title: Therapeutic effect of androgen therapy in a mouse model of aplastic anemia produced by short telomeres.
abstract: Aplastic anemia is a rare but life-threatening disorder characterized by cytopenia in at least two of the three blood lineages. A frequent feature of patients with aplastic anemia is that they have shorter telomeres than those of age-matched controls. Testosterone has been used for over half a century in the treatment of aplastic anemia. However, although remissions are frequent following hormone therapy, the molecular mechanism underlying the response to treatment has remained unknown. Here we explored the possibility that the recently described regulation of telomerase activity by sex hormones may be the mechanism responsible. To this end, we used a mouse model of aplastic anemia induced by short telomeres in the bone marrow compartment. We found that testosterone therapy results in telomerase up-regulation, improved blood counts, and a significant extension of life-span of these mice. Importantly, longitudinal follow-up studies revealed longer telomeres in peripheral blood in mice subjected to hormone treatment. Our results demonstrate that testosterone-mediated telomerase activation can attenuate or reverse aplastic anemia disease progression associated with the presence of short telomeres.
authors.affiliation: Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Centre (CNIO), Melchor Fernández Almagro 3, Madrid, Spain.
authors.forename: Christian
authors.initials: C
authors.lastname: Bär
authors.affiliation: Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Centre (CNIO), Melchor Fernández Almagro 3, Madrid, Spain.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Huber
authors.affiliation: Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Centre (CNIO), Melchor Fernández Almagro 3, Madrid, Spain Department of Hematology, Oncology and Stem Cell Transplantation, Medical Faculty, RWTH Aachen University Germany.
authors.forename: Fabian
authors.initials: F
authors.lastname: Beier
authors.affiliation: Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Centre (CNIO), Melchor Fernández Almagro 3, Madrid, Spain mblasco@cnio.es.
authors.forename: Maria A
authors.initials: MA
authors.lastname: Blasco
mesh_terms: D000728:Androgens / Q000008:administration & dosage / Q000494:pharmacology*; D000741:Anemia, Aplastic / Q000097:blood / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D004958:Estradiol / Q000008:administration & dosage / Q000494:pharmacology; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D012333:RNA, Messenger / Q000235:genetics; D019098:Telomerase / Q000235:genetics / Q000378:metabolism; D059506:Telomere Shortening; D013739:Testosterone / Q000008:administration & dosage / Q000494:pharmacology
chemical_list: D000728:Androgens; D012333:RNA, Messenger; D013739:Testosterone; D004958:Estradiol; D019098:Telomerase; C509187:Tert protein, mouse