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

To continue our studies on the cutaneous expression of a proopiomelanocortin/corticotropin-releasing hormone system, we investigated whether this is accompanied by adrenal-type enzymatic activity. Immortalized cultured human keratinocytes were incubated with radiolabeled corticosteroids. Analysis by thin-layer chromatography showed rapid transformation of both progesterone and deoxycorticosterone; one of the progesterone metabolites migrated at the same rate as deoxycorticosterone. Gas chromatography/mass spectrometry further identified as major species of deoxycorticosterone metabolites 3beta,6alpha,21-trihydroxy-5alpha-pregnan-20-one, 3alpha,6alpha,21-trihydroxy-5alpha-pregnan-20-one, and 3alpha5alpha- and 3beta5alpha-tetrahydrodeoxycorticosterone. Minor metabolites were 3alpha,21-dihydroxy-5-pregnen-20- one (3alphaDelta5-21-OHpregnenolone), 3beta,21-dihydroxy-5-pregnen-20-one (3betaDelta5-21-OHpregnenolone), 3alpha,21-dihydroxy-4-pregnen-20-one (3alphaDelta4-21-OHpregnenolone), 6-hydroxy-dihydrodeoxycorticosterone, and two 5-dihydrodeoxycorticosterone species. Thus, in addition to sex steroids keratinocytes also actively metabolize corticosteroids along similar enzymatic pathways. The surprising detection of 3alphaDelta5-21-OHpregnenolone and 3 betaDelta5-21-OHpregnenolone, indicating Delta4-ketosteroids to Delta5-hydroxysteroids conversion, provides strong evidence for the occurrence, at least in human keratinocytes, of isomerase activity that allows the reaction to proceed in reverse of its usual direction. As skin expresses 3alpha/beta-hydroxysteroid dehydrogenase/Delta5-Delta4 isomerases, cutaneous reactions catalyzed by these enzymes must be reversible. In conclusion, besides elements of the corticotropin-releasing hormone/proopiomelanocortin system human keratinocytes show high levels of corticosteroid metabolizing activity. Moreover, the wide array of steroid products generated from a single substrate indicates serial progressive conversion involving 5alpha-reductase, 6alpha-hydroxylase, 3alpha/beta-hydroxysteroid dehydrogenase, and reverse Delta4minus signDelta5 isomerase enzymes. As distinct from the adrenal cortex, production of A, B, Aldo, 18OHdeoxycorticosterone, or F in keratinocytes was absent or below limits of detectability.
J Invest Dermatol 2002 Feb
PMID:Gas chromatography/mass spectrometry characterization of corticosteroid metabolism in human immortalized keratinocytes. 1184 49

In ultraviolet-induced tanning, the protein levels of various gene products critical for pigmentation (including tyrosinase and tyrosinase-related protein-1) are increased in response to ultraviolet B irradiation, but changes in mRNA levels of these factors have not been investigated in vivo. We have established an in situ hybridization technique to investigate mRNA levels of pro-opiomelanocortin, tyrosinase, tyrosinase-related protein-1, dopachrome tautomerase, P-protein, Pmel-17/gp100, and microphthalmia-associated transcription factor, and have analyzed the changes in mRNA levels in the ultraviolet B-exposed skin in vivo. The right or left forearm of each volunteer was irradiated with ultraviolet B, and skin biopsies were obtained at 2 and 5 d postirradiation. mRNA level of pro- opiomelanocortin was increased 2 d after ultraviolet B irradiation, and returned to a near-basal level after 5 d, whereas the mRNA levels of tyrosinase, tyrosinase-related protein-1, dopachrome tautomerase, P-protein, and Pmel-17/gp100 showed some or no increase at 2 d, but were significantly increased 5 d after ultraviolet B irradiation. Microphthalmia-associated transcription factor mRNA was slightly increased on days 2 and 5 after ultraviolet B irradiation. Our results suggest that the mechanism of the tanning response of human skin may involve the transcriptional regulation of certain pigmentary genes, and that pro-opiomelanocortin-derived melanocortins such as alpha-melanocyte-stimulating hormone and adrenocorticotropic hormone may play a part in regulating these genes in vivo.
J Invest Dermatol 2002 Jan
PMID:Increase of pro-opiomelanocortin mRNA prior to tyrosinase, tyrosinase-related protein 1, dopachrome tautomerase, Pmel-17/gp100, and P-protein mRNA in human skin after ultraviolet B irradiation. 1185 78

