Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P01189 (beta-endorphin)
 21,003 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Clinical status, skin biopsy specimens, and endocrine function were evaluated in normal-coated Pomeranians (n = 12) and Pomeranians affected with growth hormone (GH)-responsive dermatosis (n = 7), then were compared with values in mixed-breed dog controls (n = 19). All Pomeranians were clinically normal; however, the Pomeranians with GH-responsive dermatosis had bilateral alopecia and hyperpigmentation of the trunk, caudal portion of the thighs, and ventral neck region. Skin biopsy specimens from the affected Pomeranians had decreased-to-normal epidermal thickness and follicular atrophy, compared with normal-coated Pomeranians. Numerous elastin fibers were observed in the skin biopsy specimens of unaffected and affected Pomeranians. Both groups of Pomeranians had normal results of thyrotropin-releasing hormone (TRH) and thyrotropin (TSH) response, adrenocorticotropin (ACTH) stimulation, and dexamethasone suppression testing. There was no significant increase in serum GH concentration in either group of Pomeranians after xylazine or human GH-releasing factor (GHRF) administration, whereas control dogs had significant (P less than or equal to 0.05) increase in serum GH concentration after administration of either agent. Baseline plasma ACTH concentration in unaffected and affected Pomeranians was increased above the normal range (40 to 90 pg/ml). Post-ACTH administration serum progesterone, 17-hydroxyprogesterone, and androgen (dehydroepiandrosterone sulfate or androstenedione) concentrations were consistently high in unaffected and affected Pomeranians, compared with values in control dogs.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hormonal abnormalities in Pomeranians with normal coat and in Pomeranians with growth hormone-responsive dermatosis. 217 97

Alterations in the hypothalamic-pituitary-adrenal (HPA) system are well documented in affective disorders. In depression these include increased secretion of cortisol, an insufficient suppressibility of cortisol by dexamethasone, a blunted corticotropin (ACTH) response to corticotropin-releasing hormone (CRH) and a dysfunction of the glucocorticoid receptor. Patients with atopic eczema, a common chronic skin disease, show seasonal variations in disease activity, symptoms of minor depression and immunological disturbances similar to those seen in patients with depression. To explore the integrity of the HPA system integrity in individuals with atopic eczema we studied the 24-h cortisol secretion and the cortisol, ACTH and beta-endorphin responses to CRH in such individuals and in healthy controls matched for sex and age. The 24-h secretion of cortisol did not differ between the patients with atopic eczema and the controls. The net response to CRH administered as a 100 micrograms i.v. bolus was significantly attenuated for both cortisol (24,235 +/- 12,443 vs. 47,019 +/- 34,515 nmol.min/dl; p < .03) and for ACTH (546 +/- 205 vs. 727 +/- 310 pmol.min/l; p < .05) in the patient group, whereas the beta-endorphin response did not differ between the groups (1072 +/- 448 vs. 1603 +/- 421 nmol.min/l). The blunted response of cortisol and ACTH cannot be explained by hypercortisolism as it is the case in major depression. Rather, it may be related to a prolonged underexposure to hypothalamic CRH or to an increased sensitivity of glucocorticoid feedback inhibition.
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PMID:Cortisol, corticotropin, and beta-endorphin responses to corticotropin-releasing hormone in patients with atopic eczema. 767 38

Proopiomelanocortin (POMC) is known to be synthesized in the pituitary gland and is subsequently cleaved by specific prohormone convertases into biologically active peptide hormones such as melanocyte stimulating hormones (MSH), adrenocorticotropin (ACTH) and endorphins (EP). Guanine nucleotide-binding protein (G-protein)-coupled receptors, which have only recently been discovered, are involved in the transmission of their message. There is also evidence indicating that POMC is not only produced by pituitary cells but is an ubiquitous molecule, that is cleaved cell- and tissue-specific. It has also been shown that the epidermis keratinocytes as well as melanocytes express POMC upon stimulation and release alpha MSH and ACTH. In addition to their function as hormones, POMC peptides have been shown to exert a variety of immunoregulatory effects by modulating the function of immunocompetent cells as well as cytokines. These findings provide further evidence for the immunoneuroendocrine network playing a crucial role during the pathogenesis of immune and inflammatory skin disease.
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PMID:Proopiomelanocortin production by epidermal cells: evidence for an immune neuroendocrine network in the epidermis. 772 41

A 21-year-old female with atopic dermatitis showed "dependence" on very hot hot-spring bathing. Her skin disease had been refractory to various treatments including steroid therapy for a long time. Without medical supervision she took four 3-minute 47 degrees C hot-spring baths daily for a month for the purpose of improving her skin symptom. Subsequently, she could not stop bathing in very hot hot-spring water of her own will. However, a month's isolation in a hospital relieved her of the situation. The mechanism of the dependence on very hot hot-spring bathing may be explained by a transient rise in the plasma beta-endorphin level due to hyperthermal stress.
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PMID:Dependence on very hot hot-spring bathing in a refractory case of atopic dermatitis. 773 Jul 38

