Human megakaryocytes and platelets contain the estrogen receptor beta and androgen receptor (AR): testosterone regulates AR expression

Gender differences in vascular thromboses are well known, and there is evid ence that platelets may be involved in these differences and that sex hormo nes affect platelet function. We characterized the expression of the estrog en receptor alpha (ER alpha), estrogen receptor beta (ER beta), progesteron e receptor (PR), and androgen receptor (AR) in the megakaryocyte lineage. M egakaryocytes generated ex vivo from normal human CD34(+) stem cells contai ned RNA for ER beta and AR, which increased with cell differentiation. Plat elets and human erythroleukemia (HEL) cells also contained ER beta and AR t ranscripts. No ER or or PR messenger RNA or protein was detected in the meg akaryocyte lineage. Immunofluorescence microscopy showed that ER beta prote in was present in glycoprotein (GP) IIb(+) megakaryocytes and the HEL megak aryocytic cell line in a predominantly cytoplasmic location. AR showed a cy toplasmic and nuclear distribution in GPIIb(+) and GPIIb(-) cells derived f rom CD34(+) cells and in HEL cells. Western immunoblotting confirmed the pr esence of ER beta and AR in platelets. Megakaryocyte and HEL AR expression was up-regulated by 1, 5, and 10 nmol/L testosterone, but down-regulated by 100 nmol/L testosterone, These findings indicate a regulated ability of me gakaryocytes to respond to testosterone and suggest a potential mechanism t hrough which sex hormones may mediate gender differences in platelet functi on and thrombotic diseases. (Blood, 2000;95:2289-2296) (C) 2000 by The Amer ican Society of Hematology.