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

Abstract

Gender differences in vascular thromboses are well known, and there is evidence that platelets may be involved in these differences and that sex hormones affect platelet function. We characterized the expression of the estrogen receptor  (ER ), estrogen receptor β (ER β), progesterone receptor (PR), and androgen receptor (AR) in the megakaryocyte lineage. Megakaryocytes generated ex vivo from normal human CD34+ stem cells contained RNA for ER β and AR, which increased with cell differentiation. Platelets and human erythroleukemia (HEL) cells also contained ER β and AR transcripts. No ER  or PR messenger RNA or protein was detected in the megakaryocyte lineage. Immunofluorescence microscopy showed that ER β protein was present in glycoprotein (GP) IIb+ megakaryocytes and the HEL megakaryocytic cell line in a predominantly cytoplasmic location. AR showed a cytoplasmic and nuclear distribution in GPIIb+ and GPIIb− cells derived from CD34+ cells and in HEL cells. Western immunoblotting confirmed the presence of ER β 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 megakaryocytes to respond to testosterone and suggest a potential mechanism through which sex hormones may mediate gender differences in platelet function and thrombotic diseases.

Androgens stimulate endothelial progenitor cells through an androgen receptor‐mediated pathway

“…This result is concordant with the presence of AR in several cell types of human bone marrow, 23,24 as well as its expression in CD34-positive cells. 25 Moreover, it is also known that mature endothelial cells express AR, 26,27 and we have shown by immunohistochemistry that the receptor is present in the EPCs as well.…”

Effects of hormone replacement therapy on blood platelets

“…So there may be a direct effect of combined HRT on platelet function in vivo . Indeed functional oestrogen receptors are present in megakaryocytes and in blood platelets, as shown in vitro [26,27]. To our knowledge no progestagen receptors have been found in blood platelets or their precursors.…”

Role of raloxifene on platelet metabolism and plasma lipids

“…Oestrogens can modulate changes non-genomically (by affecting Ca 2+ flux, lipid metabolism, etc.) [22] and genomically seeing that oestrogen receptors have been cloned from megakaryocytes and platelets [23] .…”