Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024141 (systemic lupus erythematosus)
 44,322 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study was designed to determine the prevalence and clinical significance of hyperprolactinemia in systemic lupus erythematosus (SLE) and other rheumatic diseases. Basal levels of prolactin were determined in 130 nonselected sera from patients with rheumatic diseases including 45 with SLE, 31 with rheumatoid arthritis, 23 with osteoarthritis, 18 with fibromyalgia, and 13 with polymyalgia rheumatica. Serum samples of 28 healthy subjects were used as normal controls. Serum prolactin was measured by radioimmunoassay. ANA, anti-DNA, RNP, Sm, Ro, La, and anticardiolipin antibodies were determined by standard techniques. Elevated serum levels of prolactin (PRL greater than 20 ng/ml) were found in a subset of SLE patients. In addition, a direct correlation with clinical disease and serological (ANA) activity was also found. These findings suggest a potential role for this immunoregulatory hormone in SLE pathogenesis.
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PMID:Hyperprolactinemia in systemic lupus erythematosus: association with disease activity. 156 38

This report describes a new method for detecting and quantitating those immunoglobulins G (IgG) in serum that are related to Graves' disease. The method is based on previous observations which indicate that the guinea pig fat cell membrane (FCM) is capable of binding Graves'-specific IgG, but does not bind the IgG common to Graves' disease and Hashimoto's disease, such as antimicrosomal antibodies. Crude FCM preparations were iodinated by a lactoperoxidase technique and were then treated with Triton X-100 to yield a solubilized radioiodinated FCM (SFCM) preparation. SFCM, which retained bovine (b) TSH binding and Graves'-IgG binding properties, provided a radioactively labeled receptor with which to test for the presence of fat cell-binding IgG (FBI) in immunoprecipitates prepared by reacting these IgG with antibody against the Fc fragment of human IgG. FBI values (percentage of added SFCM bound to immunoprecipitate; mean + SD) in IgG from 16 patients with thyrotoxicosis caused by Graves' disease (6.0 +/- 1.7) were completely separated from those in IgG from 16 normal subjects (0.4 +/- 0.3). IgG from 2 hypothyroid patients with Hashimoto's disease, which were strongly positive in the TSH binding inhibition (TBI) assay, yielded FBI values within the range in Graves' disease, but values in TBI-negative IgG from 15 other patients with Hashimoto's disease were normal (0.0 +/- 0.9). Moderately false positive FBI values were found in the IgG of 15 patients with rheumatoid arthritis or systemic lupus erythematosis, all rheumatoid factor positive, 3 of which were also TBI positive. In IgG from Graves' disease and those from patients with TBI-positive collagen-vascular disease, binding of SFCM was inhibited by bTSH in a dose-dependent manner. As with binding of TSH to thyroid plasma membranes, similar but less potent inhibition of binding of IgG to SFCM was produced by LH, FSH, and hCG, but not by insulin, glucagon, PRL, or ACTH. FBI values in TBI-negative IgG from patients with collagen-vascular disease were also decreased by TSH, but higher concentrations of bTSH were required. In 40 IgG from among the various clinical groups tested, a significant correlation was found between FBI values and TBI activity (r = 0.48; P less than 0.01). In addition, among 10 IgG from Graves' disease and 6 from collagen-vascular disease patients, a very close correlation (r = 0.89; P less than 0.001) was noted between their TBI activity and the extent to which their FBI values were decreased by a standard concentration of bTSH.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Detection and measurement of fat cell-binding immunoglobulins: a new method applicable to the diagnosis and study of Graves' disease. 299 73

The frequency of detection of serum antibodies against pituitary cells was determined in 32 patients with the primary empty sella syndrome. Antibodies reacting with corticotropin-secreting mouse AtT20 and PRL-secreting rat GH3 cells were found in 24 (75%) and 15 (47%), respectively, of the 32 patients; 14 patients (44%) had antibodies reacting with both cell lines. In patients with pituitary adenomas, the prevalence of antipituitary antibodies was significantly lower than in those with the empty sella syndrome; 1 of 9 acromegalic patients had antibodies reacting with GH3 cells, and 2 of 9 prolactinoma patients and 1 of 7 patients with nonfunctioning adenomas had antibodies reacting with both AtT20 and GH3 cells. Among 6 patients with idiopathic diabetes insipidus, 1 patient had antibodies reacting with AtT20 and GH3 cells, and 2 patients had antibodies reacting with either AtT20 or GH3 cells. None of 5 patients with established autoimmune diseases (3 with systemic lupus erythematosus and 2 with autoimmune adrenal failure) had antipituitary antibodies in their serum. These results suggest that pituitary antibodies may be related to the development of pituitary atrophy and the primary empty sella syndrome, and that the test may be clinically useful as a screening test for the empty sella syndrome.
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PMID:Antipituitary antibodies in patients with the primary empty sella syndrome. 341 43

