / Q000494:pharmacology*; D020847:Estrogen Receptor Modulators / Q000378:metabolism / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010052:Ovariectomy; D011960:Receptors, Estrogen / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects / Q000502:physiology*; D014599:Uterus / Q000187:drug effects / Q000378:metabolism
chemical_list: C468666:4-estren-3,17-diol; D004963:Estrenes; D020847:Estrogen Receptor Modulators; D011960:Receptors, Estrogen