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)

We investigated the effects of various hormones and growth factors on aromatase activity in cultured human skin fibroblasts. Several potential trophic factors were tested for their ability to modify basal aromatase activity or the response to dibutyryladenosine 3',5'-cyclic monophosphate and dexamethasone because (i) no endogenous ligand has been identified that is responsible for stimulating aromatase activity in the periphery, and (ii) dexamethasone and cAMP analogs can increase this enzyme's activity in fibroblasts. The effect of insulin and insulin-like growth factors were examined in closer detail because of the clinical association between insulin and hyperandrogenism. Pituitary hormones and hypothalamic releasing factors, such as human ACTH (10 nM), beta-endorphin (10 nM), beta-lipotropin (10 nM), alpha-MSH (10 nM), gamma 3-MSH (10 nM), ovine luteinizing hormone (10 ng/ml), ovine follicle-stimulating hormone (10 ng/ml), ovine thyroid-stimulating hormone (10 ng/ml), rat growth hormone (10 ng/ml), rat prolactin (10 ng/ml), rat corticotropin-releasing factor (10 nM), luteinizing hormone-releasing factor (10 nM), thyrotropin-releasing factor (10 nM), human growth hormone-releasing factor (10 nM), and somatostatin (10 nM), have no significant effects on aromatase activity. Porcine inhibin A (10 ng/ml) and porcine activin AB (10 ng/ml), two ovarian hormones with structural transforming homology to transforming growth factor-beta, also have no effect on aromatase activity. Although basic fibroblast growth factor (1-100 ng/ml), acidic fibroblast growth factor (1 ng/ml), epidermal growth factor (1 ng/ml), platelet-derived growth factor (1 ng/ml), tumor necrosis factor (1 ng/ml), and transforming growth factor-beta 1 (1 ng/ml) have no effect on basal aromatase activity in human skin fibroblasts, all of these growth factors inhibited the ability of dibutyryladenosine 3',5'-cyclic monophosphate to stimulate aromatase activity. In contrast, both insulin (100 pg/ml-10 ng/ml) and insulin-like growth factor-1 (1-100 ng/ml) had no effect on cAMP-stimulated aromatase but potentiated the action of dexamethasone (100 nM). Thus, there is a clear distinction between the effects of dexamethasone and cAMP on peripheral aromatase. On the basis of the results presented here, it is interesting to speculate that the hyperandrogenism that is often associated with insulin resistance may be due to a combination of growth factor-mediated inhibition of aromatase activity and the failure of peripheral tissues to respond to insulin and metabolize androgens to estrogens.
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PMID:Growth factor-mediated regulation of aromatase activity in human skin fibroblasts. 167 98

The author studied the content of corticotropin, cortisol, aldosterone, insulin in the blood serum of 69 patients with rheumatoid arthritis depending on the grade of activity of the inflammatory process before treatment in the course of aurotherapy within 12 months. It was established that in patients with rheumatoid arthritis changes develop in the system of pituitary-peripheral endocrine glands, namely, an increase of the concentration of corticotropin, aldosterone and a reduction of the level of cortisol and insulin indicating the participation of hormones in the pathogenesis of rheumatoid arthritis. Non-steroid antiinflammatory preparations and quinolinic derivatives did not effect the hormonal spectrum of rheumatoid arthritis. Prolonged aurotherapy resulted in a positive dynamics in the contents of hormones.
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PMID:[The effect of aurotherapy on the content of corticotropin, cortisol, aldosterone and insulin in the blood serum of rheumatoid arthritis patients]. 167 83

Previous studies of the amino acid analogue, alpha-ketoisocaproate (KIC), indicate that it can stimulate lymphocyte blastogenesis and antibody responses of sheep. To determine whether KIC could overcome the effects of adrenocorticotropic hormone (ACTH)-induced lymphocyte suppression, 24 lambs were fed a control diet, a diet supplemented with 0.05% KIC, or a diet supplemented with 0.05% of the parent amino acid leucine. Immune status was monitored by determining lymphocyte blastogenic responsiveness to phytohemagglutinin-P (PHA), concanavalin A (conA), and pokeweed mitogen (PWM) and percentages of T-cell subsets in the blood, using monoclonal antibodies and a flow cytometer. Serum cortisol, insulin, and glucagon concentrations also were determined. After 60 days of consuming the respective diet, lambs were administered either saline solution or ACTH (100 IU) twice daily for 3 consecutive days. Administration of ACTH increased serum cortisol and insulin concentrations; however, no effects were seen for serum glucagon concentration. Compared with saline administration, ACTH administration significantly (P less than 0.05) suppressed mitogen-stimulated lymphocyte blastogenesis by approximately 50%, regardless of the mitogen used, and significantly (P less than 0.01) decreased the percentage of circulating T lymphocytes and decreased (P less than 0.01) the ratio of T4 to T8 cells. Lambs fed KIC had greater PHA- and conA-stimulated blastogenic responses and significantly (P less than 0.05) increased ratio of T4 to T8 cells in the blood, compared with lambs fed the leucine-supplemented diet or the control diet and given corresponding injections. These data indicate that ACTH decreased in vitro lymphocyte blastogenesis and altered the subset ratios of blood lymphocytes in sheep. These changes were partially prevented by feeding KIC.
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PMID:Effects of alpha-ketoisocaproate on adrenocorticotropin-induced suppression of lymphocyte function in sheep. 167 50