We have evaluated the production of PRL by human peripheral mononuclear cells (PBMNC) from normal subjects and patients with systemic lupus erythematosus (SLE). Conditioned medium prepared from basal and Con-A-stimulated PBMNC was assessed for the presence of PRL-like by its ability to stimulate growth of PRL-responsive Nb2 rat lymphoma cells. In the presence or absence of Con-A, SLE PBMNC secrete significantly higher (P < 0.001) amounts of bioactive PRL-like species than normal cells. Growth of Nb2 cells by conditioned medium was inhibited with specific antiserum to human PRL. Western blotting using a polyclonal antibody to human PRL revealed a single 60-kDa PRL-like species in both normal and SLE PBMNC extracts, the immunoreactivity of which was preferentially found in SLE subjects. With the use of reverse transcription-PCR an expected 633-bp band was observed, and its similarity to pituitary PRL was further confirmed by Southern blot analysis with human PRL complementary DNA as a probe. We conclude that a high molecular mass PRL-like species is synthesized and secreted by PBMNC, and patients with SLE have an increased secretion of lymphocyte-derived PRL-like material.
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PMID:A bioactive 60-kilodalton prolactin species is preferentially secreted in cultures of mitogen-stimulated and nonstimulated peripheral blood mononuclear cells from subjects with systemic lupus erythematosus. 936 May 23

PRL is capable of influencing immune responses and is a cytokine in all likelihood. Circulating PRL is elevated in a number of autoimmune diseases, and about 20% of SLE patients are hyperprolactinemic. The serum PRL concentration often does not reflect disease activity in SLE. The PRL-suppressing drug bromocriptine has been reported to benefit small numbers of patients with reactive arthritis and inflammatory eye disease, and bromocriptine may be beneficial in treating SLE. In NZB/NZW mice, bromocriptine was beneficial and prolonged life. Bromocriptine therapy favorably modified disease in human SLE. In a preliminary open-label study, SLE patients treated with bromocriptine for 6 months had significant improvement in disease activity. These responses were corroborated by masted therapeutic studies. Daily treatment with low-dose bromocriptine prevented lupus flares, and bromocriptine was as effective as hydroxychloroquine in treating active nonorgan-threatening disease. The reports of the efficacy of bromocriptine treatment of SLE are encouraging. Additional studies may confirm the findings reported in this review and may lead to further use of hormonal modification to treat lupus and other autoimmune diseases. For the present, it is important to understand that treatment with dopamine agonists such as bromocriptine is experimental and best confined to therapeutic trials. In the experience of the authors, bromocriptine should not be relied on to treat severe life-threatening autoimmune disease. If bromocriptine is used to treat SLE and is then discontinued, the patient should be observed carefully for rebound hyperprolactinemia and the development of a lupus flare. GnRH is produced by lymphocytes and exerts immunomodulatory actions. Thus, GnRH resembles a cytokine. GnRH can be shown to exert gender-restricted immune actions in vitro and in vivo. The authors' preliminary observations are consistent with the possibility that gender-related differences in expression of the GnRH receptor or in GnRH signal transducers may contribute to gender-related differences in immune responsiveness to GnRH. These differences in G proteins may contribute to the gender-related differences in immunity and expression of autoimmune disease.
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PMID:Roles of prolactin and gonadotropin-releasing hormone in rheumatic diseases. 1108 41

A woman with systemic lupus erythematosus (SLE) with marked increases in circulating 150-kDa PRL was studied from before conception, throughout pregnancy, and after pregnancy. The clinical features of the patient included idiopathic hyperprolactinemia without clinical symptoms such as amenorrhea and galactorrhea before pregnancy. No clinical lupus activity was present during follow-up. Serum PRL increase during pregnancy in this patient was considerably higher at weeks 27 and 33 than in normal pregnant women. In contrast, serum-free PRL levels were considerably lower at weeks 20, 27, and 33 than in normal pregnant women. A 150-kDa PRL (big big PRL) species persisted as the predominant circulating form of PRL throughout each measurement in this woman with SLE. In contrast, the predominant form of PRL in serum from healthy pregnant women was little PRL (or monomeric PRL). The nature of big big PRL was due to the presence of anti-PRL autoantibodies forming an IgG-23 kDa PRL complex, in accordance with the studies by affinity chromatography for IgG and Western blot analysis. The IgG-PRL complex was fully bioactive in vitro (Nb2 rat lymphoma cell assay). Injection of the serum into the rats demonstrated that the IgG-PRL complex was cleared more slowly than serum containing predominantly monomeric PRL. The data suggest that the IgG-PRL complex has biological activity; the absence of symptoms in this woman may be attributed to the fact that due to its large molecular weight, big big PRL does not easily cross the capillary walls. Delayed clearance may account for increased serum PRL levels in this SLE patient with anti-PRL autoantibodies.
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PMID:Persistence of macroprolactinemia due to antiprolactin autoantibody before, during, and after pregnancy in a woman with systemic lupus erythematosus. 1139 62

