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Physiological Reviews, Vol. 80, No. 3, July 2000, pp. 979-1020
Copyright ©2000 by the American Physiological Society
Department of Pathology, Loyola University Medical Center, Maywood; Department of Medicine, Southern Illinois University, Springfield, Illinois; Department of Dermatology, Ludwig Boltzmann Institute of Cell Biology and Immunobiology of the Skin, University of Munster, Munster; Department of Dermatology, University Hospital Eppendorf, University of Hamburg, Hamburg, Germany; and Department of Medicine and Biochemistry, McGill University and Royal Victoria Hospital, Montreal, Quebec, Canada
Slominski, Andrzej,
Jacobo Wortsman,
Thomas Luger,
Ralf Paus, and
Samuel Solomon.
Corticotropin Releasing Hormone and Proopiomelanocortin
Involvement in the Cutaneous Response to Stress. Physiol. Rev. 80: 979-1020, 2000.
The skin is a known target
organ for the proopiomelanocortin (POMC)-derived neuropeptides
-melanocyte stimulating hormone (-MSH), 
-endorphin, and ACTH
and also a source of these peptides. Skin expression levels of the POMC
gene and POMC/corticotropin releasing hormone (CRH) peptides are not
static but are determined by such factors as the physiological changes
associated with hair cycle (highest in anagen phase), ultraviolet
radiation (UVR) exposure, immune cytokine release, or the presence of
cutaneous pathology. Among the cytokines, the proinflammatory
interleukin-1 produces important upregulation of cutaneous levels of
POMC mRNA, POMC peptides, and MSH receptors; UVR also stimulates
expression of all the components of the CRH/POMC system including
expression of the corresponding receptors. Molecular characterization
of the cutaneous POMC gene shows mRNA forms similar to those found in
the pituitary, which are expressed together with shorter variants. The
receptors for POMC peptides expressed in the skin are functional and
include MC1, MC5 and µ-opiate, although most predominant are those of
the MC1 class recognizing MSH and ACTH. Receptors for CRH are also
present in the skin. Because expression of, for example, the MC1
receptor is stimulated in a similar dose-dependent manner by UVR,
cytokines, MSH peptides or melanin precursors, actions of the ligand
peptides represent a stochastic (predictable) nonspecific response to
environmental/endogenous stresses. The powerful effects of POMC
peptides and probably CRH on the skin pigmentary, immune, and adnexal
systems are consistent with stress-neutralizing activity addressed
at maintaining skin integrity to restrict disruptions of internal
homeostasis. Hence, cutaneous expression of the CRH/POMC system is
highly organized, encoding mediators and receptors similar to the
hypothalamic-pituitary-adrenal (HPA) axis. This CRH/POMC skin system
appears to generate a function analogous to the HPA axis, that in the
skin is expressed as a highly localized response which neutralizes
noxious stimuli and attendant immune reactions.
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