An overview and selective analysis

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 D8 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),13-16 axes. Skin cells also possess fully functional serotoninand melatoninergic systems17-22 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.1-3,23 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. Neuroendocrinology of the skin An overview and selective analysis