Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

Dehydroepiandrosterone (DHEA) and its sulfate (DHEAS) are the main adrenal androgens (AAs) produced in humans. Production of these steroids, like that of cortisol, is under the control of hypothalamic corticotropin-releasing hormone (CRH) and pituitary ACTH. Other factors, however, appear to be involved in AA secretion because there are many instances in which their circulating levels do not change in parallel to those of cortisol. Apart from physiological alterations associated with fetal adrenal regression, adrenarche and aging, the main instances of divergence in AA production compared with those of corticosteroids occur when immune function is activated or is aberrant. Relative reductions in DHEA and DHEAS have been noted in subjects with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), human immunodeficiency virus (HIV) and autoimmune deficiency syndrome (AIDS), sepsis, and trauma. In some instances, differences in the AA responses have been linked to a clinical course. The mechanisms for impairments in AA production in the absence of suppressed corticoid secretion are unclear but may involve circulating cytokines or locally released mediators from immune system cells in the adrenal gland. There also is evidence that DHEA and DHEAS play a role in immune competence, displaying biological effects opposite to those of corticosteroids.
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PMID:Adrenal androgens and the immune system. 1563 95

Neurogenic inflammation and ensuing pain can be modulated by inhibiting the function of primary afferent neurons. The best studied mechanism to accomplish such inhibition is the opioid system. Under inflammatory conditions, the anterograde axonal transport of opioid receptors from dorsal root ganglia toward the peripheral sensory nerve endings is augmented. The increased number of opioid receptors (among other mechanisms) leads to improved analgesic effects of exogenously administered ligands (eg, morphine) and of endogenous leukocyte-derived opioid peptides (eg, beta-endorphin). A current concept proposes that during inflammatory processes endogenous opioid peptides can be secreted from immunocytes, occupy peripheral opioid receptors on sensory nerve endings, and produce analgesia by inhibiting the excitability of these nerves or the release of proinflammatory neuropeptides. This article focuses on the role of peripheral opioid receptors in pain control and on novel pharmaceutical concepts for the treatment of patients who suffer from rheumatoid arthritis and other inflammatory pain.
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PMID:Controlling pain by influencing neurogenic pathways. 1563 58

We review the evidence indicating a possible beneficial role for UVR on three Th1-mediated autoimmune diseases: multiple sclerosis, type 1 diabetes and rheumatoid arthritis in relation to recent developments in photoimmunology. Recent work suggests that UVR exposure may be one factor that can attenuate the autoimmune activity leading to these three diseases through several pathways involving UVB and UVA irradiation, UVR-derived vitamin D synthesis and other routes such as alpha-melanocyte-stimulating hormone, calcitonin gene related peptide and melatonin. Ecological features, particularly a gradient of increasing prevalence of multiple sclerosis and type 1 diabetes with higher latitude, provide some support for a beneficial role of UVR. Analytical studies provide additional support, particularly as low vitamin D has been prospectively associated with disease onset for all three diseases, but are not definitive. Randomized controlled trial data are required. Further, we discuss how associated genetic studies may assist the accumulation of evidence with regard to the possible causal role of low UVR exposure and/or low vitamin D status in the development of these diseases.
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PMID:UVR, vitamin D and three autoimmune diseases--multiple sclerosis, type 1 diabetes, rheumatoid arthritis. 1597 32

In China, the ethylacetate extract of the herb Tripterygium wilfordii Hook f (TWEE), containing the major active ingredient triptolide, is often used with favorable effect on rheumatoid arthritis patients, in alternation with the use of prednisone. The mechanism of this therapeutic effect, however, has not been completely delineated. In this study, we studied how TWEE and prednisone affect the pituitary and adrenal glands in rats. Thirty normal male Sprague-Dawley rats (ten per group) were randomly assigned to receive: (1) TWEE (25 mg/kg, twice a day), (2) prednisone (2 mg/kg, twice a day), or (3) vehicle (control) (0.5% sodium carboxymethyl cellulose 1 ml, twice a day), orally for 30 days. Pituitary and trunk blood were collected on day 31. Adrenocorticotropic hormone (ACTH) expression in the pituitary gland was assessed morphologically by immunohistochemical techniques. Plasma ACTH concentrations and serum corticosterone concentrations were quantitatively measured by radioimmunoassay. We found that TWEE significantly increased plasma ACTH concentration and serum corticosterone concentration and dramatically increased the number of ACTH-positive cells in the pituitary. Our findings indicate that TWEE can promote the synthesis and secretion of ACTH cells--in the pars distalis of the rat pituitary gland and the production of corticosterone in the zone fasciculata of the adrenal cortex. Our results indicate that TWEE has a cortical hormone-like function and can promote adrenal cortex function by activating the hypothalamus-pituitary-adrenal axis.
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PMID:Effects of the extract of a Chinese herb Tripterygium wilfordii hook f on rat pituitary gland. 1635 51

