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

In mouse the melanocortin 5 receptor is known to regulate sebaceous gland function. To clarify its role in man, we have studied melanocortin 5 receptor expression in skin, and allelic variation at the melanocortin 5 receptor locus in diverse human populations and candidate disease groups. Melanocortin 5 receptor protein and mRNA expression were studied by immunohistochemistry and reverse transcriptase polymerase chain reaction. Melanocortin 5 receptor mRNA was detected in normal skin and cultured keratinocytes but not in cultured fibroblasts or melanocytes. Immunohistochemistry revealed melanocortin 5 receptor immunoreactivity in the epithelium and appendages, including the sebaceous gland, eccrine glands, and apocrine glands, as well as low level expression in the interfollciular epidermis. In order to screen for genetic diversity in the melanocortin 5 receptor that might be useful for allelic association studies we sequenced the entire melanocortin 5 receptor coding region in a range of human populations. One nonsynonymous change (Phe209Leu) and four synonymous changes (Ala81Ala, Asp108Asp, Ser125Ser, and Thr248Thr) were identified. Similar results were found in each of the populations except for the Inuit in which only the Asp108Asp variant was seen. The apparent "global distribution" of melanocortin 5 receptor variants may indicate that they are old in evolutionary terms. Variation of melanocortin 5 receptor was examined in patients with acne (n = 21), hidradenitis supprativa (n = 4), and sebaceous gland lesions comprising sebaceous nevi, adenomas, and hyperplasia (n = 13). No additional mutations were found. In order to determine the functional status of the Phe209Leu change, increase in cAMP in response to stimulation with alpha-melanocyte-stimulating hormone was measured in HEK-293 cells transfected with either wild-type or the Phe209Leu variant. The variant melanocortin 5 receptor was shown to act in a concentration-dependent manner, which did not differ from that of wild type. We have therefore found no evidence of a causative role for melanocortin 5 receptor in sebaceous gland dysfunction, and in the absence of any association between variation at the locus and disease group, the pathophysiologic role of the melanocortin 5 receptor in man requires further study.
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PMID:Expression, candidate gene, and population studies of the melanocortin 5 receptor. 1128 24

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.
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PMID:Evidence for expression of melanocortin-1 receptor in human sebocytes in vitro and in situ. 1187 95

A 31-year-old woman presented with progressive weight gain, facial acne, round facies, hirsutism, and secondary amenorrhea. Her plasma cortisol, urinary free cortisol, and plasma ACTH were elevated. CT scan of abdomen revealed bilateral diffuse adrenal enlargement. MRI of pituitary failed to identify a lesion. CT scan of chest revealed an 8 mm nodule in the lower lobe of the left lung. The diagnosis of ectopic Cushing's syndrome was made. The lung tumor was surgically removed. The tumor measured up to 1.5 cm in diameter. By light microscopy, a tumor with characteristic features of bronchial carcinoid was noted. Immunostains were positive for neuron-specific enolase, synaptophysin, chromogranin, low-molecular-weight keratin, ACTH, beta endorphin, corticotropin-releasing hormone, bombesin, alpha subunit, and somatostatin. Electron microscopy revealed an endocrine neoplasm. The secretory granules displayed great variation subdividing the endocrine neoplasm. The secretory granules displayed great variation subdividing the cell population into an undetermined number of phenotypes. In situ hybridization demonstrated positivity for pro-opiomelanocortin mRNA in the tumor cells. Postoperatively, plasma cortisol had fallen. The patient remained symptom-free one year later. The case presented here was regarded as a plurihormonal bronchial carcinoid associated with ectopic Cushing's syndrome. This unique plurihormonal bronchial carcinoid tumor produced three hormones, ACTH, CRH, and bombesin, that may have contributed to the patient's ectopic Cushing's syndrome.
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PMID:Plurihormonal Bronchial Carcinoid Associated with Ectopic Cushing's Syndrome. 1211 73

A 32-year-old woman with an ectopic adrenocorticotropic hormone (ACTH)-secreting pituitary adenoma (EAPA) is presented. She had rapidly gained weight and suffered recurrent facial acne for a few years but lacked the typical Cushingoid features. Endocrine examinations revealed that her plasma ACTH was markedly high (196 to 280 pg/ml) without showing normal circadian rhythm and failed to respond to corticotropin-releasing hormone stimulation. Her cortisol levels ranged from 22 to 30 microg/dl throughout observation but low doses (1 and 2 mg) of dexamethasone failed to suppress either ACTH or cortisol level. Magnetic resonance imaging study revealed a 3-cm mass occupying the sphenoidal sinus with partial enhancement by gadolinium, which was separated from the normal pituitary in the sella region. The tumor resected by transsphenoidal surgery was histologically diagnosed as an ACTH-producing pituitary adenoma. After surgery her weight gain and acne remitted in accordance with decreases in plasma ACTH. Analysis of patient plasma by gel filtration method revealed the existence of big ACTH molecules eluted with a peak of authentic 1-39 ACTH, suggesting that this biologically less-active ACTH might be the reason why overt features of Cushing's syndrome failed to develop in this case. Although EAPA is clinically rare in parasellar disorders, the presence of ectopic pituitary adenoma should be considered in such cases showing ACTH hypersecretion without typical Cushingoid features.
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PMID:An aberrant ACTH-producing ectopic pituitary adenoma in the sphenoid sinus. 1500 15

