From:
Sukie Crandall
Date: 2008-08-20 20:11:15 UTC
Subject: [ferrethealth] melatonin studies which may be of interest?
To: fhl <ferrethealth@yahoogroups.com>
I don't know (yet) if or how much furthering there has
been on aspects of how melatonin regrows fur that do
NOT involve changes at the adrenal level. (Both skin
and adrenals ultimately have their own responses
so it is important to not think that the skin response
is due to the adrenal response.)
According to
<http://scienceblogs.com/clock/2008/08/to_equine_things_there_is_a_se.php?u=
tm_source=3Dsbhomepage&utm_medium=3Dlink&utm_content=3Dchannellink
>
> Seasonal hair growth and pigmentation cycles have been studied=20
> extensively in sheep, goats, mink, arctic fox, and mice, and it is=20
> clear that they are responsive to photoperiod and melatonin levels.=20
> As Coturnix has described previously in his blog, melatonin is a=20
> multifunctional lipophilic molecule, primarily produced by the=20
> pineal gland in response to noradrenergic stimulation from=20
> sympathetic neurons. Numerous brain areas have high levels of=20
> melatonin receptors, but cells in other organs, including the skin,=20
> are also responsive to melatonin. The transcription levels of genes=20
> encoding melatonin receptors appear to be correlated with the hair=20
> cycle phases of telogen (resting) and anagen (growth). Hair follicle=20
> activity and hair shaft elongation are very responsive to melatonin,=20
> with both "overcoat" and "undercoat" fur affected; these effects of=20
> melatonin on hair growth have been demonstrated in sheep, goats,=20
> mink, ferrets, dogs, and red deer (Fischer et al., 2008).
Sooooo
Going to PubMed to see what may be new and possibly apply to ferrets I=20
find:
BEGIN QUOTED ABSTRACTS
Exp Dermatol. 2008 Jul 17. [Epub ahead of print]
> Melatonin as a major skin protectant: from free radical scavenging=20
> to DNA damage repair.
>
> Fischer TW, Slominski A, Zmijewski MA, Reiter RJ, Paus R.
> Department of Dermatology, University Hospital Schleswig-Holstein,=20
> University of L=FCbeck, L=FCbeck, Germany.
>
> Melatonin, one of the evolutionarily most ancient, highly conserved=20
> and most pleiotropic hormones still operative in man, couples=20
> complex tissue functions to defined changes in the environment.=20
> Showing photoperiod-associated changes in its activity levels in=20
> mammals, melatonin regulates, chronobiological and reproductive=20
> systems, coat phenotype and mammary gland functions. However, this=20
> chief secretory product of the pineal gland is now recognized to=20
> also exert numerous additional functions which range from free=20
> radical scavenging and DNA repair via immunomodulation, body weight=20
> control and the promotion of wound healing to the coupling of=20
> environmental cues to circadian clock gene expression and the=20
> modulation of secondary endocrine signalling (e.g. prolactin=20
> release, oestrogen receptor-mediated signalling). Some of these=20
> activities are mediated by high-affinity membrane (MT1, MT2) or=20
> specific cytosolic (MT3/NQO2) and nuclear hormone receptors=20
> (RORalpha), while others reflect receptor-independent antioxidant=20
> activities of melatonin. Recently, it was shown that mammalian=20
> (including human) skin and hair follicles are not only melatonin=20
> targets, but also sites of extrapineal melatonin synthesis.=20
> Therefore, we provide here an update of the relevant cutaneous=20
> effects and mechanisms of melatonin, portray melatonin as a major=20
> skin protectant and sketch how its multi-facetted functions may=20
> impact on skin biology and pathology. This is illustrated by=20
> focussing on recent findings on the role of melatonin in=20
> photodermatology and hair follicle biology. After listing a number=20
> of key open questions, we conclude by defining particularly=20
> important, clinically relevant perspectives for how melatonin may=20
> become therapeutically exploitable in cutaneous medicine.
> PMID: 18643846
J Pineal Res. 2008 Jan;44(1):1-15.
Melatonin and the hair follicle.
Fischer TW, Slominski A, Tobin DJ, Paus R.
Department of Dermatology, University Hospital Schleswig-Holstein,=20
University of L=FCbeck, L=FCbeck, Germany.
