HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Free Full Text (PDF) Free All Versions of this Article: fj.08-113456v1 23/1/232    most recent Alert me when this article is cited Alert me if a correction is posted 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 Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Callewaert, F. Articles by Vanderschueren, D. Search for Related Content PubMed PubMed Citation Articles by Callewaert, F. Articles by Vanderschueren, D.

Differential regulation of bone and body composition in male mice with combined inactivation of androgen and estrogen receptor-

Filip Callewaert^*, Katrien Venken^*, Jill Ophoff^*, Karel De Gendt^*, Antonia Torcasio, G. Harry van Lenthe, Hans Van Oosterwyck, Steven Boonen^*, Roger Bouillon^*, Guido Verhoeven^* and Dirk Vanderschueren^*,1

^* Laboratory for Experimental Medicine and Endocrinology, Department of Experimental Medicine, and

Division of Biomechanics and Engineering Design, Department of Mechanical Engineering, Katholieke Universiteit Leuven, Leuven, Belgium

¹ Laboratory for Experimental Medicine and Endocrinology, Herestraat 49, B-3000 Leuven, Belgium. E-mail: dirk.vanderschueren{at}uz.kuleuven.be

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 (ER) following aromatization of androgens into estrogens. To assess the differential action of AR and ER pathways on bone and body composition, AR-ER double-knockout mice were generated and characterized. AR disruption decreased trabecular bone mass, whereas ER disruption had no additional effect on the AR-dependent trabecular bone loss. In contrast, combined AR and ER inactivation additionally reduced cortical bone and muscle mass compared with either AR or ER disruption alone. ER 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 ER activation, however, are needed to optimize the acquisition of cortical bone and muscle mass. ER activation alone is sufficient for the regulation of fat mass. Our findings clearly define the relative importance of AR and ER signaling on trabecular and cortical bone mass as well as body composition in male mice.—Callewaert, F., Venken, K., Ophoff, J., De Gendt, K., Torcasio, A., van Lenthe, G. H., Van Oosterwyck, H., Boonen, S., Bouillon, R., Verhoeven, G., Vanderschueren, D. Differential regulation of bone and body composition in male mice with combined inactivation of androgen and estrogen receptor-.

Key Words: sex steroid action • trabecular bone • cortical bone • bone strength • muscle and fat mass

This article has been cited by other articles:

				H. E. MacLean and D. J. Handelsman Unraveling Androgen Action in Muscle: Genetic Tools Probing Cellular Mechanisms Endocrinology, August 1, 2009; 150(8): 3437 - 3439. [Full Text] [PDF]

				J. Ophoff, K. Van Proeyen, F. Callewaert, K. De Gendt, K. De Bock, A. Vanden Bosch, G. Verhoeven, P. Hespel, and D. Vanderschueren Androgen Signaling in Myocytes Contributes to the Maintenance of Muscle Mass and Fiber Type Regulation But Not to Muscle Strength or Fatigue Endocrinology, August 1, 2009; 150(8): 3558 - 3566. [Abstract] [Full Text] [PDF]