Mouse melanoma cells in culture respond to melanocyte-stimulating hormone (MSH) or to cyclic AMP analogues by demonstrating an increase in tyrosinase activity. In this study the effect of the tumor promoter, 12-O-tetradecanoylphorbol 13-acetate (TPA), on the hormonal induction of tyrosinase was examined. TPA was found to lower basal levels of tyrosinase activity in melanoma cells and to reduce tyrosinase levels in cells treated with either MSH (10(-7) M), dibutyryl cAMP (10(-4) M), isobutylmethylxanthine (IBMX, 10(-4) M), or with the potent MSH analogue, [Nle4,D-phe7]-alpha-MSH. The phorbol ester, phorbol 12,13-dibutyrate was also effective in lowering tyrosinase activity levels, while 4 alpha-phorbol 12,13-didecanoate, which does not bind protein kinase C, was ineffective. In order to determine how TPA may reduce tyrosinase activity in melanoma cells, the levels of tyrosinase mRNA in untreated or TPA-treated cells were determined by Northern blot analysis. A marked down-regulation of constitutive levels of tyrosinase mRNA was observed in cells treated with the tumor promoter. Tyrosinase mRNA levels in cultures exposed to TPA for 48 h were only 7% of control levels. Tyrosinase mRNA levels in cells treated with both MSH and TPA were also lower than in cells treated with MSH alone. Previous studies from this laboratory have shown that insulin both lowers basal tyrosinase activity in melanoma cells and antagonizes the MSH stimulation of the enzyme. We have now determined that this inhibition is also due to reduced levels of tyrosinase mRNA.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Down-regulation of tyrosinase mRNA levels in melanoma cells by tumor promoters and by insulin. 170 21

Food intake can be increased or decreased after either central or peripheral administration of peptides. Galanin, neuropeptide Y, opioid peptides, growth-hormone-releasing hormone, and desacetyl-melanocyte stimulating hormone increase food intake whereas insulin, glucagon, cholecystokinin, anorectin, corticotropin-releasing hormone, neurotensin, bombesin, cyclo-his-pro, and thyrotropin-releasing hormone reduce food intake. Many of these peptides have reciprocal effects on food intake and sympathetic activity with those peptides that stimulate food intake reducing sympathetic activity and vice versa. In addition, neuropeptide Y specifically increases carbohydrate intake. Galanin and opioid peptides on the other hand increase fat intake whereas enterostatin reduces fat intake. Glucagon decreases protein intake. The effect of peptides on specific nutrients suggests that peptides may work in part by modulating basic feeding mechanisms to lead to the selection of specific nutrients from the diet. This hypothesis might be called a nutrient-specific model of peptide-induced food intake.
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PMID:Peptides affect the intake of specific nutrients and the sympathetic nervous system. 172 38

Adrenalectomy stimulates depressed brown adipose tissue (BAT) metabolism and decreases hyperinsulinemia in ob/ob mice, with minimal effects in lean mice. A single intracerebroventricular injection of dexamethasone (250 ng) into adrenalectomized ob/ob mice completely reversed the effects of adrenalectomy on BAT thermogenesis as assessed by mitochondrial GDP binding, approximately doubled plasma insulin, lowered whole body metabolic rates by 17%, and increased food intake by 19%. These responses were rapid in onset, with changes in BAT metabolism and plasma insulin occurring within 30 min of dexamethasone injection. Adrenalectomized lean mice were much less responsive to dexamethasone than their ob/ob counterparts. The dexamethasone-induced decrease in BAT thermogenesis in adrenalectomized ob/ob mice was associated with an organ-specific decrease in BAT sympathetic nerve activity as assessed by norepinephrine turnover, whereas the dexamethasone-induced increase in plasma insulin was blocked by atropine, suggesting involvement of the parasympathetic nervous system. Intracerebroventricular injection of corticotropin-releasing hormone did not affect BAT thermogenesis in dexamethasone-injected adrenalectomized ob/ob mice but markedly lowered plasma insulin concentrations, possibly by suppression of the parasympathetic nervous system. In conclusion, dexamethasone alters regulation of the autonomic nervous system in ob/ob mice.
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PMID:Glucocorticoids in the CNS regulate BAT metabolism and plasma insulin in ob/ob mice. 173 41

