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Endocrine Abstracts (2012) 29 S12.3

ICEECE2012 Symposia Determinants of peak bone mass (3 abstracts)

Estrogens as regulators of bone growth and bone mass

C. Ohlsson 1, , S. Windahl 1, , M. Lagerquist 1, , L. Vandenput 1, & A. Börjesson 1,


1Gothenburg University, Gothenburg, Sweden; 2Medicine, Sahgrenska Academy, Gothenburg, Sweden.


Estrogens regulate bone growth and bone mass mainly via estrogen receptor-α (ERα). In addition, the anabolic effect of mechanical loading on cortical bone requires ERα. This lecture summarizes some recent findings characterizing the primary target cells and the crucial ERα domains for the mediation of these estrogenic effects on the skeleton.

Mice with complete inactivation of ERα continue to grow throughout life associated with increased growth plate height, resembling the longitudinal bone growth phenotype of patients with inactivating mutations in ERα or aromatase. It is unknown whether the effects of estrogens on skeletal growth are mediated directly via ERs in growth plate cartilage. Using a mouse model with cartilage-specific inactivation of ERα, we found that during early sexual maturation, ERα in growth plate cartilage is not important for skeletal growth. In contrast, it is essential for high-dose estradiol to reduce the growth plate height in adult mice and for reduction of longitudinal bone growth in elderly mice.

ERα stimulates target gene transcription through two activation functions (AFs), AF-1 in the N-terminal and AF-2 in the ligand binding domain. Using domain-specific ER-inactivated mouse models, we demonstrated that 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 uterus but not cortical bone, suggesting that selective ER modulators stimulating ERα with minimal activation of ERα AF-1 could retain beneficial actions in cortical bone while minimizing effects on reproductive organs. We recently demonstrated that ERα amplifies the osteogenic response to mechanical loading in a ligand-independent manner involving its AF-1 but not AF-2. Thus AF-2 but not AF-1 is required for the estradiol effect in cortical bone while ERα AF-1 but not AF-2 is required for the osteogenic loading response.

Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Funding: This work was supported, however funding details are unavailable.

Volume 29

15th International & 14th European Congress of Endocrinology

European Society of Endocrinology 

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