Hyperprolactinaemia is associated with systemic lupus erythematosus (SLE) but the mechanism is unknown. Prolactin is expressed not only by pituitary lactotrophic cells but also by T-lymphocytes under the control of an alternative upstream promoter region. T-lymphocytes from SLE patients have been shown to secrete more prolactin than controls, thus implying a possible underlying difference in regulation. This may be due to genetic polymorphism that can be determined by scanning for mutations and using a variety of methods to determine their function. A polymorphism may also be used in disease association studies as it may be in linkage disequilibrium with a disease gene on the same haplotype. Single nucleotide polymorphisms (SNPs) have been found across the prolactin gene region including the extrapituitary and the pituitary promoter regions. These SNPs have been examined for genetic association with SLE and potential effects upon the function of the gene. One SNP in the lymphocyte specific upstream promoter affects prolactin transcription and disease association studies in a cohort of SLE cases demonstrated an increased frequency of the PRL-1149 G allele compared to control subjects. This indicates a possible mechanism for the association of prolactin with SLE. Although prolactin is likely to be one of several predisposing factors in the pathogenesis and progression of SLE, this suggests that manipulation of lymphocyte prolactin production (rather than pituitary production) might be a useful therapeutic approach.
Lupus 2001
PMID:Polymorphisms of the human prolactin gene--implications for production of lymphocyte prolactin and systemic lupus erythematosus. 1172 93

Within the immune system, multiple isoforms of the human prolactin receptor (PRLr) serve to mediate the effects of its ligand (PRL). Now numbering four, these isoforms are structurally and functionally distinct, demonstrating significant differences in ligand affinities, kinetics of transduction and the transduction proteins activated. The proximal transduction pathways activated during PRLr-associated signaling include the tyrosine kinases Jak2, Fyn and Tec, the phosphatase SHP-2, the guanine nucleotide exchange factor Vav, and the signaling suppressor SOCS. Differential activation of these pathways may contribute to the pleiotropism of PRL action in tissues of the immune system.
Lupus 2001
PMID:Prolactin receptor signal transduction. 1172 97

Monocyte derived macrophages (Mphi) and dendritic cells (DC) play critical roles at the interface between innate and adaptive immunity. Both types of cells can effectively phagocytose exogenous antigens, whereas only DC can process and present them efficiently to antigen-specific T lymphocytes. The hormone PRL is also produced by immune cells and is regarded as a key component of the neuroendocrine--immune loop and a local regulator of lymphocyte response. Its main feature is cooperation with cytokines and hemopoietins. Triggering of monocyte PRL receptors with physiological-to-supraphysiological concentrations of PRL up-regulates the GM-CSF receptors, resulting in synergistic PRL-GM-CSF induced maturation of immature (i)DC. Further incubation induces increased antigen-presenting activity at the highest PRL concentrations studied (200 ng/ml). IFN-gamma, release by allogeneic lymphocytes is dependent on T cell-triggered IL-12 release by PRL-preincubated iDC. This, in turn, may be secondary to increased DC expression of CD40 or IFN-gamma. The permissive action of high PRL concentrations in the antigen presenting process may be of significance in initiation of the response against major histocompatibility complex (MHC)-presented self-antigens and may explain the association of hyperprolactinemia with autoimmune diseases.
Lupus 2001
PMID:Effect of prolactin on the antigen presenting function of monocyte-derived dendritic cells. 1172 99

Receptors for prolactin (PRL-R) are expressed in normal leukocytes from rat and man. PRL signals through PRL-R associated Janus tyrosine kinase (Jak)-2 and signal transducers and activators of transcription (Stat). In addition, in human leukocytes PRL also activates the p38 MAP kinase pathway. PRL, at physiological concentrations, stimulates the expression of the interferon regulatory factor (IRF)-1 gene in rat spleen and bone marrow cells. In man, genes induced by PRL include several members of the 'suppressors of cytokine signaling' (SOCS) family and inducible nitric oxide synthase (iNOS; in mononuclear cells and in granulocytes) and IRF-1 (in granulocytes). Thus, in normal leukocytes, PRL induces the expression of several genes relevant to innate and acquired immune responses. Sex hormones, such as estrogen and PRL, have been implicated in the pathogenesis of murine and human SLE. Also defective signaling in leukocytes is a feature of the disease. What the origin is of aberrant signaling processes in SLE lymphocytes and how they relate to tolerance breakdown and immunopathology is still unknown. It is not unlikely that PRL is a player at some level. The exact contribution of PRL to immune responses in normal subjects and in SLE patients is not known. Further work should also indicate whether PRL might contribute to the onset or progression of the disease and assess the possible benefits of manipulating PRL concentrations in patients.
Lupus 2001
PMID:Effects of prolactin on signal transduction and gene expression: possible relevance for systemic lupus erythematosus. 1172 98


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