We investigated the presence of proopiomelanocortin (POMC) products in sections of skin from normal subjects and patients with neoplastic and non-neoplastic cutaneous disorders. Antibodies specific against adrenocorticotropin, beta-melanotropin, and beta-endorphin were used for detection and characterization of cell types bearing POMC peptides. POMC products were not observed in sections of normal skin from the corporal (non-scalp) areas (six cases), whereas the hair follicles of scalp skin exhibited positive immunostains that were readily apparent (four cases). POMC products were frequently detected in corporal skin affected by diseases (13 of 26 cases), for example, psoriatic keratinocytes, the inflammatory infiltrate in scarring alopecia, nevocytes, the epithelial cell nests of basal cell carcinoma, and melanoma cells. Further tests were performed in keloids, a primary reactive skin disorder, to evaluate whether POMC accumulation represented a disease-related phenomenon or an expression of normal cutaneous reactivity. POMC products were consistently detected (10 of 11 cases) in the keratinocytes and mononuclear cells at keloid lesions. Thus these observations indicate that POMC products may accumulate locally in lesional skin representing, presumably, a novel cutaneous response to injury. The broad spectrum of POMC products detected suggests that these arise from production in situ (expression of the POMC gene itself) by human skin.
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PMID:Detection of proopiomelanocortin-derived antigens in normal and pathologic human skin. 824 78

Atopic eczema is a chronic inflammatory skin disease which shares some psychological and neuroendocrine disturbances with patients suffering from depression. In view of recent findings of an attenuated response of the hypothalamic-pituitary-adrenal (HPA) system in patients with atopic eczema during a human corticotropin-releasing hormone (hCRH) challenge paradigm fourteen consecutive non-specifically trained in-patients with atopic eczema (8 men, 6 women) and an age-matched control group (8 men, 6 women) performed exhausting incremental graded bicycle exercise to evaluate cortisol, adrenocorticotropin (ACTH), beta-endorphin, epinephrine and norepinephrine releases induced by physical stress. The exercise yielded significant increases in cortisol, ACTH, beta-endorphin, epinephrine and norepinephrine concentrations in both groups. Patients with severe eczema displayed a significantly lower increase in norepinephrine levels when compared with the less affected patient group. In contrast to the challenge with exogenous hCRH no substantial difference in the net responses of ACTH and cortisol could be detected between patients with atopic eczema and controls using the physical stress paradigm. These substantial differences in the net outcome between both challenges may be related to the potential synergizing effects of various neuropeptides, e.g. CRH and vasopressin, when activating the HPA system by challenges at a suprapituitary site which may override subtle disturbances in the responsivity of the HPA system as revealed by CRH challenge alone in patients with atopic eczema.
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PMID:Physical stress-induced secretion of adrenal and pituitary hormones in patients with atopic eczema compared with normal controls. 908 93

Psychological stress is known to aggravate inflammatory skin diseases such as atopic dermatitis, psoriasis and contact sensitivity by altering the cellular constituents of the immune system. The skin appendages function dually as prominent targets and sources of the peripheral corticotropin-releasing hormone-proopiomelanocortin (CRH-POMC) axis. In this study, we examined the expression level of CRH-POMC axis constituents in psoriasis, a well-known stress-related inflammatory skin disease. The 15 psoriasis patients and six normal controls were retrospectively selected after extensive review of their clinical records and skin biopsy specimens. We immunohistochemically analysed the expressivity of CRH, adrenocorticotrophic hormone (ACTH) and alpha-melanocyte-stimulating hormone (alpha-MSH) in various types of psoriatic lesions and control skin. A significant increase of CRH expression was observed in psoriatic lesions, which involved the entire epidermis (upper layer in particular), hair follicles and sweat glands compared with controls. Expression of ACTH and alpha-MSH was clearly stimulated in a subset of psoriasis patients compared with controls, but on the whole, lacked statistical significance. The immunoreactivity of CRH, ACTH and alpha-MSH in psoriasis was not dependent on its clinical subtype, duration or number of previous treatments. Compared with the definite increase of CRH expression in psoriasis, the expression of the POMC peptides was heterogenous with no overall significance. From the findings, we suggest that CRH, a key stress hormone, may play an important role in the pathomechanism of psoriasis.
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PMID:Expression of the corticotropin-releasing hormone-proopiomelanocortin axis in the various clinical types of psoriasis. 1722 23

