Prolactin and the skin: A dermatological perspective on an ancient pleiotropic peptide hormone

The polypeptide hormone prolactin (PRL) is best known as the pituitary modulator of lactation and reproduction. However, based on the almost ubiquitous distribution of PRL receptors (PRLR) and an ever-growing list of extrapituitary PRL-expressing tissues, a vast range of PRL actions "beyond the mammary horizon" has now been documented or claimed. For example, PRL modulates hair growth in domestic animals with seasonal hair growth changes ("PRL-pelage axis"). Given that the mammary gland is an epidermal derivative, it is not surprising that the pilosebaceous unit, another epidermal derivative, has also surfaced as a prominent, PRLR-expressing, nonclassical PRL target organ. Moreover, the fact that murine and human hair follicles even synthesize PRL strongly invites one to explore fully the dermatological dimensions of this multifunctional, cytokine-like neuroendocrine bioregulator, which remain insufficiently charted. After describing the relevant essentials of general PRL/PRLR biology, we summarize clinical observations that provide insights into how PRL may impact on the skin, and define important research frontiers and controversies in the quest to better characterize the complex role of PRL in human skin biology and pathology. Focusing on psoriasis, alopecia, and stress-related dermatoses, we then discuss the possible role of PRL/PRLR in cutaneous pathology, and identify potential therapeutic targets for the management of these skin disorders. We close by delineating major open questions at this emerging frontier of basic and clinical cutaneous neuroendocrinology, and argue that systematic exploration of the "PRL-skin connection" will fertilize the development of previously unreported neuroendocrinological strategies for managing selected skin disorders.