A case of unusual combination of polycystic ovaries (PCO), adrenal non-functioning adenoma and severe hirsutism in a young woman from Southern Italy is reported here. A 18-yr-old woman was referred to our Department because of oligomenhorrea, acne and severe hirsutism. During evaluation of the cause of her symptoms, PCO and small left adrenal adenoma were revealed. Although adrenal androgen excess has been shown to dysregulate the hypothalamic-pituitary-gonadal axis, causing PCO-like syndrome, normal circulating androgen values were found. Androgens and cortisol levels were completely suppressed by low-dose dexamethasone test, excluding autonomous steroid secretion by the adrenal mass. Normal response of cortisol and adrenal androgens to corticotropin stimulation test permitted the exclusion of functional adrenal hyperandrogenism. Despite normal LH/FSH ratio, anovulatory cycles were revealed by persistently low progesterone values. Glucose and insulin response to oral glucose tolerance test did not differ from those of normal population. The patient showed an improvement of acne and hirsutism on therapy with estro-progestins (EP). In conclusion, despite normal pattern of serum androgens and LH/FSH ratio, this patient had anovulatory cycles and good response to the EP treatment. These findings suggest that ultrasonography evidence of PCO together with anovulatory cycles contributed to her clinical picture whereas adrenal adenoma seemed to have no relevant role. This case report underlines the need of cautious interpretation of imaging results and clinical signs of severe hirsutism, reminding one that the true cause of a medical problem may not be the most evident.
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PMID:Adrenal adenoma and normal androgen levels in a young woman with polycystic ovaries: a case of idiopathic hirsutism? 1505 46

A causative link between emotional stress and acne has long been postulated. There is mounting evidence that the molecular mechanism underlying this observation is related to the expression of receptors for several neuroendocrine mediators by the sebaceous gland. Recent and ongoing studies have indicated that human sebocytes express functional receptors for corticotropin-releasing hormone, melanocortins, beta-endorphin, vasoactive intestinal polypeptide, neuropeptide Y and calcitonin gene-related peptide. After ligand binding, these receptors modulate the production of inflammatory cytokines, proliferation, differentiation, lipogenesis and androgen metabolism in sebocytes. By means of their autocrine, paracrine and endocrine actions, these neuroendocrine factors appear to mediate centrally and topically induced stress towards the sebaceous gland, ultimately affecting the clinical course of acne.
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PMID:Neuroendocrine regulation of sebocytes -- a pathogenetic link between stress and acne. 1550 10

Central or peripheral stress may induce the development of clinical inflammation in the pilosebaceous unit, leading to the development of acne lesions or to exacerbation of pre-existing acne. Melanocortin peptides such as alpha-melanocyte-stimulating hormone and its receptors do not only regulate melanogenesis but can also affect non-pigmentary processes, such as inflammation, apoptosis and sebogenesis. The purpose of the study was to investigate by immunohistochemistry if changes of melanocortin-1 receptor expression exist in acne lesions versus normal skin. In all, 33 patients with acne vulgaris and seven age-matched volunteers without acne participated in the study. Skin biopsies were taken from acne-involved faces, the non-involved thigh skin of the same patients and from normal human skin. Melanocortin-1 receptor immunoreactivity was most prominently detectable in adnexal structures. Sebocytes and keratinocytes of the ductus seboglandularis of acne-involved and non-involved skin showed very intense melanocortin-1 receptor expression in contrast to less intense scattered immunoreactivity in normal skin samples. These data suggest that melanocortin-1 receptor is involved in the pathogenesis of acne.
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PMID:Increased in situ expression of melanocortin-1 receptor in sebaceous glands of lesional skin of patients with acne vulgaris. 1757 33

There is compelling evidence that the sebaceous gland is not only a passive endocrine target organ that reacts to sex hormones with well established responses but also plays an integral and active part of various neuroendocrine/neuromediator axes within the skin. In this review, our current knowledge on the expression, regulation, and function of melanocortin peptides, corticotropin-releasing hormone, endogenous opioids including their receptors, and of other neuromediators, in normal and diseased human sebocytes will be described. Understanding the function of these newly recognized players in sebocyte biology will extend our present pathogenetic concepts of acne and related diseases. Moreover, these newly discovered mediators and their receptors in human sebocytes form a rich basis for the future design of neuroendocrine therapies for patients with sebaceous gland disorders.
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PMID:Neuroendocrine regulators: Novel trends in sebaceous gland research with future perspectives for the treatment of acne and related disorders. 2043 81

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

Cushing syndrome is the constellation of signs and symptoms caused by protracted exposure to glucocorticoids. The most common cause of Cushing syndrome in children and adolescents is exogenous administration of glucocorticoids. Presenting features commonly include weight gain, growth retardation, hirsutism, obesity, striae, acne and hypertension. Almost invariably, linear growth is severely diminished, a factor which may be useful in differentiating between childhood obesity and Cushing syndrome. Diagnostic approaches are based on distinguishing between adrenocorticotropic hormone (ACTH)-dependent and ACTH-independent etiologies, and consideration of the most likely diagnosis by age. Treatment modality is dependent upon etiology. After cure, important components of care include attention to linear growth, pubertal progression and body composition.
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PMID:Cushing syndrome. 2406 68


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