The present study was undertaken to evaluate the metabolic and hormonal responses to physiologic elevations of plasma beta-endorphin concentrations in both normal-weight and obese healthy subjects. The infusion of synthetic human beta-endorphin (4.5 ng/kg/min) produced the following: (1) in normal-weight subjects, no significant change of plasma glucose and pancreatic hormones (insulin, C-peptide, and glucagon), a significant plasma free fatty acids (FFA) increase, and a suppression of glycerol plasma levels; (2) in obese subjects, significant increases of glucose, insulin, C-peptide, and glucagon, a progressive decline of circulating FFA, and no change in glycerol plasma levels. In obese subjects, the intravenous administration of naloxone, given as a bolus (5 mg injected in 5 minutes) before the start of beta-endorphin infusion, reduced the plasma glucose response to the opioid by approximately half, annulled the pancreatic hormonal responses, and also reduced the FFA, but not glycerol, response. In normal-weight subjects, naloxone pretreatment did not induce any change of the flat glucose and hormonal responses to beta-endorphin, but reversed its effects on circulating FFA and glycerol. These data suggest that physiological elevations of plasma beta-endorphin concentrations produce metabolic and hormonal effects in obese subjects significantly different from those occurring in normal-weight subjects; these effects are partially naloxone-sensitive, suggesting the mediation of endogenous opioid receptors.
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PMID:Physiological elevations of plasma beta-endorphin alter glucose metabolism in obese, but not normal-weight, subjects. 173 41

It has been claimed that sucrose intake induces a rise in beta-endorphins. In an attempt to discriminate between the sensorial and metabolic effects of sucrose intake in this process, the effects of two chocolate drinks were compared: one sweetened with 50 g of sucrose, the other with 80 mg of aspartame. Plasma beta-endorphin concentrations were more elevated after the aspartame drink than after sucrose or fasting, while insulin increased after drinking as much with aspartame as with sucrose. We suggest that the increase in beta-endorphin after aspartame edulcorated chocolate is related with insulin secretion in the absence of marked changes in blood glucose or with a direct effect of aspartame itself on beta-endorphin liberation.
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PMID:Immunoreactive beta-endorphin increases after an aspartame chocolate drink in healthy human subjects. 180 84

The responses of plasma beta-endorphin, insulin and glucose to two different isocaloric mixed meals--high carbohydrate (CHO meal) and high fat (fat meal)--were assessed in women with android obesity before (n = 11) as well as after (n = 5) weight reduction, and in normal-weight controls (n = 8). Basal plasma beta-endorphin concentrations in the obese subjects (7.7 +/- 1.2 pmol/l) were significantly (p less than 0.005) higher than in the controls (3.8 +/- 0.5 pmol/l) and were not influenced by weight loss. Fasting plasma levels and the integrated releases of insulin and glucose, both after the CHO meal and after the fat meal were significantly higher in the obese subjects than in the controls. The fat meal induced no changes in beta-endorphin levels in either group. After the CHO meal a significant decrease in plasma beta-endorphin concentration was observed only in the obese group before weight reduction. An influence on beta-endorphin release by macronutrients is hypothesized.
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PMID:Beta-endorphin and insulin/glucose responses to different meals in obesity. 181 98

Many neuroendocrine precursor proteins, such as proopiomelanocortin (POMC), are cleaved in a tissue specific manner at distinct pairs of basic amino acids. Elucidating the specificity of the prohormone endoprotease(s) is essential to understanding cleavage specificity. However, isolation of these enzymes has been difficult, due to the inability to distinguish authentic maturation enzyme from the many other trypsin-like activities present in tissue homogenates. Recently, a "signature" of the insulin cell endoprotease(s) was defined in vivo by assessing the processing of a series of mutant cleavage sites in a model prohormone, mouse POMC (mPOMC) (Thorne, B. A., and Thomas, G. (1990) J. Biol. Chem. 265, 8436-8443. To investigate mechanisms of tissue-specific processing, we sought to identify the endoprotease signature of a cell having a processing phenotype distinct from insulinoma cells. In this report, the cleavage site specificity of the endoprotease(s) expressed in bovine adrenal chromaffin cells is examined. High levels of mPOMC (1.6 pmol/10(6) cells) were expressed in these cells using a vaccinia virus vector, and the precursor was targeted to the regulated secretory pathway. Analysis of POMC-derived peptides revealed that chromaffin cells processed the prohormone to a set of peptides highly similar to anterior pituitary corticotrophs, including adrenocorticotropin hormone (ACTH) and beta-lipotropin, gamma-lipotropin, and beta-endorphin. This processing contrasted with the pattern of cleavage site utilization in Rin m5F insulinoma cells, which more closely resembled that of the intermediate pituitary melanotrophs. However, the processing preference for the sequences of pairs of basic amino acids (as tested using the entire series of mutant cleavage sites; -LysArg- (native), -ArgArg-, -ArgLys-, -LysLys-, -HisArg-, -MetArg- at the ACTH/beta-lipotropin junction and -LysLys- (native), -LysArg-, -ArgArg-, -ArgLys- in beta-endorphin) was the same in both insulinoma and adrenal chromaffin cells, suggesting recognition and cleavage by similar enzymes in both cell types. The cell-specific processing of mPOMC may thus result from expression of a common core set of processing enzymes and factors unique to each cell type affecting the enzyme accessibility to precursor cleavage sites.
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PMID:Expression and processing of mouse proopiomelanocortin in bovine adrenal chromaffin cells. A model system to study tissue-specific prohormone processing. 185 97


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