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The role of estroge...
The role of estrogen receptor-alpha and its activation function-1 for growth plate closure in female mice
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- Börjesson, Anna E (author)
- Gothenburg University,Göteborgs universitet,Centre for Bone and Arthritis Research
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- Windahl, Sara H, 1971 (author)
- Gothenburg University,Göteborgs universitet,Centre for Bone and Arthritis Research
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Karimian, E. (author)
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Eriksson, E. E. (author)
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- Lagerquist, Marie (author)
- Gothenburg University,Göteborgs universitet,Centre for Bone and Arthritis Research
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- Engdahl, Cecilia, 1983 (author)
- Gothenburg University,Göteborgs universitet,Centre for Bone and Arthritis Research
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Antal, M. C. (author)
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Krust, A. (author)
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Chambon, P. (author)
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Savendahl, L. (author)
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- Ohlsson, Claes, 1965 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för invärtesmedicin och klinisk nutrition,Centre for Bone and Arthritis Research,Institute of Medicine, Department of Internal Medicine and Clinical Nutrition
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(creator_code:org_t)
- American Physiological Society, 2012
- 2012
- English.
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In: American Journal of Physiology-Endocrinology and Metabolism. - : American Physiological Society. - 0193-1849 .- 1522-1555. ; 302:11
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Abstract
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- Borjesson AE, Windahl SH, Karimian E, Eriksson EE, Lagerquist MK, Engdahl C, Antal MC, Krust A, Chambon P, Savendahl L, Ohlsson C. The role of estrogen receptor-alpha and its activation function-1 for growth plate closure in female mice. Am J Physiol Endocrinol Metab 302: E1381-E1389, 2012. First published March 13, 2012; doi:10.1152/ajpendo.00646.2011.-High estradiol levels in late puberty induce growth plate closure and thereby cessation of growth in humans. In mice, the growth plates do not fuse after sexual maturation, but old mice display reduced longitudinal bone growth and high-dose estradiol treatment induces growth plate closure. Estrogen receptor (ER)-alpha stimulates gene transcription via two activation functions (AFs), AF-1 and AF-2. To evaluate the role of ER alpha and its AF-1 for age-dependent reduction in longitudinal bone growth and growth plate closure, female mice with inactivation of ER alpha (ER alpha(-/-)) or ER alpha AF-1 (ER alpha AF-1(0)) were evaluated. Old (16- to 19-mo-old) female ER alpha(-/-) mice showed continued substantial longitudinal bone growth, resulting in longer bones (tibia: +8.3%, P < 0.01) associated with increased growth plate height (+18%, P < 0.05) compared with wild-type (WT) mice. In contrast, the longitudinal bone growth ceased in old ER alpha AF-1(0) mice (tibia: -4.9%, P < 0.01). Importantly, the proximal tibial growth plates were closed in all old ER alpha AF-1(0) mice while they were open in all WT mice. Growth plate closure was associated with a significantly altered balance between chondrocyte proliferation and apoptosis in the growth plate. In conclusion, old female ER alpha(-/-) mice display a prolonged and enhanced longitudinal bone growth associated with increased growth plate height, resembling the growth phenotype of patients with inactivating mutations in ER alpha or aromatase. In contrast, ER alpha AF-1 deletion results in a hyperactive ER alpha, altering the chondrocyte proliferation/apoptosis balance, leading to growth plate closure. This suggests that growth plate closure is induced by functions of ER alpha that do not require AF-1 and that ER alpha AF-1 opposes growth plate closure.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
Keyword
- estrogen receptor-alpha
- growth plate
- estrogen
- chondrocytes
- bone-mineral density
- precocious puberty
- epiphyseal fusion
- skeletal
- growth
- er-alpha
- aromatase
- gene
- beta
- estradiol
- mutation
Publication and Content Type
- ref (subject category)
- art (subject category)
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Börjesson, Anna ...
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Windahl, Sara H, ...
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Karimian, E.
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Eriksson, E. E.
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Lagerquist, Mari ...
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Engdahl, Cecilia ...
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Antal, M. C.
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Krust, A.
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Chambon, P.
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Savendahl, L.
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Ohlsson, Claes, ...
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University of Gothenburg