In many instances, whether these effects are direct or involve paracrine regulators remains debated. give rise to 1 (or few) mature cell types (1). Historically, the best characterized stem cells have been those of the hematopoietic lineage; the first review articles referenced in PubMed appeared in the 1960s. Since these pioneering reports, growing evidence for the presence of adult stem cells in several other tissues has accumulated. One of the models of choice for the study of adult stem cells in epithelial tissue is the crypt-villus system of the small intestine, thanks to the very short life cycle (4C5 d) of its epithelial cell layer that requires permanent renewal (2). Studies of this peculiar system led to the discovery that both slow/noncycling and fast-cycling intestinal stem cells coexist. The fast-cycling stem cells that express Lgr5 (leucine-rich repeat-containing G protein-coupled receptor 5) (3) are the engines of crypt self-renewal: they can generate a population of slow/nondividing daughter cells that can either differentiate into Paneth cells or, in case of damage, be used as reserve stem cells that can reacquire the ability to express Lgr5 and give rise to other differentiated intestinal cells (4, 5). In all, it seems that under physiological conditions, certain tissues like the intestine and skin can self-renew constantly via asymmetric division of stem cells. In contrast, other tissues mainly rely on multipotent progenitors for self-renewal (hematopoietic system), or around the replication of differentiated, mature cells (liver and pancreatic -cells) (6, 7). In addition to these physiological mechanisms of self-renewal, tissue injury or aggression also can activate self-renewal processes, eg, the prostate epithelium after Thevetiaflavone castration and androgen restitution (8). Thevetiaflavone The activation of these stem/progenitor cells eventually leads to tissue repair and regeneration. Thanks to their regenerating capacities, adult stem cells add potential value to the current therapeutic arsenal, as highlighted for decades by hematopoietic stem cells from bone marrow used for transplantation purposes. The more recent discoveries that adult stem cells also reside in organs long thought to be Rabbit Polyclonal to hnRNP L unable to regenerate, such as the brain or the heart, have opened new routes for developing unsuspected cell-based therapies for neurologic disorders or heart diseases (9). The manipulation of adult somatic cells into induced pluripotent stem cells offers great promise in this field as well (10). Finally, within recent years, stem cells have also emerged as potential drivers of, and hence as new targets for, cancer initiation and perhaps even more cancer recurrence. For example, chemotherapy-resistant breast cancer cells exhibit stem-like properties making them good candidates for initiating breast cancer regrowth upon escape after initial treatment (11). Whether these cells are true cancer stem cells, resulting from oncogenic transformation of stem cells, or whether they represent dedifferentiated cells resulting from the phenotypic conversion of transformed epithelial cells (eg, through epithelial-mesenchymal transition [EMT]), remains a matter of debate (12,C14), which falls beyond the scope of this minireview. The microenvironment where stem cells are localized within each tissue provides signals regulating their quiescence, self-renewal, and survival, which are essential for stem cell homeostasis. This microenvironment, called the stem cell niche, includes the stem Thevetiaflavone cells and their progeny, surrounding mesenchymal or stromal cells, extracellular matrix, and other cell types, such as endothelial and neural cells (15). In each tissue, the stem cell niche presents particular properties, which involve regulatory autocrine, paracrine, and/or endocrine signals (15). The main signaling pathways known to regulate stem cell homeostasis involve the TGF- superfamily, the Wingless-type mammary tumor virus integration site family (Wnt) pathway, and Notch signaling; however, many other factors have been described to play a role (15). In this minireview we will discuss what is known about the effects of the hormone prolactin (PRL) on adult tissue stem or progenitor cells. The PRL Axis Intracellular signaling PRL is usually a pituitary-secreted polypeptide hormone of 23 000 Da. It elicits its biological functions via a specific receptor, the PRL receptor (PRLR). As an archetype member of the cytokine receptor superfamily, the PRLR is usually a nonenzyme single-pass transmembrane receptor that requires associated kinases to propagate and translate the hormonal signal into transcriptional activation of target genes. Many recent reviews have.