To assess adrenal function with respect to the presence or absence of steroid therapy, we investigated differences in the blood levels of adrenocorticotropic hormone (ACTH) and dehydroepiandrosterone sulfate (DHEAS) in relation to steroid (prednisolone) administration in 123 patients with rheumatoid arthritis (RA). Levels of ACTH and DHEAS were significantly lower in the steroid-treated group than in the non-treated group (ACTH: 11.79 pg/ml vs 27.92 pg/ml) (DHEAS: 418.12 ng/ml vs 883.91 ng/ml) (P<0.0001). We observed no steroid dose-related differences in ACTH levels. However, DHEAS levels showed a slight decrease at a prednisolone dose of 2.5 mg/day, with a significant decrease being observed at a dose of 5 mg/day when statistical adjustments were made for age and sex (P<0.0001). At doses of 7.5 mg/day or greater, DHEAS levels were significantly lower than those for 5 mg/day (P<0.0006). These results suggest that low-dose prednisolone reduces adrenal function in patients with RA. We recommend that doses of prednisolone should be limited to 5 mg/day or less in consideration of adrenal function when treating RA patients. The measurement of ACTH and DHEAS may be useful for evaluating adrenal function in patients with RA.
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PMID:Adrenocorticotropic hormone and dehydroepiandrosterone sulfate levels of rheumatoid arthritis patients treated with glucocorticoids. 1662 21

Recently, studies in adult rheumatoid arthritis patients have shown an association with four single-nucleotide polymorphisms (SNPs) in the 3.7-kb regulatory region of human corticotropin-releasing hormone (hCRH) gene located at positions -3531, -3371, -2353, and -684 bp. Three of these novel polymorphisms are in absolute linkage disequilibrium, resulting in three combined alleles, named A1B1, A2B1, and A2B2. To study whether the described polymorphic nucleotide sequences in the 5' region of the hCRH gene interfere with binding of nuclear proteins, an electric mobility shift assay (EMSA) was performed. At position -2353 bp, a specific DNA protein complex was detected for the wild-type sequence only, possibly interfering with a binding site for the activating transcription factor 6 (ATF6). In contrast, no difference could be detected for the other SNPs. However, at position -684, a quantitative difference in protein binding due to cAMP incubation could be observed. To further investigate whether these SNPs in the CRH promoter are associated with an altered regulation of the CRH gene, we performed a luciferase reporter gene assay with transiently transfected rat pheochromocytoma cells PC12. Incubation with 8-Br-cAMP alone or in combination with cytokines enhanced significantly the promoter activity in PC12 cells. The promoter haplotypes studied exhibited a differential capacity to modulate CRH gene expression. In all our experiments, haplotype A1B1 showed the most pronounced influence on promoter activity. Taken together, our results demonstrate a differential binding capacity of nuclear proteins of the promoter polymorphisms resulting in a different gene regulation. Most probably the SNP at position -2,353 plays a major role in mediating these differences.
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PMID:Sequence variants of the CRH 5'-flanking region: effects on DNA-protein interactions studied by EMSA in PC12 cells. 1685 32

Associations between stress and health outcomes have now been carefully documented, but the mechanisms by which stress specifically influences disease susceptibility and outcome remain poorly understood. Recent evidence indicates that glucocorticoids (GCs) and catecholamines (CAs), the major stress hormones, inhibit systemically IL-12, TNF-alpha, and INF-gamma, but upregulate IL-10, IL-4, and TGF-beta production. Thus, during an immune and inflammatory response, the activation of the stress system, through induction of a Th2 shift may protect the organism from systemic "overshooting" with T helper lymphocyte 1 (Th1)/proinflammatory cytokines. In certain local responses and under certain conditions, however, stress hormones may actually facilitate inflammation, through induction of IL-1, IL-6, IL-8, IL-18, TNF-alpha, and CRP production, and through activation of the corticotropin-releasing hormone (CRH)/substance P(SP)-histamine axis. Autoimmunity, chronic infections, major depression, and atherosclerosis are characterized by a dysregulation of the pro/anti-inflammatory and Th1/Th2 cytokine balance. Thus, hyperactive or hypoactive stress system, and a dysfunctional neuroendocrine-immune interface associated with abnormalities of the "systemic anti-inflammatory feedback" and/or "hyperactivity" of the local proinflammatory factors may contribute to the pathogenesis of these diseases. Conditions that are associated with significant changes in stress system activity, such as acute or chronic stress, cessation of chronic stress, pregnancy and the postpartum period, or rheumatoid arthritis (RA) through modulation of the systemic or local pro/anti-inflammatory and Th1/Th2 cytokine balance, may suppress or potentiate disease activity and/or progression. Thus, stress hormones-induced inhibition or upregulation of innate and Th cytokine production may represent an important mechanism by which stress affects disease susceptibility, activity, and outcome of various immune-related diseases.
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PMID:Stress system activity, innate and T helper cytokines, and susceptibility to immune-related diseases. 1685 35

