Prolactin and Its Receptor Are Expressed in Murine Hair Follicle Epithelium, Show Hair Cycle-Dependent Expression, and Induce Catagen

Abstract

Here, we provide the first study of prolactin (PRL) and prolactin receptor (PRLR) expression during the nonseasonal murine hair cycle, which is, in contrast to sheep, comparable with the human scalp and report that both PRL and PRLR are stringently restricted to the hair follicle epithelium and are strongly hair cycle-dependent. In addition we show that PRL exerts functional effects on anagen hair follicles in murine skin organ culture by down-regulation of proliferation in follicular keratinocytes. In telogen follicles, PRL-like immunoreactivity was detected in outer root sheath (ORS) keratinocytes. During early anagen (III to IV), the developing inner root sheath (IRS) and the surrounding ORS were positive for PRL. In later anagen stages, PRL could be detected in the proximal IRS and the inner layer of the ORS. The regressing (catagen) follicle showed a strong expression of PRL in the proximal ORS. In early anagen, PRLR immunoreactivity occurred in the distal part of the ORS around the developing IRS, and subsequently to a restricted area of the more distal ORS during later anagen stages and during early catagen. The dermal papilla (DP) stayed negative for both PRL and PRLR throughout the cycle. Telogen follicles showed only a very weak PRLR staining of ORS keratinocytes. The long-form PRLR transcript was shown by real-time polymerase chain reaction to be transiently down-regulated during early anagen, whereas PRL transcripts were up-regulated during mid anagen. Addition of PRL (400 ng/ml) to anagen hair follicles in murine skin organ culture for 72 hours induced premature catagen development in vitro along with a decline in the number of proliferating hair bulb keratinocytes. These data support the intriguing concept that PRL is generated locally in the hair follicle epithelium and acts directly in an autocrine or paracrine manner to modulate the hair cycle. Hair follicles are unusual in that they undergo lifelong cycles of growth and regression. Active hair growth (anagen) is accompanied by hair shaft elongation, melanogenesis, and by massive keratinocyte proliferation, whereas hair follicle regression (catagen) is characterized by terminal differentiation and apoptosis, resulting in the resting stage (telogen) and in hair shaft shedding (exogen). The molecular mechanisms that are responsible for this tightly controlled process are still not clear, but in the last decade a large, yet limited number of growth factors, cytokines, neuropeptides, neurotransmitters, and hormones have been shown to play important regulatory roles.1-3 A particularly intriguing issue in this context is the search for the set of locally generated hormones and neurotrophines that are involved in that growth control 4,5 beyond the well-recognized effects of locally metabolized steroid hormones.

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

“…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. Furthermore, by identifying CN/Nfatc1 and Stat5 signaling as essential components of the pathway that regulates and responds to Prlr in follicular SCs, respectively, our data increase our understanding of the complex hormonal mechanisms that regulate mammalian hair growth.…”

“…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.…”

“…While previous work has implicated Prl signaling in the control of hair growth during the native hair cycle (Craven et al 2001(Craven et al , 2006Foitzik et al 2003), several questions remain regarding the global mechanisms of Prl signaling in the skin. Although Prlr is up-regulated in bulge cells relative to HG cells (Fig.…”

“…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.…”

Short Communication A novel single-nucleotide polymorphism in the 5' upstream region of the prolactin receptor gene is associated with fiber traits in Liaoning cashmere goats

“…Prolactin (PRL) has been implicated as the principal endocrine regulator in pelage replacement in a diverse array of mammals (Dicks et al, 1994;Pearson et al, 1996;Thompson Jr. et al, 1997), and all biological functions associated with PRL are mediated by its specific receptor prolactin receptor (PRLR), which is a single-pass membrane-bound protein that belongs to the cytokine receptor family (Kelly et al, 2001;Foitzik et al, 2003). Furthermore, PRLR has been shown to be expressed in the wool follicles of sheep (Choy et al, 1997), and result in hair cycle perturbations and slightly longer and coarser hair in mice (Craven et al, 2001).…”