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Query: UNIPROT:P01189 (beta-endorphin)
 21,003 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This paper reviews the action of hormones on the epidermal melanin unit. Slight attention is paid to the hormonal regulation of the melanophore. Melanin serves 2 main functions in the epidermis: 1) The pigment protects underlying structures from the harmful effects of sunlight; and 2) It serves to influence the color of the epidermis. 1 mechanism by which hormones can influence the amount of melanin involves changes in the activity to the enzyme tryosinase in the melanoblasts which synthesize the pigment. A second mechanism may involve changes in the activity of keratinocytes which engulf the melanin discharged from melanoblasts. Hormones can also influence the dispersion of melanin. Interstitial cell-stimulating hormone, estrogens, melanocyte-stimulating hormone and adrenocorticotrophin appear to increase epidermal melanin by enhancing the activity of tyrosinase. The action of interstitialcell-stimulating hormone (ICSH) upon melanogenesis has been studied in weaver birds. It has been shown that estrogens are capable of accelerating the synthesis of melanin, and that the action is a direct effect of the hormone itself, because the response occurs locally when the hormone is applied directly to the skin. It has been observed that skin color varies with the menstrual cycle. Such variations may result from the synergistic action of estrogens and progesterone. A similar mechanism accounts for the pigmentation of pregnancy. Studies have shown that estrogens also influence the color of feathers in certain birds. Melanocyte-stimulating hormone (MSH) has been shown to increase the melanin content of the epidermis of the guinea pig, and promotes the dispersion of melanin into the dendritic processes of the melanocyte and into adjacent keratinocytes. Adrenocorticotropic hormone (ACTH) prossesses some MSH activity, although it is much less potent than MSH itself. Presumably the hormone acts like MSH, directly on the melanocyte. These 2 hormones darken the skin in man, and 1 or both is responsible for the well known pigmentation which follows bilateral adrenalectomy when replacement therapy is inadequate. The influence of thyroxine upon epidermal melanin is complex and varies from species to species. The action of androgens on melanogenesis is both complex and ill-understood. Adrenoline and noradrenaline inhibit the action of MSH on frog skin but there is no direct evidence that these hormones influence the mammalian melanocyte. Further investigations are needed.
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PMID:The influence of hormones on melanogenesis. 1230 81

Four diarylheptanoids, (5R-1,7-bis (3,4-dihydroxyphenyl)-heptane-5-O-beta-D-glucoside (1), (5R) 1,7-bis (3,4-dihydroxyphenyl)-heptane-5-ol (2), oregonin (3), hirsutanonol (4), were isolated from the bark of Alnus hirsuta Turcz and its inhibitory effects on melanogenesis by measuring the melanin level and tyrosinase activity in B16 melanoma cell were examined. Melanin level and tyrosinase activity were reduced to 75 to 85% by addition of diarylheptanoids to incubation medium of the melanoma cell. On the other hand, melanin level and tyrosinase activity were reduced to 13 to 43% by the addition of diarylheptanoids to incubation medium of the melanoma cell treated with melanogenesis stimulator, alpha-MSH and forskolin. These melanogenesis inhibitory effects were significantly different compared with control.
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PMID:Melanogenesis inhibitory activities of diarylheptanoids from Alnus hirsuta Turcz in B16 mouse melanoma cell. 1251 Aug 43

Melanin pigments produced in human melanocytes are classified into two categories; black coloured eumelanin and reddish-yellow pheomelanin. Stimulation of melanocytes with alpha-melanocyte-stimulating hormone (alpha-MSH), one of several melanogenic factors, has been reported to enhance eumelanogenesis to a greater degree than pheomelanogenesis, which contributes to hyperpigmentation in skin. Nitric oxide (NO) and histamine are also melanogenesis-stimulating factors that are released from cells surrounding melanocytes following ultraviolet (UV) irradiation. In this study, the effects of NO and histamine on the ratio of eumelanin and pheomelanin were examined in human melanocytes, and then compared with that of alpha-MSH. The amounts of eumelanin and pheomelanin were quantified using high-performance liquid chromatography analysis after oxidation and hydrolysis of melanin. Melanogenesis was induced by the addition of alpha-MSH, NO, or histamine to melanocytes. The amount of eumelanin production significantly increased with independent stimulation by these melanogenic factors, especially histamine, while that of pheomelanin significantly increased with alpha-MSH and NO, but only slightly with histamine. As a result, the ratio of eumelanin and pheomelanin increased significantly with the addition of NO or histamine. These results suggest that NO and histamine, as in the case of alpha-MSH, may contribute to UV-induced hyperpigmentation by enhancing eumelanogenesis.
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PMID:Effects of melanogenesis-inducing nitric oxide and histamine on the production of eumelanin and pheomelanin in cultured human melanocytes. 1251 29

