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Journal of Osteoporosis Volume 2011 ,20111-07-25
Testosterone and the Male Skeleton: A Dual Mode of Action
Research Article
Mieke Sinnesael 1 Steven Boonen 2 , 3 , 4 Frank Claessens 5 Evelien Gielen 2 , 3 , 4 Dirk Vanderschueren 1 , 4 , 6
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DOI:10.4061/2011/240328
Received 2011-04-13, accepted for publication 2011-07-04, Published 2011-07-04
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摘要

Testosterone is an important hormone for both bone gain and maintenance in men. Hypogonadal men have accelerated bone turnover and increased fracture risk. In these men, administration of testosterone inhibits bone resorption and maintains bone mass. Testosterone, however, is converted into estradiol via aromatization in many tissues including male bone. The importance of estrogen receptor alpha activation as well of aromatization of androgens into estrogens was highlighted by a number of cases of men suffering from an inactivating mutation in the estrogen receptor alpha or in the aromatase enzyme. All these men typically had low bone mass, high bone turnover and open epiphyses. In line with these findings, cohort studies have confirmed that estradiol contributes to the maintenance of bone mass after reaching peak bone mass, with an association between estradiol and fractures in elderly men. Recent studies in knock-out mice have increased our understanding of the role of androgens and estrogens in different bone compartments. Estrogen receptor activation, but not androgen receptor activation, is involved in the regulation of male longitudinal appendicular skeletal growth in mice. Both the androgen and the estrogen receptor can independently mediate the cancellous bone-sparing effects of sex steroids in male mice. Selective KO studies of the androgen receptor in osteoblasts in male mice suggest that the osteoblast in the target cell for androgen receptor mediated maintenance of trabecular bone volume and coordination of bone matrix synthesis and mineralization. Taken together, both human and animal studies suggest that testosterone has a dual mode of action on different bone surfaces with involvement of both the androgen and estrogen receptor.

授权许可

Copyright © 2011 Mieke Sinnesael et al. 2011
This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

图表

Metabolism of sex steroids. (i) Testosterone (T), that is secreted by the testes, can directly act on its receptor, the androgen receptor (AR), present in bone cells. (ii) T can also be converted locally to dihydrotestosterone (DHT) by 5α-reductase. (iii) In addition, T can undergo aromatization to 17β-estradiol (E2) by aromatase. E2acts on one or both estrogen receptors (ERα or ERβ). (iv) The adrenals secrete C19 androgens including dehydroepiandrosterone (DHEA) that can also be converted to (v) estrone (E1) and E2by aromatase, 17β-hydroxysteroid dehydrogenase (17β-HSD), and 3β-HSD or to T by 17β-HSD and/or 3β-HSD. (vi) In men and women, T and E2are predominantly bound to sex hormone binding globulin (SHBG), synthesized by the liver.

通讯作者

Dirk Vanderschueren.Experimental Medicine and Endocrinology, Department of Experimental Medicine, K. U. Leuven, 300 Leuven, Belgium, kuleuven.be;Leuven University Centre for Metabolic Bone Diseases, 300 Leuven, Belgium, kuleuven.be;Laboratory for Experimental Medicine and Endocrinology, Leuven University Hospital, Herestraat 49, 300 Leuven, Belgium, kuleuven.be.dirk.vanderschueren@uz.kuleuven.be

推荐引用方式

Mieke Sinnesael,Steven Boonen,Frank Claessens,Evelien Gielen,Dirk Vanderschueren. Testosterone and the Male Skeleton: A Dual Mode of Action. Journal of Osteoporosis ,Vol.2011(20111)

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