Fiche publication
Date publication
juin 2012
Auteurs
Membres identifiés du Cancéropôle Est :
Pr CHAMBON Pierre
Tous les auteurs :
Borjesson AE, Windahl SH, Karimian E, Eriksson EE, Lagerquist MK, Engdahl C, Antal MC, Krust A, Chambon P, Savendahl L, Ohlsson C
Lien Pubmed
Résumé
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 ERalpha and its AF-1 for age-dependent reduction in longitudinal bone growth and growth plate closure, female mice with inactivation of ERalpha (ERalpha(-/-)) or ERalphaAF-1 (ERalphaAF-1(0)) were evaluated. Old (16- to 19-mo-old) female ERalpha(-/-) 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 ERalphaAF-1(0) mice (tibia: -4.9%, P < 0.01). Importantly, the proximal tibial growth plates were closed in all old ERalphaAF-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 ERalpha(-/-) 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 ERalpha or aromatase. In contrast, ERalphaAF-1 deletion results in a hyperactive ERalpha, altering the chondrocyte proliferation/apoptosis balance, leading to growth plate closure. This suggests that growth plate closure is induced by functions of ERalpha that do not require AF-1 and that ERalphaAF-1 opposes growth plate closure.
Référence
Am J Physiol Endocrinol Metab. 2012 Jun;302(11):E1381-9
