Sex steroids and stem cell function

Abstract

Gender dimorphisms exist in the pathogenesis of a variety of cardiovascular, cardiopulmonary, neurodegenerative, and endocrine disorders. Estrogens exert immense influence on myocardial remodeling following ischemic insult, partially through paracrine growth hormone production by bone marrow mesenchymal stem cells (MSCs) and endothelial progenitor cells. Estrogens also facilitate the mobilization of endothelial progenitor cells to the ischemic myocardium and enhance neovascularization at the ischemic border zone. Moreover, estrogens limit pathological myocardial remodeling through the inhibitory effects on the proliferation of the cardiac fibroblasts. Androgens also may stimulate endothelial progenitor cell migration from the bone marrow, yet the larger role of androgens in disease pathogenesis is not well characterized. The beneficial effects of sex steroids include alteration of lipid metabolism in preadipocytes, modulation of bone metabolism and skeletal maturation, and prevention of osteoporosis through their effects on osteogenic precursors. In an example of sex steroid-specific effects, neural stem cells exhibit enhanced proliferation in response to estrogens, whereas androgens mediate inhibitory effects on their proliferation. Although stem cells can offer significant therapeutic benefits in various cardiovascular, neurodegenerative, endocrine disorders, and disorders of bone metabolism, a greater understanding of sex hormones on diverse stem cell populations is required to improve their ultimate clinical efficacy. In this review, we focus on the effects of estrogen and testosterone on various stem and progenitor cell types, and their relevant intracellular mechanisms.

Figure 1

Effects of estrogen on various stem cells and progenitor cells. ESC (embryonic stem cell); EPC (endothelial progenitor cell); MSC (mesenchymal stem cell); HSC (hematopoietic stem cell); CF (cardiac fibroblast); BMP (bone matrix protein); RUNX2/ CBFA1 (runt-related transcription factor 2/core-binding factor alpha).

Figure 2

Effects of androgens on various stem cells and progenitor cells. ESC (embryonic stem cell); EPC (endothelial progenitor cell); HSC (hematopoietic stem cell); NSC (neural stem cell); OPC (osteogenic progenitor cell).