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Journal of Korean Medical Science ; : 409-416, 2005.
Artículo en Inglés | WPRIM | ID: wpr-53835

RESUMEN

Androgens remain a common treatment for certain type of anemia, based upon its myelostimulating effects; however, it has not been established whether androgens affect apoptosis of hematopoietic progenitor cells (HPCs). We investigated the effects of the androgens, such as testosterone, 5beta-dihydrotestosterone (5-DHT), and oxymetholone, on apoptosis of normal hematopoietic progenitor cells in vitro. Androgens did not rescue normal bone marrow (BM) CD34+ cells and colony-forming cells (CFCs), other than mature erythroid CFCs, from apoptosis induced by serum- and growth factor deprivation. Oxymetholone did not affect growth factor-mediated survival of normal CD34+ cells or its inhibition by interferon-gamma (IFN-gamma). In a standard methylcellulose clonogenic assay, low concentrations of oxymetholone and 5-DHT stimulated the clonal growth of colony-forming unit (CFU)-erythroid, but did not affect growth of CFU-granulocyte/macrophage or burst-forming unit-erythroid. Oxymetholone and 5-DHT stimulated the production of stem cell factor in normal bone marrow stromal cells (BMSCs) via transcriptional regulation. In agreement with this, oxymetholone-treated BMSCs better supported the survival of HPCs. These data indicate that survival-enhancing or growth-stimulatory effects of androgens on hematopoietic progenitor cells are minimal and mostly restricted to mature erythroid progenitors, and its myelostimulating effects could be attributed, at least in part, to the stimulation of production of hematopoietic growth factors in BMSCs.


Asunto(s)
Humanos , Andrógenos/farmacología , Antígenos CD34/análisis , Apoptosis/efectos de los fármacos , Northern Blotting , Western Blotting , Células de la Médula Ósea/citología , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Quimiocinas CXC/genética , Ensayo de Unidades Formadoras de Colonias , Citocinas/genética , Dihidrotestosterona/farmacología , Relación Dosis-Respuesta a Droga , Citometría de Flujo , Expresión Génica/efectos de los fármacos , Células Madre Hematopoyéticas/citología , Oximetolona/farmacología , ARN Mensajero/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Testosterona/farmacología , Factores de Tiempo
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