Endocrinology systems exert an important effect on vascular function and have direct actions on blood vessels.
Estrogens provoke an increase in skin elasticity, epidermal hydration, skin thickness, reduce skin wrinkles and augment the content of
collagen and the level of vascularisation. Therefore, there is an intricate cross-talk between skin conditions and stress. In stress, β2--adrenoreceptor (β2AR) pathway,
cortisol,
epinephrine and
norepinephrine increase DNA damage and interfere with the regulation of the cell cycle, contributing to aging and
skin diseases.
Substance P is a
neuropeptide released in the skin from the peripheral nerve and is related to stress and
inflammation. SP provokes infiltration of inflammatory cells in the skin and induces a variety of
cytokines/
chemokines.
Corticotropin-releasing hormone (CRH), produced by mast cells, is a
neuropeptide also expressed in skin and responds to stress. CRH initiates diverse intracellular signaling pathways, including
cAMP, protein kinase C, and
mitogen-activated protein kinases (MAPK). Under stress, CRH,
glucocorticoids,
epinephrine and
cytokines are generated. Moreover, the release of
ACTH binds the receptor MC2-R and stimulates the generation of
glucocorticoids such as
corticosterone and
cortisol, which interact with the
transcription factors AP-1 and
NF-kB. In skin keratinocytes,
ACTH promotes the generation of pro-inflammatory
cytokines, which enhances T-cell activity.
Cortisol is immunosuppressive by inhibiting Th1 and Th2 cell response, antigen presentation, antibody and
cytokine/
chemokine production. However,
glucocorticoids are certainly helpful in Th1-mediated autoimmune disorders. On the other hand,
cytokines, such as TNF,
IL-1 and
IL-6, stimulate the generation of CRH and activate HPA axis in inflammatory states. Here, we describe for the first time a cross-talk between endocrinology and skin, including pro-inflammatory
cytokines and neurogenic inflammatory pathways.