Many lines of evidence indicate that the activity of sebaceous glands can be modulated by neuropeptides. Direct evidence in man, however, is still missing. We show that SZ95 sebocytes, an immortalized human sebaceous gland cell line, express receptors for alpha-melanocyte-stimulating hormone. Reverse transcription polymerase chain reaction with primers against the five melanocortin receptors and immunofluorescence studies using an antibody directed against a peptide corresponding to the amino acids 2-18 of the human melanocortin-1 receptor disclosed specific transcripts and immunoreactivity for melanocortin-1 receptor in these cells. Melanocortin-1 receptor expression was confirmed in sebocytes of normal human skin by immunohistochemistry. In contrast, no immunostaining for the melanocortin-5 receptor could be detected in sebocytes in situ, in accordance with the lack of specific transcripts for this melanocortin receptor in SZ95 sebocytes. As cytokines play an important role in the recruitment of inflammatory cells in acne and related disorders and alpha-melanocyte-stimulating hormone exerts immunomodulatory effects in many other cell types, we investigated the effect of alpha-melanocyte-stimulating hormone on interleukin-8 secretion by SZ95 sebocytes. Treatment with interleukin-1beta resulted in a marked increase in interleukin-8 release that was partially blocked by coincubation with alpha-melanocyte-stimulating hormone in a dose-dependent manner. Taken together, we show here that the melanocortin-1 receptor is expressed in vitro and in situ in human sebocytes. By modulating interleukin-8 secretion, alpha-melanocyte-stimulating hormone may act as a modulator of inflammatory responses in the pilosebaceous unit.
J Invest Dermatol 2002 Mar
PMID:Evidence for expression of melanocortin-1 receptor in human sebocytes in vitro and in situ. 1187 95

Melanocortin receptors (MC-Rs) are G-protein coupled receptors that mediate pleiotropic actions of melanocyte-stimulating hormones and adrenocorticotropin. There is increasing evidence that one of the five so far identified melanocortin receptors, i.e. melanocortin-1 receptor (MC-1R), has a more ubiquitous distribution in the skin than originally expected. In the present study, the expression of MC-1R in normal skin glands and hair follicles, various malformations and neoplasms with adnexal differentiation is described. Using an anti-MC-1R antibody directed against the amino acids 2-18 of the human MC-1R, specimens of normal healthy skin (n = 10) as well as hamartomas, cysts, hyperplasias, and benign or malignant neoplasms with eccrine, apocrine, sebaceous gland, and hair follicle differentiation (n = 98) were immunostained. MC-1R expression was widely preserved in various adnexal malformations and neoplasms as compared with normal skin and did not show major differences with regard to maturation of the neoplasms. The majority of adnexal epithelia showed an intracytoplasmically granular staining and, to a lesser extent, an intercellular staining pattern. Immunoelectron microscopical investigations revealed expression of MC-1R both along the cell surface and intracytoplasmically within tubular endosomes, the latter suggesting internalisation of the receptor. In conclusion, preserved MC-1R expression in adnexal epithelia suggests a functional role of proopiomelanocortin (POMC) in various malformations and neoplasms of the skin.
Exp Dermatol 2002 Feb
PMID:Expression of melanocortin-1 receptor in normal, malformed and neoplastic skin glands and hair follicles. 1195 27

