Human haematopoietic stem/progenitor cells express several functional sex hormone receptors

Abstract

Evidence has accumulated that murine haematopoietic stem/progenitor cells (HSPCs) share several markers with the germline, a connection supported by recent reports that pituitary and gonadal sex hormones (SexHs) regulate development of murine HSPCs. It has also been reported that human HSPCs, like their murine counterparts, respond to certain SexHs (e.g. androgens). However, to better address the effects of SexHs, particularly pituitary SexHs, on human haematopoiesis, we tested for expression of receptors for pituitary SexHs, including follicle‐stimulating hormone (FSH), luteinizing hormone (LH), and prolactin (PRL), as well as the receptors for gonadal SexHs, including progesterone, oestrogens, and androgen, on HSPCs purified from human umbilical cord blood (UCB) and peripheral blood (PB). We then tested the functionality of these receptors in ex vivo signal transduction studies and in vitro clonogenic assays. In parallel, we tested the effect of SexHs on human mesenchymal stromal cells (MSCs). Finally, based on our observation that at least some of the UCB‐derived, CD45− very small embryonic‐like stem cells (VSELs) become specified into CD45+ HSPCs, we also evaluated the expression of pituitary and gonadal SexH receptors on these cells. We report for the first time that human HSPCs and VSELs, like their murine counterparts, express pituitary and gonadal SexH receptors at the mRNA and protein levels. Most importantly, SexH if added to suboptimal doses of haematopoietic cytokines and growth factors enhance clonogenic growth of human HSPCs as well as directly stimulate proliferation of MSCs.

Pituitary sex hormones enhance the pro-metastatic potential of human lung cancer cells by downregulating the intracellular expression of heme oxygenase-1

“…Namely, since pituitary SexH receptors are expressed by cells from the germ lineage beginning at the very early stages of embryogenesis (35,36), and, as demonstrated in this study, lung cancer cells also express pituitary SexH rec eptors, there may be a developmental link between these cells, as suggested at the beginning of this section. Interestingly, 150 years ago Virchow (37) and Cohnheim (38) proposed that some malignancies develop from dormant embryonic or germ cells residing in adult tissues.…”

“…One can speculate that these or closely related cells could theoretically be the source of some tumors. In support of this possibility, VSELs express several SexH receptors as well as genes involved in primordial germ cell development (35,36,39,41). This working hypothesis, however, requires more experimental evidence.…”

Androgen/androgen receptor axis maintains and promotes cancer cell stemness through direct activation of Nanog transcription in hepatocellular carcinoma

“…Androgen receptor (AR) is a 110 kDa transcription factor, which plays a role in regulating the expression of target genes after being activated by androgen [3]. The axis had been demonstrated to be involved in many kinds of cancer-related processes, like facilitating cancer cell growth and modulating cell cycle through TGFβ1 or β-catenin pathways, respectively [4–7], and participating in cellular growth and proliferation associated with FOXA1/2 [8–10]. However, the underneath mechanisms of the axis in the hepatocarcinogenesis gender disparity are still largely unknown.…”

Why are hematopoietic stem cells so ‘sexy’? on a search for developmental explanation

“…Other similarities include i) the similar expression of functional receptors for erythropoietin 60 and vitamin D3, 63 ii) the hematopoietic specification of both types of cells, 16,18,36 and iii) the expression of several receptors for sex hormones (highlighted in this review). 64,65 …”