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Göteborgs universitets publikationer

SERMs have substance-specific effects on bone, and these effects are mediated via ER alpha AF-1 in female mice

Författare och institution:
A. E. Borjesson (-); Helen H. Farman (Centre for Bone and Arthritis Research); Sofia Movérare-Skrtic (Centre for Bone and Arthritis Research); Cecilia Engdahl (Centre for Bone and Arthritis Research); M. C. Antal (-); A. Koskela (-); J. Tuukkanen (-); Hans Carlsten (Centre for Bone and Arthritis Research); A. Krust (-); P. Chambon (-); Klara Sjögren (Centre for Bone and Arthritis Research); Marie K Lagerquist (Centre for Bone and Arthritis Research); Sara H Windahl (Centre for Bone and Arthritis Research); Claes Ohlsson (Centre for Bone and Arthritis Research)
Publicerad i:
American Journal of Physiology-Endocrinology and Metabolism, 310 ( 11 ) s. E912-E918
Artikel, refereegranskad vetenskaplig
Sammanfattning (abstract):
The bone-sparing effect of estrogens is mediated primarily via estrogen receptor (ER)alpha, which stimulates gene transcription through activation function (AF)-1 and AF-2. The role of ER alpha AF-1 for the estradiol (E-2) effects is tissue specific. The selective ER modulators (SERMs) raloxifene (Ral), lasofoxifene (Las), and bazedoxifene (Bza) can be used to treat postmenopausal osteoporosis. They all reduce the risk for vertebral fractures, whereas Las and partly Bza, but not Ral, reduce the risk for nonvertebral fractures. Here, we have compared the tissue specificity of Ral, Las, and Bza and evaluated the role of ER alpha AF-1 for the effects of these SERMs, with an emphasis on bone parameters. We treated ovariectomized (OVX) wild-type (WT) mice and OVX mice lacking ER alpha AF-1 (ER alpha AF-1(0)) with E-2, Ral, Las, or Bza. All three SERMs increased trabecular bone mass in the axial skeleton. In the appendicular skeleton, only Las increased the trabecular bone volume/tissue volume and trabecular number, whereas both Ral and Las increased the cortical bone thickness and strength. However, Ral also increased cortical porosity. The three SERMs had only a minor effect on uterine weight. Notably, all evaluated effects of these SERMs were absent in ovx ER alpha AF-1(0) mice. In conclusion, all SERMs had similar effects on axial bone mass. However, the SERMs had slightly different effects on the appendicular skeleton since only Las increased the trabecular bone mass and only Ral increased the cortical porosity. Importantly, all SERM effects require a functional ER alpha AF-1 in female mice. These results could lead to development of more specific treatments for osteoporosis.
Ämne (baseras på Högskoleverkets indelning av forskningsämnen):
Klinisk medicin
estrogen receptor, estrogen, selective estrogen receptor modulators, mouse, osteoporosis, activation function-1 of estrogen receptor-alpha, estrogen-receptor-alpha, transcriptional activation functions, hormone, replacement therapy, cortical bone, postmenopausal women, fracture-toughness, serum estradiol, increased risk, breast-cancer, distal radius
Postens nummer:
Posten skapad:
2016-07-04 10:59

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