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Roles of transactivating functions 1 and 2 of estrogen receptor-alpha in bone.

Börjesson, Anna E (author)
Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för invärtesmedicin,Centre for Bone and Arthritis Research,Institute of Medicine, Department of Internal Medicine
Windahl, Sara H, 1971 (author)
Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för invärtesmedicin,Centre for Bone and Arthritis Research,Institute of Medicine, Department of Internal Medicine
Lagerquist, Marie (author)
Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för invärtesmedicin,Centre for Bone and Arthritis Research,Institute of Medicine, Department of Internal Medicine
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Engdahl, Cecilia, 1983 (author)
Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning,Centre for Bone and Arthritis Research,Institute of Medicine, Department of Rheumatology and Inflammation Research
Frenkel, B (author)
Movérare-Skrtic, Sofia (author)
Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för invärtesmedicin,Centre for Bone and Arthritis Research,Institute of Medicine, Department of Internal Medicine
Sjögren, Klara, 1970 (author)
Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för invärtesmedicin,Centre for Bone and Arthritis Research,Institute of Medicine, Department of Internal Medicine
Kindblom, Jenny, 1971 (author)
Gothenburg University,Göteborgs universitet,Centre for Bone and Arthritis Research
Stubelius, Alexandra, 1983 (author)
Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning,Centre for Bone and Arthritis Research,Institute of Medicine, Department of Rheumatology and Inflammation Research
Islander, Ulrika, 1975 (author)
Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning,Centre for Bone and Arthritis Research,Institute of Medicine, Department of Rheumatology and Inflammation Research
Antal, Mc (author)
Krust, A (author)
Chambon, P (author)
Ohlsson, Claes, 1965 (author)
Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för invärtesmedicin,Centre for Bone and Arthritis Research,Institute of Medicine, Department of Internal Medicine
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 (creator_code:org_t)
2011-03-28
2011
English.
In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424. ; 108:15, s. 6288-6293
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  • Journal article (peer-reviewed)
Abstract Subject headings
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  • The bone-sparing effect of estrogen is primarily mediated via estrogen receptor-α (ERα), which stimulates target gene transcription through two activation functions (AFs), AF-1 in the N-terminal and AF-2 in the ligand binding domain. To evaluate the role of ERα AF-1 and ERα AF-2 for the effects of estrogen in bone in vivo, we analyzed mouse models lacking the entire ERα protein (ERα(-/-)), ERα AF-1 (ERαAF-1(0)), or ERα AF-2 (ERαAF-2(0)). Estradiol (E2) treatment increased the amount of both trabecular and cortical bone in ovariectomized (OVX) WT mice. Neither the trabecular nor the cortical bone responded to E2 treatment in OVX ERα(-/-) or OVX ERαAF-2(0) mice. OVX ERαAF-1(0) mice displayed a normal E2 response in cortical bone but no E2 response in trabecular bone. Although E2 treatment increased the uterine and liver weights and reduced the thymus weight in OVX WT mice, no effect was seen on these parameters in OVX ERα(-/-) or OVX ERαAF-2(0) mice. The effect of E2 in OVX ERαAF-1(0) mice was tissue-dependent, with no or weak E2 response on thymus and uterine weights but a normal response on liver weight. In conclusion, ERα AF-2 is required for the estrogenic effects on all parameters evaluated, whereas the role of ERα AF-1 is tissue-specific, with a crucial role in trabecular bone and uterus but not cortical bone. Selective ER modulators stimulating ERα with minimal activation of ERα AF-1 could retain beneficial actions in cortical bone, constituting 80% of the skeleton, while minimizing effects on reproductive organs.

Subject headings

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

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