Prolylcarboxypeptidase (PRCP) is involved in regulating the blood flow through active tissues in order to preserve the internal environment. The expression of PRCP in tissues is determined by a number of pharmacological stimuli such as glucocorticoids and a combination of dexamethasone plus the mu-opioid receptor agonist [D-Ala2, N-Me-Phe4, Gly5-ol]-Enkephalin acetate. PRCP is an enzyme which is associated with preeclampsia, rheumatoid arthritis, and tonsillitis. The interplay between inward cellular signalling required for induced and basal transcription, and PRCP expression have not been mechanistically characterized. Molecules modulated by PRCP include angiotensin II (Ang II), angiotensin III (Ang III), alpha-MSH, and prekallikrein (PK), demonstrating its cardiovascular protective role. In addition to regulating vascular tone, PRCP may modulate proliferation, cell migration, and angiogenesis through regulating angiotensin molecules--and bradykinin--induced endothelium activation. The anti-hypertensive and proinflammatory properties of PRCP implicate that this enzyme may well be an accessible target for anti-inflammatory therapy.
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PMID:Prolylcarboxypeptidase: a cardioprotective enzyme. 1839 40

Alterations in adrenal steroid production have been suggested in females with rheumatoid arthritis (RA). The aim of the present study was to assess adrenocortical function in RA females. We examined 11 female RA patients (RA: age 30 +/- 2 years, BMI 21.0 +/- 0.7 kg/m(2)) and 10 matched healthy controls (C: age 31 +/- 1 years, BMI 21.6 +/- 0.6 kg/m(2)). Low-dose adrenocorticotropic hormone (ACTH) test (i.v. bolus of 1 microg synthetic ACTH) was performed at 10.00 h with blood sampling every 15 min for 90 min. Cortisol, 17-OH-progesterone (17OHP), androstenedione (ASD), and dehydroepiandrosterone (DHEA) were assayed in plasma. Baseline cortisol levels were higher in RA patients (RA: 385 +/- 38 versus C: 229 +/- 28 nmol/L, P= 0.007). In both study groups, ACTH administration increased all the four steroids measured (P < 0.001). Cortisol response to ACTH administration was diminished in RA patients when compared to controls (Delta(max): 284 +/- 24 in RA versus 424 +/- 31 nmol/L in C, P= 0.002). ACTH-induced maximal rise in plasma DHEA was significantly lower in RA patients when compared to controls (Delta(max): 2.59 +/- 0.68 in RA versus 5.57 +/- 1.25 ng/mL in C, P= 0.015). No significant between-groups differences were found in responses of ASD or 17OHP. The molar ratio of ASD:cortisol was significantly lower (P < 0.05) in RA patients at base line, but did not differ during ACTH test. After ACTH bolus, the cortisol:17OHP ratio decreased significantly in the RA group (P < 0.001), whereas there was no change in the control group. The present results show decreased secretion of cortisol and DHEA in RA patients in response to ACTH, suggesting a subtle HPA hypofunction at the adrenocortical level.
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PMID:Adrenocortical response to low-dose ACTH test in female patients with rheumatoid arthritis. 1912 Jan 58

Patients with rheumatoid arthritis (RA) have significantly lower salivary and serum potassium (K) concentration, reduced total body K, and lower dietary K intake than healthy subjects. There may also be a subtle impairment in the hypothalamic-pituitary-adrenal (HPA) axis in patients with RA with both a poor cortisol secretion response as well as a lower adrenocorticotropin hormone (ACTH) response in relation to involved inflammatory factors. Patients with RA also exhibit an impaired Na+, K+-ATPase (NKA) activity which might promote the pro-inflammatory cytokine secretion seen in RA. I will use these facts to support the mechanism I propose. There are no qualitative differences between the effects of endogenous cortisol and exogenously applied synthetic glucocorticoids (GCs), which are widely used to treat RA. All effects are transmitted via the same receptor. The GC, cortisol, plays a role in normal K homeostasis and the reverse is also seen with higher K intake leading to higher cortisol secretion and biosynthesis. Results of a recent clinical trial showed elevated serum cortisol followed K supplementation. I suggest that this is what alleviated RA symptoms. I would like to suggest a "Cortisol-K" theory as a mechanism for De Coti-Marsh's proposed "K theory" while not precluding the possibility of eventual proof of a cure, possibly from effects of K inside cells other than the adrenal glands.
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PMID:Hypothetical hormonal mechanism by which potassium-rich diets benefit patients with rheumatoid arthritis. 1956 Aug 75


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