Impact on Bone of an Estrogen Receptor-α Gene Loss of Function Mutation

Abstract

Homozygous ER-alpha disruption markedly affects bone growth, mineral content, and structure but not periosteal circumference. ER-alpha heterozygosity appears to not impair spine aBMD.

The role of estrogen receptor-α and its activation function-1 for growth plate closure in female mice

“…We have previously shown that old female mice with a cartilage-specific ER␣ inactivation also have an increased bone length, emphasizing that local ER␣ is of importance for age-dependent reduction of longitudinal bone growth (2). Our present study together with these previous human and mouse studies strongly suggest that ER␣ is the dominant ER for the normal age-dependent reduction and cessation of longitudinal bone growth observed in mouse and humans, respectively, and that this effect is mediated via growth plate-located ER␣ (2,30,31).…”

“…The estrogen-resistant man did not respond to E 2 treatment, but at the age of 33.5 yr his growth plates were nearly fused. This suggests that it is possible to attain growth plate closure even without a functional ER␣ in humans, but that this fusion is clearly delayed (31). There seems to be species differences regarding ER␣-independent growth plate fusion, since elderly female ER␣ Ϫ/Ϫ mice still have open growth plates.…”

“…This man experienced a continued growth long into adulthood, but at the age of 33.5 yr his growth plates were nearly fused. This indicates that ER␣ is the main mediator of the estrogenic effects on growth plate closure in humans (30,31). It should be emphasized that the growth plate physiology differs between humans and rodents, since the growth plates do not fuse directly after sexual maturation in rodents and, therefore, one should be cautious when extrapolating data on humans from mouse models.…”

The DHEA metabolite 7β-hydroxy-epiandrosterone exerts anti-estrogenic effects on breast cancer cell lines

“…Tissu Rôle physiologique Pathologie • Maintien de la balance résorption / formation osseuse (Khosla, 2008;Smith et al, 2008 ) • Maturation de l'os / croissance osseuse à la puberté (Zirilli et al, 2008 (Zirilli et al, 2008;Maffei et al, 2004 ) Sein • Développement de la glande mammaire (REα) (Nilsson et Gustaffson, 2002 • Cancer du sein hormono-dépendant protection par le REβ (Bardin et al, 2004 ) rôle pro-prolifératif du REα (Lazennec et al, 2001 ) • Apprentissage, mémoire, comportement, reproduction, neurogenèse, plasticité synaptique, protection neuronale (Gillies et McArthur, 2010 ) • Maladie d'Alzheimer (Carroll et Picke, 2008 ) protection par REα dans l'hippocampe et l'amygdale protection par REβ dans le cortex frontal et l'amygdale • Maladie de Parkinson protection par REα (Brann et 2007;Gillies et McArthur, 2010 ) • Sclérose multiple protection par REα (Vegeto et al, 2008 ) protection par REβ (Tiwari-Woodruff, 2009 ) Appareil reproducteur…”

“…• Infertilité des femelles et des mâles KO pour le REα (Dupont et al, 2000;Nilsson et Gustaffson, 2011 (Khosla, 2008;Smith et al, 2008 ) …”