Stem Cells with Neurogenic Potential and Steroid Hormones

Pluripotent and multipotent stem cells with differentiation potential to neural phenotypes have been described and characterized in the last decades. Embryonic stem cells, as well as neural stem cells from developing and adult nervous system, can differentiate into different types of neurons, astrocytes or oligodendrocytes. Although the initially identified actions of estradiol, progesterone and testoterone are related to sexual reproductive functions, recent evidence shows that these steroid hormones modulate development, physiology and survival of nerve cells. Furthermore, neurosteroids can be synthesized in the developing and adult nervous system. A description of the molecular modulatory actions of sex steroid hormones on the Central Nervous System is presented. The main focus of this review is to summarize the described effects of steroid hormones (progesterone, allopregnanolone, dehydroepiandrosterone, estradiol and androgens) on cell parameters relevant to stem cells, both in vitro and in vivo. The overall conclusion is that steroid hormones influence stem cell behavior by several mechanisms, namely regulation of gene expression by binding to their cognate receptors, activation of intracellular pathways involving kinases or intracellular calcium signaling, and modulation of receptors for neurotransmitters; in some instances, these hormones can substitute or modulate the action of growth factors, and also directly influence self-renewal, proliferation, differentiation or cell death of neurogenic stem cells.