Testosterone and the Male Skeleton: A Dual Mode of Action
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 estradio...
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| Format: | Article |
| Language: | English |
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Wiley
2011-01-01
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| Series: | Journal of Osteoporosis |
| Online Access: | http://dx.doi.org/10.4061/2011/240328 |
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| author | Mieke Sinnesael Steven Boonen Frank Claessens Evelien Gielen Dirk Vanderschueren |
| author_facet | Mieke Sinnesael Steven Boonen Frank Claessens Evelien Gielen Dirk Vanderschueren |
| author_sort | Mieke Sinnesael |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-5ed83841e55a4c4899d18eef1731e535 |
| institution | OA Journals |
| issn | 2042-0064 |
| language | English |
| publishDate | 2011-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Osteoporosis |
| spelling | doaj-art-5ed83841e55a4c4899d18eef1731e5352025-08-20T02:05:09ZengWileyJournal of Osteoporosis2042-00642011-01-01201110.4061/2011/240328240328Testosterone and the Male Skeleton: A Dual Mode of ActionMieke Sinnesael0Steven Boonen1Frank Claessens2Evelien Gielen3Dirk Vanderschueren4Experimental Medicine and Endocrinology, Department of Experimental Medicine, K. U. Leuven, 300 Leuven, BelgiumDivision of Geriatric Medicine, Leuven University Hospital, Leuven, 300 Leuven, BelgiumMolecular Endocrinology Laboratory, Department of Molecular Cell Biology, K. U. Leuven, 300 Leuven, BelgiumDivision of Geriatric Medicine, Leuven University Hospital, Leuven, 300 Leuven, BelgiumExperimental Medicine and Endocrinology, Department of Experimental Medicine, K. U. Leuven, 300 Leuven, BelgiumTestosterone 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.http://dx.doi.org/10.4061/2011/240328 |
| spellingShingle | Mieke Sinnesael Steven Boonen Frank Claessens Evelien Gielen Dirk Vanderschueren Testosterone and the Male Skeleton: A Dual Mode of Action Journal of Osteoporosis |
| title | Testosterone and the Male Skeleton: A Dual Mode of Action |
| title_full | Testosterone and the Male Skeleton: A Dual Mode of Action |
| title_fullStr | Testosterone and the Male Skeleton: A Dual Mode of Action |
| title_full_unstemmed | Testosterone and the Male Skeleton: A Dual Mode of Action |
| title_short | Testosterone and the Male Skeleton: A Dual Mode of Action |
| title_sort | testosterone and the male skeleton a dual mode of action |
| url | http://dx.doi.org/10.4061/2011/240328 |
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