Frog melanophores rapidly change colour by dispersion or aggregation of melanosomes. A long-term colour change exists where melanosomes are released from melanophores and transferred to surrounding skin cells. No in vitro model for pigment transfer exists for lower vertebrates. Frog melanophores of different morphology exist both in epidermis where keratinocytes are present and in dermis where fibroblasts dominate. We have examined whether release and transfer of melanosomes can be studied in a melanophore-fibroblast co-culture, as no frog keratinocyte cell line exists. Xenopus laevis melanophores are normally cultured in conditioned medium from fibroblasts and fibroblast-derived factors may be important for melanophore morphology. Melanin was exocytosed as membrane-enclosed melanosomes in a process that was upregulated by alpha-melanocyte-stimulating hormone (alpha-MSH), and melanosomes where taken up by fibroblasts. Melanosome membrane-proteins seemed to be of importance, as the cluster-like uptake pattern of pigment granules was distinct from that of latex beads. In vivo results confirmed the ability of dermal fibroblasts to engulf melanosomes. Our results show that cultured frog melanophores can not only be used for studies of rapid colour change, but also as a model system for long-term colour changes and for studies of factors that affect pigmentation.
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PMID:Studies of pigment transfer between Xenopus laevis melanophores and fibroblasts in vitro and in vivo. 1652 29

Epidermal melanin reduces some effects of UV radiation, the major cause of skin cancer. To examine whether induced melanin can provide protection from sunburn injury, 65 subjects completed a trial with the potent synthetic melanotropin, [Nle4-D-Phe7]-alpha-melanocyte-stimulating hormone ([Nle4-D-Phe7]-alpha-MSH) delivered by subcutaneous injection into the abdomen at 0.16 mg/kg for three 10-day cycles over 3 months. Melanin density, measured by reflectance spectroscopy, increased significantly in all [Nle4-D-Phe7]-alpha-MSH-treated subjects. The highest increases were in volunteers with lowest baseline skin melanin levels. In subjects with low minimal erythemal dose (MED) skin type, melanin increased by an average of 41% (from 2.55 to 3.59, P < 0.0001 vs placebo) over eight separate skin sites compared with only 12% (from 4.18 to 4.70, P < 0.0001 vs placebo) in subjects with a high-MED skin type. Epidermal sunburn cells resulting from exposure to 3 MED of UV radiation were reduced by more than 50% after [Nle4-D-Phe7]-alpha-MSH treatment in the volunteers with low baseline MED. Thymine dimer formation was also shown to be reduced by 59% (P = 0.002) in the epidermal basal layer. This study has shown for the first time the potential ability of a synthetic hormone that augments melanin production to provide photoprotection to people who normally burn in direct sunlight.
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PMID:[Nle4-D-Phe7]-alpha-melanocyte-stimulating hormone significantly increased pigmentation and decreased UV damage in fair-skinned Caucasian volunteers. 1676 47

Melanin synthesized by epidermal melanocytes protects the skin against UVR-induced DNA damage and skin cancer. Exposure to UVR increases the synthesis of the photoprotective eumelanin on activation of MC1R, a melanoma susceptibility gene. We studied the expression of MC1R under UVR and alpha-MSH stimulation in skin of different ethnic origins and in melanocytes of various pigmentary levels. This study identifies and characterizes a novel MC1R isoform (MC1R350) generated by alternative splicing of the classically known MC1R (MC1R317). We demonstrate that the melanin content of melanocytes shows a significant positive correlation with MC1R317 levels but correlates inversely with the amount of MC1R350, suggesting that this latter isoform could act as a negative regulator of melanin synthesis. We confirmed that hypothesis by showing that while MC1R317 signaling significantly increases the expression of MITF and tyrosinase, two key factors in the melanin synthesis pathway, MC1R350 dramatically hampers their expression. In the skin, we show that UVR does not increase MC1R350 expression but does significantly increase MC1R317. Taken together, our results strongly suggest that MC1R350 acts as a negative regulator of skin pigmentation and demonstrate for the first time that MC1R isoform-specific expression is closely related to skin pigmentation and photoprotection.
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PMID:Regulation of constitutive and UVR-induced skin pigmentation by melanocortin 1 receptor isoforms. 1687 22

Malignant melanoma affects approximately 40,000 new patients each year in the United States and an estimated 100,000 people worldwide. There is no satisfactory treatment for patients with metastatic melanoma that have an estimated 5-year survival of 6%. The potential of radioimmunotherapy (RIT) for the treatment of metastatic melanoma was recognized very early by RIT pioneers when murine melanoma was successfully treated by DeNardo, and later when Larson reported a shrinkage of tumor in a patient with metastatic melanoma treated with 131I-labeled Fab' fragments of a mAb against high-molecular-weight melanoma-associated antigen. Despite successes in the 1980s, RIT of melanoma did not develop into a clinical modality. The reasons for this are complex. In recent years, RIT has made an impression, as evidenced by the recent approval of Zevalin and Bexxar (anti-CD20 mAbs labeled with 90Y and 131I, respectively). Now there is a "window of opportunity" for RIT to become an effective therapy for metastatic melanoma. Surface antigen GD3 has been evaluated in patients as a potential target for melanoma RIT; pretargeting the administration of antibodies and intralesional administration of an antibody labeled with potent alpha-emitter 213-Bismuth have shown promise in clinical studies. Melanin, the pigment that gives melanoma its name, has emerged as a novel antigen for delivery of radioactivity to the tumors by antimelanin antibody. Simultaneously, radiolabeled metal-cyclized alpha-MSH peptide analogs and melanin-binding peptides are being developed as targeting molecules for melanoma. Overall, we are hopeful that targeted radionuclide therapy of metastatic melanoma will become a reality within the next few years.
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PMID:Renaissance of targeting molecules for melanoma. 1725 69