Melatonin, the chief secretory product of the pineal gland, has long=20
been known to modulate hair growth, pigmentation and/or molting in=20
many species, presumably as a key neuroendocrine regulator that=20
couples coat phenotype and function to photoperiod-dependent=20
environmental and reproductive changes. However, the detailed effects=20
and mechanisms of this surprisingly pleiotropic indole on the hair=20
follicle (HF) regarding growth control and pigmentation have not yet=20
been completely understood. While unspecific melatonin binding sites=20
have long been identified (e.g., in goat and mouse HFs), specific=20
melatonin membrane MT2 receptor transcripts and both protein and mRNA=20
expression for a specific nuclear melatonin binding site [retinoid-
related orphan receptor alpha (RORalpha)] have only recently been=20
identified in murine HFs. MT1, known to be expressed in human skin=20
cells, is not transcribed in mouse skin. After initial enzymologic=20
data from hamster skin related to potential intracutaneous melatonin=20
synthesis, it has recently been demonstrated that murine and human=20
skin, namely human scalp HFs in anagen, are important sites of=20
extrapineal melatonin synthesis. Moreover, HF melatonin production is=20
enhanced by catecholamines (as it classically occurs in the pineal=20
gland). Melatonin may also functionally play a role in hair-cycle=20
control, as it down-regulates both apoptosis and estrogen receptor-
alpha expression, and modulates MT2 and RORalpha expression in murine=20
skin in a hair-cycle-dependent manner. Because of melatonin's=20
additional potency as a free radical scavenger and DNA repair inducer,=20
the metabolically and proliferatively highly active anagen hair bulb=20
may also exploit melatonin synthesis in loco as a self-cytoprotective=20
strategy.
PMID: 18078443
Exp Dermatol. 2008 Jul;17(7):625.
Towards new aspects of melatonin research in dermato-endocrinology.
Fischer TW, Naumann V, Bodo E, Paus R.
Department of Dermatology, Allergology and Venerology, University=20
Hospital Schleswig-Holstein, University of L=FCbeck, L=FCbeck, Germany.
Based on extensive investigation of melatonin in human cell models=20
(keratinocytes, fibroblasts), a great variety of melatonin actions,=20
mechanisms, intracellularly localized synthesis and metabolism as well=20
as receptor expression has been unravelled, identifying melatonin as a=20
key player in cutaneous biology and dermato-endocrinology. Melatonin=20
was reported to act directly protective as a radical scavenger in many=20
conditions of skin-related stress (ultraviolet radiation, ionizing=20
radiation, thermal injury, ulcer formation, skin flap necrosis) and to=20
modulate cell growth via membrane (MT1, MT2), cytosolic (MT3/NQO2) and=20
nuclear receptors (RORalpha). Membrane and nuclear melatonin receptor=20
expression is hair cycle dependent in murine hair follicles, whereas=20
estradiol receptor (ERalpha) expression is down-regulated by=20
melatonin. Furthermore, the modulation of secondary endocrine=20
signalling (e.g. prolactin release, estrogen receptor-mediated=20
signalling) in the skin is mediated by melatonin. Melatonin levels of=20
magnitudes higher than in the plasma have been detected in human=20
keratinocytes and murine and human hair follicles, whereby=20
noradrenalin, the classical stimulator of melatonin synthesis,=20
increased melatonin production in hair follicles. Additionally, a=20
melatoninergic antioxidative system (MAS) of the skin has been=20
identified with UV-enhanced formation of melatonin metabolites, 2-OH-
melatonin and AFMK, the latter being a strong antioxidant itself.=20
Alternatively, melatonin indirectly protects cells by up-regulating=20
gene expression and activity of non-melatonin autonomous protective=20
systems, the intracellular antioxidative enzyme network which is=20
composed of Mn-SOD, Cu-Zn-SOD, CAT and GPx. To further drive melatonin=20
research towards the human organism level, two human organ culture=20
models have been choosen or newly established i) the human hair organ=20
culture model and ii) the human full thickness skin model,=20
respectively. Two crucial stressors of human skin/hair biology are=20
used to investigate their morphology and functional effect expression=20
in these models: ultraviolet radiation and chemotherapy-induced=20
cytotoxicity. Standardized stress conditions in both models serve to=20
investigate differential expression of stress levels, their time-
dependent dynamics and effect quality. Finally, reduction of UV-
damaged keratinocytes (sun-burn cells) by melatonin in the full-skin=20
organ model and anti-apoptotic effects in chemotherapy-induced hair=20
follicle damage have been observed.
PMID: 18558998
[The NZ studies below]
J Histochem Cytochem. 1996 Apr;44(4):377-87.
Transforming growth factor-alpha immunoreactivity during induced hair=20
follicle growth cycles in sheep and ferrets.
Nixon AJ, Broad L, Saywell DP, Pearson AJ.
AgResearch, Ruakura Research Centre, Hamilton, New Zealand.
