Deletion of estrogen receptors reveals a regulatory role for estrogen receptors-beta in bone remodeling in females but not in males
| Autor: | Dominique Minet, Roland Baron, S Dupont, A Krust, P Clement-Lacroix, Martine Gaillard-Kelly, Michèle Resche-Rigon, Natalie A. Sims |
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| Rok vydání: | 2002 |
| Předmět: |
Male
medicine.medical_specialty Histology Bone density Physiology medicine.drug_class Endocrinology Diabetes and Metabolism Estrogen receptor Biology Bone resorption Bone remodeling Mice Bone Density Internal medicine medicine Animals Estrogen Receptor beta Testosterone Estrogen receptor beta Bone growth Mice Knockout Sex Characteristics Bone Development Estradiol Estrogen Receptor alpha Endocrinology Receptors Estrogen Estrogen Female Bone Remodeling Estrogen receptor alpha hormones hormone substitutes and hormone antagonists |
| Zdroj: | Bone. 30(1) |
| ISSN: | 8756-3282 |
| Popis: | To determine the contributions of estrogen receptor (ER)alpha and ERbeta in bone growth and remodeling in male and female mice, we generated and analyzed full knockouts for each receptor, and a double ER knockout. Although suppression of the ligand to the ERs (i.e., estradiol) after menopause or gonadectomy in females led to a catastrophic increase in bone turnover and concomitant bone loss, deletion of one or both ERs failed to show such an effect. Complete deletion of ERalpha led to a decrease, not an increase, in bone turnover and an increase, not a decrease, in trabecular bone volume in both male and female animals. Deletion of ERbeta led to different responses in males, where bone was unaffected, and in females, where bone resorption was decreased and trabecular bone volume increased. In contrast, deletion of both ERs led to a profound decrease in trabecular bone volume in females, which was associated with a decrease, not an increase, in bone turnover. Finally, deletion of ERalpha, but not ERbeta, led to major changes in circulating levels of estradiol and/or testosterone, indirectly affecting bone remodeling and bone mass. Thus, only ERalpha was shown to regulate bone remodeling in males, whereas in females both receptor subtypes influenced this process and could, at least under basal knockout conditions, compensate for each other. |
| Databáze: | OpenAIRE |
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