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.

Autocrine/paracrine roles of extrapituitary growth hormone and prolactin in health and disease: An overview

“…Pit-1, which is lacking exon 1, also activates the extrapituitary prolactin gene in mouse spermatids and spermatocytes (Maeda et al, 2012). Extrapituitary prolactin was also considered to be dopamine-independent, as dopamine did not inhibit prolactin production in the decidua (Golander et al, 1979), nor amniotic fluid ( Lehtovirta and Ranta, 1981) or in human skin (Langan et al, 2013). However, human adipocytes express functional dopamine receptors and dopamine stimulation inhibits prolactin gene expression in these sites (Borcherding et al, 2011).…”

“…Estrogen similarly stimulates prolactin production in the rat brain (Torner et al, 1999), although it does not stimulate prolactin release from glandular breast tissue not breast adipose tissue (Zinger et al, 2003). In contrast with pituitary prolactin, substance P, TNF (tumor necrosis factor) α and interferon (IFN) γ have also been found to be novel modulators of prolactin expression in human skin (substance P and TNF α as inhibitors and IFN γ as a stimulator) (Langan et al, 2013).…”

Psychological Stress-Derived Prolactin Modulates Occludin Expression in Vaginal Epithelial Cells to Compromise Barrier Function

“…Supporting results are published. Langan et al report that skin cells also produce PRL [23]. Epithelial barrier dysfunction is associated with a large number of diseases.…”

Role of organic osmolytes in water homoeostasis in skin

“…Surprisingly, osmoregulatory hormones also appear to have receptors in human skin. For example, mineralocorticoid receptors (MR) and prolactin receptors and their ligands are found in human epidermis, sebaceous glands and hair follicles although their downstream effects are not clear. In the epidermis, the expression of ENaC , a key regulator of Na + homoeostasis, might be a potential downstream effector of prolactin and the aldosterone–MR‐signalling cascade, thereby helping in some way to regulate ionic gradients in the epidermis and thereby water balance.…”