Neuroendocrinology of the skin

Abstract

More than ten years ago a comprehensive model of the skin acting as neuro-endocrine organ has been proposed. 1 Although the concept is still evolving, 1-7 it relies on the skin capacity to communicate with the central system and to regulate global homeostasis through local production and/or systemic release of classical hormones, neuropeptides, neurotransmitters and biological regulators (Fig. 1). 1 The skin is not only a classical source of vitamin D 8 but also a place of synthesis and metabolism of several neuropeptides including elements of hypothalamic-pituitary-adrenal (HPA), 1,9-12 and hypothalamic-pituitary-thyroid (HPT), [13][14][15][16] axes. Skin cells also possess fully functional serotonin-and melatoninergic systems [17][18][19][20][21][22] and express steroidogenic activity. 1,12 The presence of several neuropeptides and other biologically active compounds in the skin is due to both their local synthesis and active transport from blood or release form nerves endings or migrating immune cells. [1][2][3]23 The newly synthesized the concept on the skin neuro-endocrine has been formulated ten years ago, and recent advances in the field further strengthened this role. thus, skin forms a bidirectional platform for a signal exchange with other peripheral organs, endocrine and immune systems or brain to enable rapid and selective responses to the environment in order to maintain local and systemic homeostasis. In this context, it is not surprising that the function of the skin is tightly regulated by systemic neuro-endocrine system. Skin cells and skin appendages not only respond to neuropeptides, steroids and other regulatory signals, but also actively synthesis variety of hormones. the stress responses within the skin are tightly regulated by locally synthesized factors and their receptor expression. there is growing evidence for alternative splicing playing an important role in stress signaling. Deregulation of the skin neuro-endocrine signaling can lead or/and be a marker of variety of skin diseases. the major problem in this area relates to their detailed mechanisms of crosstalk between skin and brain and between the local and global endocrine as well as immune systems.

Introduction

“…Importantly, all of those isoforms except newly discovered CRF1β/d and CRF1i were found in human skin (Mikhailova et al, 2007, Slominski et al, 2007a, Zmijewski and Slominski, 2010, Zmijewski and Slominski, 2011). Interestingly, only one isoform of CRF1 (CRF1β) contains all 14 exons, while the main functional isoform, CRF1α, has an exon 6 spliced out.…”

“…Other CRF1 isoforms might be divided into three groups: soluble receptors (CRF1e and CRFh), receptors with defects in the extracellular domain (ECD) (isoform c) and receptors with impaired 7TM domain (CRF1d, f, g and also CRF1β/d fits to this group). The detailed exonal organization of CRF1 isoforms is shown in Figure 11 and was discussed elsewhere (Hillhouse and Grammatopoulos, 2006a, Slominski et al, 2006c, Zmijewski and Slominski, 2010b, Zmijewski and Slominski, 2011). It has to be noted that alterative splicing of CRF1 also results in a frame shift which introduces premature stop codon to the sequence of CR1e, f, g and h. Alternative splicing of CRF1 receptor mRNA seems to be a conserved phenomenon in evolution because CRF1 isoforms were also identified in rat (Hillhouse and Grammatopoulos, 2006a, Slominski et al, 2001), mouse (Pisarchik and Slominski, 2001) and hamster (Pisarchik and Slominski, 2002).…”

“…A fourth type of the CRF signaling modulation is represented by the soluble CRF1h isoform (Slominski et al, 2006c, Zmijewski and Slominski, 2011). The intracellular retention and co-localization within ER of CRF1h was shown in cells overexpressing this isoform (Zmijewski and Slominski, 2009a, Zmijewski and Slominski, 2009b).…”

“…The strategic location of the skin as the barrier between the environment and internal milieu determines its critical function in the preservation of body homeostasis, and ultimately organism survival (Slominski, 2005, Slominski and Wortsman, 2000, Slominski et al, 2000c, Zmijewski and Slominski, 2011). It also exposes skin to numerous pathological agents, processes, and events.…”

Linalool prevents oxidative stress activated protein kinases in single UVB-exposed human skin cells

“…As skin is continuously exposed to numerous biotic and abiotic factors, it has been evolved with protective mechanisms in order to cope up local and global aggressive environment [2]. For example, skin possesses strong antioxidant systems which maintain redox homeostasis against oxidative threat in the cellular milieu [3].…”