Differential effects on bone of estrogen receptor alpha and androgen receptor activation in orchidectomized adult male mice.
Journal article, 2003
Androgens may regulate the male skeleton either directly by stimulation of the androgen receptor (AR) or indirectly by aromatization of androgens into estrogens and, thereafter, by stimulation of the estrogen receptors (ERs). To directly compare the effect of ER activation on bone in vivo with the effect of AR activation, 9-month-old orchidectomized wild-type and ER-inactivated mice were treated with the nonaromatizable androgen 5alpha-dihydrotestosterone, 17beta-estradiol, or vehicle. Both ERalpha and AR but not ERbeta activation preserved the amount of trabecular bone. ERalpha activation resulted both in a preserved thickness and number of trabeculae. In contrast, AR activation exclusively preserved the number of trabeculae, whereas the thickness of the trabeculae was unaffected. Furthermore, the effects of 17beta-estradiol could not be mediated by the AR, and the effects of 5alpha-dihydrotestosterone were increased rather than decreased in ER-inactivated mice. ERalpha, but not AR or ERbeta, activation resulted in preserved thickness, volumetric density, and mechanical strength of the cortical bone. ERalpha activation increased serum levels of insulin-like growth factor I, which were positively correlated with all the cortical and trabecular bone parameters that were specifically preserved by ERalpha activation but not by AR activation, suggesting that insulin-like growth factor I might mediate these effects of ERalpha activation. Thus, the in vivo bone-sparing effect of ERalpha activation is distinct from the bone-sparing effect of AR activation in adult male mice. Because these two pathways are clearly distinct from each other, one may speculate that a combined treatment of selective ER modulators and selective AR modulators might be beneficial in the treatment of osteoporosis.
Estradiol
Prostate
Enzyme-Linked Immunosorbent Assay
Tomography
Animals
Estrogen
Receptors
Bone and Bones
Estrogen Receptor alpha
Androgen
Receptors
Dihydrotestosterone
Osteoporosis
metabolism
Insulin-Like Growth Factor I
Time Factors
Female
X-Ray Computed
Male
pharmacology
metabolism
Mice
metabolism
biosynthesis
blood
physiology
Heterozygote
pharmacology
physiology
Osteocalcin
Author
Sofia Movérare-Skrtic
University of Gothenburg
Katrien Venken
Anna-Lena Eriksson
University of Gothenburg
Niklas Andersson
University of Gothenburg
Stanko Skrtic
University of Gothenburg
Jon Wergedal
Subburaman Mohan
Phil Salmon
Roger Bouillon
Jan-Ake Gustafsson
Dirk Vanderschueren
Claes Ohlsson
University of Gothenburg
Proceedings of the National Academy of Sciences of the United States of America
0027-8424 (ISSN) 1091-6490 (eISSN)
Vol. 100 23 13573-8Subject Categories
MEDICAL AND HEALTH SCIENCES
DOI
10.1073/pnas.2233084100
PubMed
14573701