Human Scalp Hair Follicles Are Both a Target and a Source of Prolactin, which Serves as an Autocrine and/or Paracrine Promoter of Apoptosis-Driven Hair Follicle Regression

Abstract

The prototypic pituitary hormone prolactin (PRL) exerts a wide variety of bioregulatory effects in mammals and is also found in extrapituitary sites, including murine skin. Here, we show by reverse transcriptase-polymerase chain reaction and immunohistology that, contrary to a previous report, human skin and normal human scalp hair follicles (HFs), in particular, express both PRL and PRL receptors (PRL-R) at the mRNA and protein level. PRL and PRL-R immunoreactivity can be detected in the epithelium of human anagen VI HFs, while the HF mesenchyme is negative. During the HF transformation from growth (anagen) to apoptosisdriven regression (catagen), PRL and PRL-R immunoreactivity appear up-regulated. Treatment of organ-cultured human scalp HFs with high-dose PRL (400 ng/ml) results in a significant inhibition of hair shaft elongation and premature catagen development, along with reduced proliferation and increased apoptosis of hair bulb keratinocytes (Ki-67/terminal dUTP nick-end labeling immunohistomorphometry). This shows that PRL receptors, expressed in HFs, are functional and that human skin and human scalp HFs are both direct targets and sources of PRL. Our data suggest that PRL acts as an autocrine hair growth modulator with catagenpromoting functions and that the hair growth-inhibitory effects of PRL demonstrated here may underlie the as yet ill-understood hair loss in patients with hyperprolactinemia.

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

“…2A). This finding was particularly interesting given that Prl signaling has previously been implicated in the regulation of hair growth (Craven et al 2001(Craven et al , 2006Foitzik et al 2003Foitzik et al , 2006). However, a role for Prl signaling in the regulation of bulge SC activity has not been reported.…”

“…Autocrine Prl signaling can also control mammary gland differentiation into lactogenic epithelial cells (Chen et al 2012). In the skin, Prl addition to culture human HFs can induce catagen, and Prlr-null mice display altered hair cycling in the absence of pregnancy (Craven et al 2001(Craven et al , 2006Foitzik et al 2006). Given the broad expression of Prlr in different cell types (Bole-Feysot et al 1998) and the numerous tissue changes that occur during pregnancy and lactation, tissue-specific disruption of Prl signaling will help to elucidate the likely broad role of systemic Prl in SC regulation.…”

“…Prl has been reported to signal through Akt (Acosta et al 2003;Chakravarti et al 2005;Chen et al 2012) and Map kinase (Das and Vonderhaar 1995), both of which are activated in bulge cells during the native hair cycle (Affara et al 2006;Festa et al 2011) and may act downstream from Prl. Adding further complexity to the matter are reports of local Prl expression in human skin (Foitzik et al 2006) that suggest that Prl can also signal in an autocrine or paracrine manner. Ultimately, elucidating the global molecular mechanisms of Prl signaling in the skin in both native and pregnant conditions may have relevance for other epithelial tissues that respond to this pleiotrophic hormone.…”

“…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). Prl receptors (Prlrs) are expressed within the HF in both mice and humans, and Prl can induce follicle death in cultured skin tissue from both species (Foitzik et al 2003(Foitzik et al , 2006. Exogenous Prl delays hair growth in murine skin associated with inhibition of Prl secretion during the native hair cycle (Craven et al 2006), and Prlr knockout mice exhibit precocious hair growth during native hair cycling and in skin grafts (Craven et al 2001(Craven et al , 2006, indicating a functional role for Prl signaling in the skin.…”

Biology of Human Hair: Know Your Hair to Control It

“…Prolactin is implicated in hair growth regulation in both mice and human [112][113][114]. Similarly, melatonin has been reported to promote hair growth in animals and in humans, where topical application of melatonin induced hair, probably through induction of anagen [115].…”