The coding region of the hamster corticotropin releasing factor receptor type 1 was sequenced. Hamster gene appeared to be similar to mouse, rat, and human sequences with 95%, 94%, and 91% homology, respectively. Protein substitutions were generally found in the corticotropin releasing factor-binding domain. Thus, this domain can be more prone to mutations leading to changes in amino acid sequence. Hamster pituitary, eye, spleen, heart, skin, and four melanoma lines differentially expressed nine corticotropin releasing factor-R1 isoforms. These included the corticotropin releasing factor-R1alpha and corticotropin releasing factor-R1d homologs of human isoforms as well as e, f, h, j, k, m, and n isoforms. Corticotropin releasing factor-R1e mRNA had deletion of exons 3 and 4, CRF-R1j of exon 5, CRF-R1f of exon 11, CRF-R1k of exon 10, CRF-R1m of exons 11 and 12, and CRF-R1n of exons 10, 11, and 12. Corticotropin releasing factor-R1h had an insertion of a cryptic exon between exons 4 and 5. Reading frames of isoforms e, f, j, k, m, and h contained frameshifts, expected to produce truncated proteins. Corticotropin releasing factor-R1n isoform preserved the reading frame, but the transmembrane domains 6, 7, and one-third of the fifth were deleted. The AbC1 hamster melanoma cell line changed the pattern of alternative splicing after irradiation with ultraviolet light or induction of melanogenesis; this suggests that corticotropin releasing factor receptor alternative splicing may be regulated by common stressors, through modifications of activity and/or availability of splicing factors.
J Invest Dermatol 2002 Jun
PMID:Corticotropin releasing factor receptor type 1: molecular cloning and investigation of alternative splicing in the hamster skin. 1206 Apr 4

The neuro-immuno-cutaneous-endocrine network is not a simple construct featuring organ systems intimately involved in the bridge between body and mind. Mind-body influences are bi-directional and the skin should be considered an active neuroimmunoendocrine interface, where effector molecules of neuropeptides act as common words used in a dynamic dialogue between brain, immune system and skin. Gamma-melanocyte stimulating hormone (gamma-MSH), one of the principal neuroimmunomodulating peptides, seems to exercise some control on the cutaneous inflammatory process, through a central action mediated by descending anti-inflammatory neural pathways and via local direct influence on inflammatory cells infiltrating the dermis, such as monocytes, macrophages and neutrophils. Gamma-MSH down-regulates the production of proinflammatory cytokines, while the production of the anti-inflammatory cytokine IL-10 is stimulated by gamma-MSH. Finally, gamma-MSH seems to regulate the expression of surface molecules in immunocompetent cells. Thus, further studies may lead to the use of gamma-MSH as an important anti-inflammatory agent in clinical dermatology.
Int J Dermatol 2002 Jun
PMID:Can the brain inhibit inflammation generated in the skin? The lesson of gamma-melanocyte-stimulating hormone. 1210 Jun 82

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.
Australas J Dermatol 1969
PMID:The influence of hormones on melanogenesis. 1230 81

Based on the clinical presentation of some skin pigmentation disorders it is thought that a bicompartmental functional system exists in the epidermal melanocyte population. It corresponds to the perifollicular and interfollicular compartments, respectively. The present study was undertaken looking for the presence of such a system on scalp unaffected by pigmentary disorders. The scalps of 100 men with incipient to severe androgenic alopecia were examined using a videocamera equipped with an internal ultraviolet light-emitting unit. The face, trunk and limbs were similarly examined in 45 of these adults and in 13 children of both sexes. In 92 men, a subclinical hypermelanosis was found as a speckled pattern centered on every single follicle. With increasing baldness severity, another epidermal hyperpigmentation pattern involving the interfollicular area was superimposed to the perifollicular pattern. These stereotyped patterns of subclinical melanoderma were also disclosed on the face of adults, but not in children. In addition, the spotty perifollicular pattern was discrete or not apparent on the other parts of the body. It is concluded that the perifollicular subclinical melanotic pattern is a regional characteristic of cephalic skin, perhaps related to the local production of melanocortins, particularly alpha-MSH by the pilosebaceous unit.
Eur J Dermatol
PMID:Subclinical speckled perifollicular melanosis of the scalp. 1245 29

