Differential effects on bone of estrogen receptor alpha and androgen receptor activation in orchidectomized adult male mice.
Artikel i vetenskaplig tidskrift, 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

Författare

Sofia Movérare-Skrtic

Göteborgs universitet

Katrien Venken

Anna-Lena Eriksson

Göteborgs universitet

Niklas Andersson

Göteborgs universitet

Stanko Skrtic

Göteborgs universitet

Jon Wergedal

Subburaman Mohan

Phil Salmon

Roger Bouillon

Jan-Ake Gustafsson

Dirk Vanderschueren

Claes Ohlsson

Göteborgs universitet

Proceedings of the National Academy of Sciences of the United States of America

0027-8424 (ISSN) 1091-6490 (eISSN)

Vol. 100 23 13573-8

Ämneskategorier

MEDICIN OCH HÄLSOVETENSKAP

DOI

10.1073/pnas.2233084100

PubMed

14573701