Transforming growth factor-alpha (TGF-alpha) has been associated with=20
cell proliferation of keratinocytes and implicated in hair growth. We=20
therefore examined changes in the immunocytochemical localization of=20
TGF-alpha and cell proliferation markers in the skin of two unrelated=20
species in which hair cycles could be induced, to elucidate the role=20
of this growth factor in the control of fiber growth. Skin was=20
collected from melatonin-treated ferrets (Mustela putorius furo),=20
untreated Romney sheep (Ovis aries), and New Zealand Wiltshire sheep=20
in which interruption of wool growth had been photoperiodically=20
induced. Immunostaining patterns were very similar in ferrets and=20
sheep. TGF-alpha immunoreactivity was observed in epithelial tissues=20
of the skin but was not co-localized with cell proliferation markers.=20
In anagen follicles, specific staining was most intense in the=20
innermost cells of the outer root sheath and cortical cells in the=20
keratogenous zone but was absent from inner root sheath or dermal=20
papilla. TGF-alpha immunostaining diminished during catagen, although=20
faint staining was retained in all epithelial cells. In telogen and=20
early proanagen follicles, staining remained faint or was restricted=20
to cells on the margin of the brush end and follicle neck.=20
Immunoreactivity in the outer root sheath was reestablished in late=20
proanagen. Sebaceous glands and epidermis were stained intensely=20
throughout the hair cycle. TGF-alpha-immunoreactive components of skin=20
extracts, analyzed by Western blotting, showed mobility corresponding=20
to approximately 32 KD, but not to the size of the fully cleaved=20
peptide. These results are consistent with an epithelial autocrine or=20
juxtacrine, but not a mitogenic, function of TGF-alpha.
PMID: 8601697
can be found here:
http://www.jhc.org/cgi/reprint/44/4/377
and
J Exp Zool. 1995 Aug 15;272(6):435-45.Links
Seasonal fiber growth cycles of ferrets (Mustela putorius furo) and=20
long-term effects of melatonin treatment.
Nixon AJ, Ashby MG, Saywell DP, Pearson AJ.
Ruakura Research Centre, Hamilton, New Zealand.
Pelage cycles of ferrets are poorly documented, although it is clear=20
that their timing is sensitive to daylength, mediated by pineal=20
melatonin. Hair follicles were monitored histologically in ferrets=20
from 3 to 19 months of age in order to describe naturally occurring=20
changes in follicle growth status and follicle number over three=20
successive cycles of fur growth. Melatonin was administered to some of=20
these animals in late summer to determine the long-term effects of=20
perturbation of hormonal control. Circulating melatonin was elevated=20
for approximately 50 days by 8-mg continuous release implants. Treated=20
animals grew both their first winter coat, and subsequent summer coats=20
18 days in advance of untreated controls, but this effect did not=20
extend to the second winter coat. Reimplantation the following year=20
induced an advancement of the autumn follicle growth as in the 1st=20
year. Autumn fiber growth occurred at similar times in untreated males=20
and females, and response to melatonin did not differ between sexes.=20
Hair follicle regression and shedding during the natural spring molt=20
was also contemporaneous in males and females, but fiber regrowth=20
occurred 4-6 weeks later in males as compared with females, suggesting=20
that reproduction-related factors affect fiber growth initiation, and=20
that fiber growth and shedding are physiologically distinct processes.=20
Melatonin implants in autumn also affected reproduction in the spring,=20
advancing oestrus by 3-4 weeks. These results show that interference=20
with photoperiodic and hormonal control mechanisms in ferrets can=20
affect pelage and reproductive cycles for up to 10 months.
PMID: 7673877
END QUOTED ABSTRACTS
So, now I wonder if including melatonin in the medical treatment=20
approach (along with either Lupron or deslorelin) might also help=20
protect the skin, and if it might be useful for some other skin=20
problems in ferrets as part of the therapy.
BTW, in some ways the early neutering simulates menopause, and there=20
is some new work indicating that melatonin which is highest AT THE=20
RIGHT TIMES may help reduce some of the unpleasant effects some women=20
have with menopause, but if it peaks too late then some of the effects=20
can be worse, so be careful -- if you are giving oral melatonin -- to=20
always give it at the right time. More info on that:
http://www.miamiferret.org/fhc/melatonin.htm
Sukie (not a vet)
Recommended ferret health links:
http://pets.groups.yahoo.com/group/ferrethealth/
http://ferrethealth.org/archive/
http://www.afip.org/ferrets/index.html
http://www.miamiferret.org/fhc/
http://www.ferretcongress.org/
http://www.trifl.org/index.shtml
http://homepage.mac.com/sukie/sukiesferretlinks.html
[Non-text portions of this message have been removed]
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