Role of melatonin receptors in hair biology

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Jacob
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Role of melatonin receptors in hair biology

Post by Jacob » Tue Feb 08, 2005 5:52 am

As posted by Kofi at alt.baldspot:

Exp Dermatol. 2005 Feb;14(2):157.


Expression and functional relevance of melatonin receptors in hair
follicle biology.


Kobayashi H, Paus R.


Department of Dermatology, University of Hamburg, 20246 Hamburg, Germany.


The prototypic pineal hormone, melatonin reputedly exerts many
functional effects on mammalian skin and/or its isolated cell
populations in culture (e.g., melanogenesis inhibition, melanocyte
growth inhibition, regulation of seasonal changes in the pelage), and is
recognized as a potent free radical scavenger. In mammals, two types of
high-affinity membrane melatonin receptors, MT1 and MT2 have been
identified, which inhibit adenylate cyclase activity to decrease the
intracellular level of cAMP. Low-affinity membrane receptor MT3/QR2 have
also been identified, though the mechanism has not been cleared yet.
Melatonin is also a natural ligand of nuclear transcription factor
ROR(alpha and beta), which is suggested to regulate cell cycle
negatively via target gene such as p21(WAF/CIP1). Due to its lipophilic
structure, melatonin also enters through both the plasma and nuclear
membrane, and acts as a potent free radical scavenger to protect
macromolecules, in particular DNA. Melatonin demonstrates differential -
and often still confusing seemingly contradictory- effects on cell
activity in many different systems, which may be explained by this
multitude of signaling pathways that are modulated by melatonin
bioactivity. Recently, cultured epidermal and follicular melanocytes,
keratinocytes, and fibroblasts, have also been found to display the
enzymatic activity of arylalkylamine N-acetyltransferase and
hydroxyindole -O- methyltransferase for melatonin synthesis. However,
little is known about the cutaneous expression and regulation of
melatonin and its receptors in situ, and the functional role of
melatonin in normal skin and hair follicle biology is still obscure. In
order to study whether murine hair follicles in situ are indeed direct
peripheral melatonin targets, the follicular expression of MT1, MT2
and/or RORalpha are investigated. Immunohistochemistry revealed that
C57BL/6 mouse hair follicle keratinocytes in situ show prominent
MT1-like immunoreactivity (IR), which changed substantially in a hair
cycle-dependent manner. RORalpha-like IR was also detected in murine
hair follicles, and also displayed hair cycle dependence. RT-PCR of MT1
and MT2, and real time PCR for MT1, MT2 and RORalpha on C57BL/6 mice
skin cDNA revealed that all three genes are transcribed in normal mouse
skin, and demonstrated that their expression/transcription is hair
cycle-dependent. In conclusion, normal murine hair follicles are indeed
a prominent, direct target for melatonin bioregulation, through MT1, MT2
and RORalpha melatonin receptors and that at least some of these
regulators are functionally active in situ. The observed hair cycle
dependence of melatonin receptor expression suggests a role of melatonin
in hair cycle control.


PMID: 15679607

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