Direct and Indirect Effects of Androgens on Survival of Hematopoietic Progenitor Cells In Vitro

Abstract

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, 5β-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-γ). 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.

Comparison in haematological and biochemical changes in normal, acute and chronically castrated West African Dwarf goats

“…34 In the available literature, there is evidence that testosterone enhances the absorption of iron, its incorporation into red blood cells and hemoglobin synthesis. 35 Testosterone-induced increase in hematocrit and hemoglobin is associated with elevated erythropoietin levels, but this is also accompanied by other mechanisms, such as reduced hepcidin (the ironregulatory peptide) and ferritin. 36 Anemia is partially associated with reduced levels of circulating androgens.…”

Serum testosterone levels and excessive erythrocytosis during the process of adaptation to high altitudes

“…67 However, survival-enhancing or growth-stimulatory effects of androgens on haematopoietic progenitor cells are minimal and mostly restricted to mature erythroid progenitors in experiments using human purified (CD34 1 ) erythroid progenitors in vitro. 68 Moreover, no AR expression has been observed in erythroid cells. 69 Instead, androgens act through AR to modulate the mRNA expression of several haematopoietic growth factors in bone marrow stromal cells.…”

Decanoato de nandrolona no hemograma e nas células mononucleares da medula óssea de ratos Wistar hígidos

“…Pode-se observar que, ratificando os achados do sangue circulante, não houve diferença estatística entre os grupos, o que demonstra que as doses utilizadas de DN, mesmo em doses supraclínicas, não foram capazes de afetar o número de CM da MO em ratos saudáveis. Esses achados concordam com KIM et al (2005), que não encontram estimulação de dois outros andrógenos sobre as CT e os progenitores sanguíneos in vitro.…”

“…O estudo com células-tronco mononucleares permite o desenvolvimento e/ou aprimoramento de terapias celulares, validando a chamada medicina regenerativa ou de reparo (HUANG et al, 2004;GALLIAN, 2005;CUMANO & GODIN, 2007). Trabalhos sobre a viabilidade das CT são necessários, já que há dúvidas se os andrógenos afetam a sobrevivência desse tipo de célula (KIM et al, 2005). Além disso, a identificação de marcadores moleculares de superfície dos fenótipos das CT hematopoéticas, como o CD34+, é importante no transplante clínico e na terapia gênica (ITO et al, 2000).…”