Alpha-melanocyte stimulating hormone (alpha-MSH) has pigmentary, anti-inflammatory, antipyretic, and general immunomodulatory roles. It can oppose several cytokines including tumor necrosis factor-alpha in a number of tissues, including skin. We have previously shown that alpha-MSH can inhibit tumor necrosis factor-alpha stimulated intercellular adhesion molecule 1 upregulation and nuclear factor kappaB (NFkappaB) transcription factor activation in melanocyte and melanoma cells. It is thought, however, that this MSH biology may also extend to other cells of the skin and in this study we extend our work to keratinocytes. We have investigated in detail the ability of three alpha-MSH peptides to inhibit tumor necrosis factor alpha stimulated NFkappaB activation in nonpigmentary HaCaT keratinocytes (alpha-MSH, L-Lys-L-Pro-L-Val, and L-Lys-L-Pro-D-Val) and two adrenocorticotropic hormone (ACTH) peptides (1-17 and 1-39), reported to be present in skin tissue. NFkappaB/p65 activation was analyzed by electrophoretic mobility shift assay and immunofluorescent microscopy. alpha-MSH, L-Lys-L-Pro-L-Val, and L-Lys-L-Pro-D-Val all significantly inhibited tumor necrosis factor alpha stimulated NFkappaB activation, whereas ACTH 1-17 and 1-39 did not, in the HaCaT keratinocytes. MSH peptides and ACTH 1-39 were effective, however, at inhibiting NFkappaB activation in normal human keratinocytes. Immunolabeling of inhibitor kappaBalpha of NFkappaB (IkappaBalpha) revealed an abnormal localization to the nucleus of HaCaT cells, which was unaffected by MSH/ACTH peptides. In contrast, normal human keratinocytes showed a normal IkappaBalpha distribution that responded to MSH/ACTH with nuclear translocation. Our data support previous work on the role of MSH/ACTH peptides as immunomodulatory/anti-inflammatory regulators, and extend this work to keratinocytes identifying a novel IkappaBalpha mechanism and extends findings to ACTH peptides, identifying an abnormal IkappaBalpha mechanism in the immortal HaCaT versus normal keratinocyte.
J Invest Dermatol 2002 Dec
PMID:Inhibition of tumor necrosis factor-alpha stimulated NFkappaB/p65 in human keratinocytes by alpha-melanocyte stimulating hormone and adrenocorticotropic hormone peptides. 1248 24

Ultraviolet B radiation increases DOPA-positive melanocytes in the skin specifically at the site of exposure. We found unexpectedly that ultraviolet B irradiation of the eye increased the concentration of alpha-melanocyte-stimulating hormone in plasma and systemically stimulated epidermal melanocytes in mice. To test the possible involvement of hypothalamopituitary proopiomelanocortin system in the systemic activation of skin melanocytes, ultraviolet B was also irradiated to the eye after hypophysectomy. Hypophysectomy strongly inhibited the ultraviolet B-induced stimulation of melanocytes. To elucidate the pathway by which ultraviolet B irradiation of the eye activated the hypothalamopituitary system, we examined the effect of bilateral ciliary ganglionectomy and denervation of the optic nerves on the ultraviolet B-induced melanocyte stimulation. Ciliary ganglionectomy, but not optic nerve denervation, strongly inhibited melanocyte stimulation by localized irradiation of the eye. Furthermore, melanocyte stimulation by localized ultraviolet B irradiation of the eye was not observed in mice that lack the inducible type of nitric oxide synthase. These results clearly indicate that a signal evoked by ultraviolet B irradiation of the eye is transmitted in a nitric oxide-dependent manner through the ciliary ganglia involving the first branch of the trigeminal nerve to the hypothalamopituitary proopiomelanocortin system, resulting in upregulation of alpha-melanocyte-stimulating hormone secretion and consequent stimulation of melanocytes in the skin. The novel network involving the trigeminal nerve and nitric oxide-dependent signaling pathway might play important parts in the activation of proopiomelanocortin-dependent biologic reactions, such as alpha-melanocyte-stimulating hormone-induced stimulation of melanocytes in the skin, in ultraviolet B-enriched environments.
J Invest Dermatol 2003 Jan
PMID:Ultraviolet B irradiation of the eye activates a nitric oxide-dependent hypothalamopituitary proopiomelanocortin pathway and modulates functions of alpha-melanocyte-stimulating hormone-responsive cells. 1253 8


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