Prolactin and the Skin: A Dermatological Perspective on an Ancient Pleiotropic Peptide Hormone

Abstract

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.

Calcineurin/Nfatc1 signaling links skin stem cell quiescence to hormonal signaling during pregnancy and lactation

“…Outside of pregnancy, patients with hyperprolactinemia exhibit increased serum Prl levels and also report increased hair loss (Orfanos and Hertel 1988;Foitzik et al 2009;Lutz 2012). While Prl may promote catagen to increase hair shedding during both pregnancy and hyperprolactinemia (Foitzik et al 2003(Foitzik et al , 2006, our finding that Prl stalls HF SC activation may serve as an additional explanation for Prl-induced hair loss in humans.…”

“…Prolactin (Prl) is highly elevated during pregnancy and lactation, and several lines of evidence have implicated a function for Prl signaling in the control of hair growth outside of pregnancy. In humans, patients with elevated serum Prl levels (or hyperprolactinemia) can experience hair loss (Orfanos and Hertel 1988;Foitzik et al 2009;Lutz 2012). Additionally, Prl has been implicated in the regulation of epidermal appendage growth in several avian and mammalian species (Duncan and Goldman 1984;Pearson et al 1996;Dawson and Sharp 1998;Nixon et al 2002;Dawson et al 2009).…”

New concepts in prolactin biology

“…non-pathological) conditions remains very limited. For example, local PRL was proposed to play a role in i) mammopoiesis, based on experiments using PRL-deficient mice (Naylor et al 2003), ii) nociception, based on experiments using rat trigeminal sensory neurons (Diogenes et al 2006), or iii) dermatological bioregulation, based on experiments using organ-cultured human hair follicles (Foitzik et al 2009, Ramot et al 2010. Even if these examples are not aimed at being exhaustive, the paucity of knowledge of local PRL contrasts with the pleiotropic actions usually linked to the endocrine hormone (Bole-Feysot et al 1998).…”

Genetic and Hormonal Determinations in a Pair of Identical Twins with Early Onset Psoriasis Vulgaris: Case Report and a Brief Review of the Literature

“…Sexual hormones and PRL have been mentioned in the pathogenesis of psoriasis, due to their effect on keratinocyte proliferation and to the fact that the disease is thought to be an autoimmune disorder, influenced by psycho-emotional stress (15).…”