title: Tumour necrosis factor alpha, interferon gamma and substance P are novel modulators of extrapituitary prolactin expression in human skin.
abstract: Human scalp skin and hair follicles (HFs) are extra-pituitary sources of prolactin (PRL). However, the intracutaneous regulation of PRL remains poorly understood. Therefore we investigated whether well-recognized regulators of pituitary PRL expression, which also impact on human skin physiology and pathology, regulate expression of PRL and its receptor (PRLR) in situ. This was studied in serum-free organ cultures of microdissected human scalp HFs and skin, i.e. excluding pituitary, neural and vascular inputs. Prolactin expression was confirmed at the gene and protein level in human truncal skin, where its expression significantly increased (p = 0.049) during organ culture. There was, however, no evidence of PRL secretion into the culture medium as measured by ELISA. PRL immunoreactivity (IR) in female human epidermis was decreased by substance P (p = 0.009), while neither the classical pituitary PRL inhibitor, dopamine, nor corticotropin-releasing hormone significantly modulated PRL IR in HFs or skin respectively. Interferon (IFN) γ increased PRL IR in the epithelium of human HFs (p = 0.044) while tumour necrosis factor (TNF) α decreased both PRL and PRLR IR. This study identifies substance P, TNFα and IFNγ as novel modulators of PRL and PRLR expression in human skin, and suggests that intracutaneous PRL expression is not under dopaminergic control. Given the importance of PRL in human hair growth regulation and its possible role in the pathogenesis of several common skin diseases, targeting intracutaneous PRL production via these newly identified regulatory pathways may point towards novel therapeutic options for inflammatory dermatoses.
authors.affiliation: Dermatology Research Centre, Manchester Academic Health Science Centre, and Institute of Inflammation and Repair, University of Manchester, Manchester, United Kingdom.
authors.forename: Ewan A
authors.initials: EA
authors.lastname: Langan
authors.forename: Silvia
authors.initials: S
authors.lastname: Vidali
authors.forename: Natascha
authors.initials: N
authors.lastname: Pigat
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Funk
authors.forename: Erika
authors.initials: E
authors.lastname: Lisztes
authors.forename: Tamás
authors.initials: T
authors.lastname: Bíró
authors.forename: Vincent
authors.initials: V
authors.lastname: Goffin
authors.forename: Christopher E M
authors.initials: CE
authors.lastname: Griffiths
authors.forename: Ralf
authors.initials: R
authors.lastname: Paus
mesh_terms: D000328:Adult; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology; D004298:Dopamine / Q000494:pharmacology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D018859:Hair Follicle / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D008875:Middle Aged; D009924:Organ Culture Techniques; D011388:Prolactin / Q000235:genetics / Q000378:metabolism; D011981:Receptors, Prolactin / Q000235:genetics / Q000378:metabolism; D012535:Scalp / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D012867:Skin / Q000187:drug effects* / Q000378:metabolism; D013373:Substance P / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D011981:Receptors, Prolactin; D014409:Tumor Necrosis Factor-alpha; D013373:Substance P; D007371:Interferon-gamma; D011388:Prolactin; D003346:Corticotropin-Releasing Hormone; D004298:Dopamine