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Blood, 10 September 2009, Vol. 114, No. 11, pp. 2236-2243. Prepublished online as a Blood First Edition Paper on June 26, 2009; DOI 10.1182/blood-2008-09-178871. This Article Full Text (PDF) All Versions of this Article: blood-2008-09-178871v1 114/11/2236    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Google Scholar Articles by Calado, R. T. Articles by Young, N. S. PubMed PubMed Citation Articles by Calado, R. T. Articles by Young, N. S. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted September 11, 2008 Accepted June 18, 2009 Sex hormones, acting on the TERT gene, increase telomerase activity in human primary hematopoietic cells Rodrigo T. Calado*, William T. Yewdell, Keisha L. Wilkerson, Joshua A. Regal, Sachiko Kajigaya, Constantine A. Stratakis, and Neal S. Young Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, United States Section on Endocrinology and Genetics, Program on Developmental Endocrinology and Genetics, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, United States * Corresponding author; email: calador{at}nhlbi.nih.gov. Androgens have been used in the treatment of bone marrow failure syndromes without a clear understanding of their mechanism of action. Blood counts of patients with dyskeratosis congenita or aplastic anemia with mutations in telomerase genes can improve with androgen therapy. Here we observed that exposure in vitro of normal peripheral blood lymphocytes and human bone marrow-derived CD34+ cells to androgens increased telomerase activity, coincident with higher TERT mRNA levels. Cells from patients who were heterozygous for telomerase mutations had low baseline telomerase activity, which was restored to normal levels by exposure to androgens. Estradiol had an effect similar to androgens on TERT gene expression and telomerase enzymatic activity. Tamoxifen, an estrogen receptor antagonist, abolished the effects of both estradiol and androgens on telomerase function, and letrozole, an aromatase inhibitor, blocked androgen effects on telomerase activity. Conversely, flutamide, an androgen receptor antagonist, did not affect androgen stimulation of telomerase. Down-regulation by siRNA of estrogen receptor- (ER) but not ER inhibited estrogen-stimulated telomerase function. Our results provide a mechanism for androgen therapy in bone marrow failure: androgens appear to regulate telomerase expression and activity mainly by aromatization and through ER. These findings have potential implications for the choice of current androgenic compounds and the development of future agents for clinical use. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: TERTrific hormones promote hematopoiesis Laura S. Haneline Blood 2009 114: 2207-2208. [Full Text] [PDF] This article has been cited by other articles: Androgens, Telomerase, and Aplastic Anemia Journal Watch Oncology and Hematology, October 20, 2009; 2009(1020): 4 - 4. [Full Text] L. S. Haneline TERTrific hormones promote hematopoiesis Blood, September 10, 2009; 114(11): 2207 - 2208. [Full Text] [PDF]

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