Arbutin has been used as a whitening agent in cosmetic products. Melanin, the major pigment that gives color to skin, may be over-produced with sun exposure or in conditions such as melasma or hyperpigmentary diseases. Tyrosinase is a key enzyme that catalyzes melanin synthesis in melanocytes; therefore, inhibitors of the tyrosinase enzyme could be used for cosmetic skin whitening. A recent study has reported that arbutin decreases melanin biosynthesis through the inhibition of tyrosinase activity. However, this inhibitory mechanism of arbutin was not sufficiently demonstrated in skin tissue models. We found that arbutin both inhibits melanin production in B16 cells induced with alpha-MSH and decreases tyrosinase activity in a cell-free system. Furthermore, the hyperpigmentation effects of alpha-MSH were abrogated by the addition of arbutin to brownish guinea pig and human skin tissues. These results suggest that arbutin may be a useful agent for skin whitening.
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PMID:Inhibitory effects of arbutin on melanin biosynthesis of alpha-melanocyte stimulating hormone-induced hyperpigmentation in cultured brownish guinea pig skin tissues. 1938 80

Melanin-based traits involved in animal communication have been traditionally viewed as occurring under strict genetic control. However, it is generally accepted that both genetic and environmental factors influence melanin production. Medical studies suggest that, among environmental factors influencing melanization, oxidative stress could play a relevant role. On the other hand, genetic control would be exerted by the melanocortin system, and particularly by the alpha-melanocyte-stimulating hormone (alpha-MSH), which triggers the production of eumelanins (black pigments). To determine how the melanocortin system and an exogenous source of oxidative stress interact in the expression of melanin-based plumage, developing red-legged partridges (Alectoris rufa) were manipulated. Some partridges were injected with alpha-MSH, while other birds received a pro-oxidant molecule (diquat) in drinking water. Controls and birds receiving both treatments were also studied. Both alpha-MSH- and diquat-treated individuals presented larger eumelanin-based traits than controls, but alpha-MSH+diquat-treated birds showed the largest traits, suggesting that oxidative stress and melanocortins promote additive but independent effects. Diquat also induced a decline in the level of a key intracellular antioxidant (glutathione), which is associated with high expression of eumelanin-based signals in other bird species. Some scenarios for the evolution of melanin-based traits in relation to oxidative stress are proposed.
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PMID:The expression of melanin-based plumage is separately modulated by exogenous oxidative stress and a melanocortin. 1952 Aug 1

Melanin granule (melanosome) dispersion within Xenopus laevis melanophores is evoked either by light or alpha-MSH. We have previously demonstrated that the initial biochemical steps of light and alpha-MSH signaling are distinct, since the increase in cAMP observed in response to alpha-MSH was not seen after light exposure. cAMP concentrations in response to alpha-MSH were significantly lower in cells pre-exposed to light as compared to the levels in dark-adapted melanophores. Here we demonstrate the presence of an adenylyl cyclase (AC) in the Xenopus melanophore, similar to the mammalian type IX which is inhibited by Ca(2+)-calmodulin-activated phosphatase. This finding supports the hypothesis that the cyclase could be negatively modulated by a light-promoted Ca(2+) increase. In fact, the activity of calcineurin PP2B phosphatase was increased by light, which could result in AC IX inhibition, thus decreasing the response to alpha-MSH. St-Ht31, a disrupting agent of protein kinase A (PKA)-anchoring kinase A protein (AKAP) complex totally blocked the melanosome dispersing response to alpha-MSH, but did not impair the photo-response in Xenopus melanophores. Sequence comparison of a melanophore AKAP partial clone with GenBank sequences showed that the anchoring protein was a gravin-like adaptor previously sequenced from Xenopus non-pigmentary tissues. Co-immunoprecipitation of Xenopus AKAP and the catalytic subunit of PKA demonstrated that PKA is associated with AKAP and it is released in the presence of alpha-MSH. We conclude that in X. laevis melanophores, AKAP12 (gravin-like) contains a site for binding the inactive PKA thus compartmentalizing PKA signaling and also possesses binding sites for PKC. Light diminishes alpha-MSH-induced increase of cAMP by increasing calcineurin (PP2B) activity, which in turn inhibits adenylyl cyclase type IX, and/or by activating PKC, which phosphorylates the gravin-like molecule, thus destabilizing its binding to the cell membrane.
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PMID:Light modulates the melanophore response to alpha-MSH in Xenopus laevis: an analysis of the signal transduction crosstalk mechanisms involved. 1953 25


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