title: Differential regulation of bone and body composition in male mice with combined inactivation of androgen and estrogen receptor-alpha.
abstract: Osteoporosis and muscle frailty are important health problems in elderly men and may be partly related to biological androgen activity. This androgen action can be mediated directly through stimulation of the androgen receptor (AR) or indirectly through stimulation of estrogen receptor-alpha (ERalpha) following aromatization of androgens into estrogens. To assess the differential action of AR and ERalpha pathways on bone and body composition, AR-ERalpha double-knockout mice were generated and characterized. AR disruption decreased trabecular bone mass, whereas ERalpha disruption had no additional effect on the AR-dependent trabecular bone loss. In contrast, combined AR and ERalpha inactivation additionally reduced cortical bone and muscle mass compared with either AR or ERalpha disruption alone. ERalpha inactivation--in the presence or absence of AR--increased fat mass. We demonstrate that AR activation is solely responsible for the development and maintenance of male trabecular bone mass. Both AR and ERalpha activation, however, are needed to optimize the acquisition of cortical bone and muscle mass. ERalpha activation alone is sufficient for the regulation of fat mass. Our findings clearly define the relative importance of AR and ERalpha signaling on trabecular and cortical bone mass as well as body composition in male mice.
authors.affiliation: Laboratory for Experimental Medicine and Endocrinology, Department of Experimental Medicine, Katholieke Universiteit Leuven, Leuven, Belgium.
authors.forename: Filip
authors.initials: F
authors.lastname: Callewaert
authors.forename: Katrien
authors.initials: K
authors.lastname: Venken
authors.forename: Jill
authors.initials: J
authors.lastname: Ophoff
authors.forename: Karel
authors.initials: K
authors.lastname: De Gendt
authors.forename: Antonia
authors.initials: A
authors.lastname: Torcasio
authors.forename: G Harry
authors.initials: GH
authors.lastname: van Lenthe
authors.forename: Hans
authors.initials: H
authors.lastname: Van Oosterwyck
authors.forename: Steven
authors.initials: S
authors.lastname: Boonen
authors.forename: Roger
authors.initials: R
authors.lastname: Bouillon
authors.forename: Guido
authors.initials: G
authors.lastname: Verhoeven
authors.forename: Dirk
authors.initials: D
authors.lastname: Vanderschueren
mesh_terms: D000375:Aging; D000818:Animals; D001823:Body Composition / Q000235:genetics* / Q000502:physiology; D015519:Bone Density / Q000235:genetics* / Q000502:physiology; D001842:Bone and Bones / Q000378:metabolism*; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010024:Osteoporosis / Q000378:metabolism; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism*
chemical_list: D047628:Estrogen Receptor alpha; D011944:Receptors, Androgen