Acne is the most common inflammatory skin disease in which IL-1 plays a central role. Although alpha-melanocyte-stimulating hormone has immunomodulatory effects, its usefulness as an anti-inflammatory agent in acne is hampered owing to its lipid- and pigment-inducing effects via activation of melanocortin receptors (MC-Rs). We used the immortalized human sebocyte line SZ95 as an in vitro model to investigate the anti-inflammatory potential of KdPT, a tripeptide derivative of the C-terminal end of alpha-melanocyte-stimulating hormone. KdPT potently suppressed IL-1beta-induced IL-6 and IL-8 expression. Mechanistically, KdPT decreased IL-1beta-mediated IkappaBalpha degradation, reduced nuclear accumulation of p65, and attenuated DNA binding of NF-kappaB. Moreover, KdPT reduced IL-1beta-mediated generation of intracellular reactive oxygen species, which contributed to IL-1beta-mediated cytokine induction. KdPT also reduced cell surface binding of fluorochrome-labeled IL-1beta in SZ95 sebocytes. Analysis of the crystal structure of the complex between IL-1beta/IL-1R type I (IL-1RI), followed by computer modeling of KdPT and subsequent modeling of the peptide receptor complex with the crystal structure of IL-1RI via manual docking, further predicted that the tripeptide, through several H-bonds and one hydrophobic bond, interacts with the IL-1RI. Importantly, KdPT did not bind to MC-1Rs, as demonstrated by blocking experiments with a peptide analog of Agouti signaling protein and by binding assays using MC-1R-expressing B16 melanoma cells. Accordingly, KdPT failed to induce melanogenesis. Our data demonstrate a promising anti-inflammatory potential of KdPT and point toward novel future directions in the treatment of acne-as well as of various other IL-1-mediated inflammatory diseases-with this small molecule.
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PMID:KdPT, a tripeptide derivative of alpha-melanocyte-stimulating hormone, suppresses IL-1 beta-mediated cytokine expression and signaling in human sebocytes. 2061 Jun 47

Atopic dermatitis (AD), also known as atopic eczema, is chronic pruritic skin disease. AD can increase psychological stress as well, increasing glucocorticoid release and exacerbating the associated symptoms. Chronic glucocorticoid elevation disturbs neuroendocrine signaling and can induce neuroinflammation, neurotoxicity, and cognitive impairment; however, it is unclear whether AD-related psychological stress elevates glucocorticoids enough to cause neuronal damage. Therefore, we assessed the effects of AD-induced stress in a mouse AD model. AD-related psychological stress increased astroglial and microglial activation, neuroinflammatory cytokine expression, and markers of neuronal loss. Notably, melatonin administration inhibited the development of skin lesions, scratching behavior, and serum IgE levels in the model mice, and additionally caused a significant reduction in corticotropin-releasing hormone responsiveness, and a significant reduction in neuronal damage. Finally, we produced similar results in a corticosterone-induced AD-like skin model. This is the first study to demonstrate that AD-related psychological stress increases neuroendocrine dysfunction, exacerbates neuroinflammation, and potentially accelerates other neurodegenerative disease states.
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PMID:Melatonin inhibits neuronal dysfunction-associated with neuroinflammation by atopic psychological stress in NC/Nga atopic-like mouse models. 2850 Jul 66

Acne is a multifactorial dermatosis, which is influenced not only by hormones but also by the biochemical relationship between them and the pilosebaceous unit. Inflammatory cytokines, chemokines, active oxygen, and zinc are known to be associated with the development of acne. Further, steroid metabolism is known as one of the important factors related to sebum secretion and comedone formation in acne. However, there is a lack of studies comparing these human biomarkers between healthy individuals and patients with acne. In particular, no study has investigated the relationship between human biomarkers and patterns of acne yet.The purpose of this study is to investigate diagnostic human biomarkers in acne by comparing the biological and metabolic biomarkers between healthy individuals and patients with acne and identify the relationship between human biomarkers and patterns of acne.This study is a protocol for a cross-sectional study. Forty healthy participants and 60 patients with acne will be recruited at 1 center. We will collect their blood samples and analyze the molecular biological and metabolic biomarkers (cytokines, chemokines, reactive oxygen species, corticotropin-releasing hormone, zinc, amino acid, 1-carbon metabolite, lipid metabolite, etc.). Further, we will administer questionnaires regarding their diet, sleep, stress, and other factors relating to acne and measure their skin elasticity.The study protocol was approved by the Institutional Review Board of Oriental Medical Hospital at Kyung Hee Medical Center (KOMCIRB-161118-HR-062). Written informed consent will be obtained from all the participants. The trial was registered in the Clinical Research Information Service, Republic of Korea: KCT0002212.This trial will provide evidence regarding diagnostic human biomarkers in acne and the relationship between the human biomarkers and patterns of acne.
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PMID:A comparative study of biological and metabolic biomarkers between healthy individuals and patients with acne vulgaris: A cross-sectional study protocol. 2913 71


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