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Role of the androgen receptor in skeletal homeostasis: the androgen-resistant testicular feminized male mouse model.

Vandenput, Liesbeth, 1974 (author)
Gothenburg University,Göteborgs universitet,Institutionen för invärtesmedicin, Avdelningen för internmedicin,Institute of Internal Medicine, Dept of Medicine
Swinnen, Johannes V (author)
Boonen, Steven (author)
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Van Herck, Erik (author)
Erben, Reinhold G (author)
Bouillon, Roger (author)
Vanderschueren, Dirk (author)
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 (creator_code:org_t)
2004
2004
English.
In: Journal of bone and mineral research. - 0884-0431. ; 19:9, s. 1462-70
  • Journal article (peer-reviewed)
Abstract Subject headings
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  • The role of androgen receptor-mediated androgen action on bone was investigated in testicular feminized male (Tfm) mice. Cortical bone was found to be unresponsive to testosterone (T) in orchidectomized Tfm mice, whereas cortical thickness as well as trabecular BMD and structure were fully maintained by T in the corresponding Tabby control mice. These data show an essential role for androgen receptor-mediated androgen action in periosteal bone formation. INTRODUCTION: Androgens can affect the male skeleton both directly-through activation of the androgen receptor (AR)-and indirectly-through stimulation of estrogen receptors after aromatization. We assessed the importance of AR-mediated androgen action on bone in a mouse model of androgen resistance. MATERIALS AND METHODS: Eight-week-old androgen-resistant testicular feminized male (Tfm) and Tabby control mice were orchidectomized (ORX) and treated for 4 weeks with a slow-release testosterone (T) pellet (delivering 167 microg/day) or a placebo pellet. A comprehensive analysis of the skeletal effects of androgen deficiency and replacement was performed using histomorphometry, QCT, and biochemical assessment of bone turnover. RESULTS: As expected, T increased trabecular BMD, volume, number, and width in ORX Tabby mice. In ORX Tfm mice, however, T had less effect on trabecular BMD and no effect on trabecular bone structure. T action on trabecular bone was associated with opposite changes in bone turnover: trabecular and endocortical bone turnover and serum levels of osteocalcin were all reduced by T in ORX Tabby mice, but not in ORX Tfm mice. T also increased cortical thickness (+16%), area, and density in ORX Tabby mice, but not in Tfm mice, resulting in greater bone strength in the Tabby control strain. The positive effects of T on cortical bone reflected a stimulatory effect on periosteal bone formation (+137%), which was again absent in Tfm mice. CONCLUSIONS: These data show that, in male mice, AR-mediated T action is essential for periosteal bone formation and contributes to trabecular bone maintenance.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)

Keyword

Androgen-Insensitivity Syndrome
metabolism
Androgens
metabolism
pharmacology
Animals
Bone Density
Bone and Bones
drug effects
physiology
Disease Models
Animal
Female
Femur
anatomy & histology
Homeostasis
drug effects
physiology
Hormone Replacement Therapy
Male
Mice
Mice
Inbred C57BL
Mice
Mutant Strains
Models
Animal
Orchiectomy
Phenotype
Receptors
Androgen
metabolism
Testis
drug effects
metabolism

Publication and Content Type

ref (subject category)
art (subject category)

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