title: Reversal of bone loss in mice by nongenotropic signaling of sex steroids.
abstract: We show that sex steroids protect the adult murine skeleton through a mechanism that is distinct from that used to preserve the mass and function of reproductive organs. The classical genotropic actions of sex steroid receptors are dispensable for their bone protective effects, but essential for their effects on reproductive tissues. A synthetic ligand (4-estren-3alpha,17beta-diol) that reproduces the nongenotropic effects of sex steroids, without affecting classical transcription, increases bone mass and strength in ovariectomized females above the level of the estrogen-replete state and is at least as effective as dihydrotestosterone in orchidectomized males, without affecting reproductive organs. Such ligands merit investigation as potential therapeutic alternatives to hormone replacement for osteoporosis in both women and men [corrected].
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, and Center for Osteoporosis and Metabolic Bone Diseases, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
authors.forename: S
authors.initials: S
authors.lastname: Kousteni
authors.forename: J R
authors.initials: JR
authors.lastname: Chen
authors.forename: T
authors.initials: T
authors.lastname: Bellido
authors.forename: L
authors.initials: L
authors.lastname: Han
authors.forename: A A
authors.initials: AA
authors.lastname: Ali
authors.forename: C A
authors.initials: CA
authors.lastname: O'Brien
authors.forename: L
authors.initials: L
authors.lastname: Plotkin
authors.forename: Q
authors.initials: Q
authors.lastname: Fu
authors.forename: A T
authors.initials: AT
authors.lastname: Mancino
authors.forename: Y
authors.initials: Y
authors.lastname: Wen
authors.forename: A M
authors.initials: AM
authors.lastname: Vertino
authors.forename: C C
authors.initials: CC
authors.lastname: Powers
authors.forename: S A
authors.initials: SA
authors.lastname: Stewart
authors.forename: R
authors.initials: R
authors.lastname: Ebert
authors.forename: A M
authors.initials: AM
authors.lastname: Parfitt
authors.forename: R S
authors.initials: RS
authors.lastname: Weinstein
authors.forename: R L
authors.initials: RL
authors.lastname: Jilka
authors.forename: S C
authors.initials: SC
authors.lastname: Manolagas
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D015519:Bone Density / Q000187:drug effects*; D001842:Bone and Bones / Q000187:drug effects* / Q000502:physiology; D001943:Breast Neoplasms / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D019245:Compressive Strength / Q000187:drug effects; D013196:Dihydrotestosterone / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology; D004963:Estrenes / Q000378:metabolism / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D009919:Orchiectomy; D009929:Organ Size / Q000187:drug effects; D010006:Osteoblasts / Q000187:drug effects* / Q000502:physiology; D015675:Osteocalcin / Q000097:blood; D010010:Osteoclasts / Q000187:drug effects* / Q000502:physiology; D010012:Osteogenesis / Q000187:drug effects; D010024:Osteoporosis / Q000188:drug therapy; D010052:Ovariectomy; D011720:Pyrazoles / Q000494:pharmacology; D011960:Receptors, Estrogen / Q000378:metabolism; D012669:Seminal Vesicles / Q000187:drug effects; D014158:Transcription, Genetic / Q000187:drug effects; D014407:Tumor Cells, Cultured; D014599:Uterus / Q000187:drug effects / Q000378:metabolism
chemical_list: C468666:4-estren-3,17-diol; D004963:Estrenes; D011720:Pyrazoles; D011960:Receptors, Estrogen; D013196:Dihydrotestosterone; D015675:Osteocalcin; C031280:pyrazole; D004958:Estradiol