Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0409974 (lupus)
 22,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Prolactin in a pituitary peptide hormone which is immunomodulatory. Increased serum prolactin concentrations accelerate autoimmunity in the NZB x NZW F1 mouse model of SLE. Some patients with SLE are hyperprolactinemic and, in cross-sectional and longitudinal studies, serum prolactin has been associated with or correlated to lupus disease activity. Suppression of physiologic levels of prolactin by bromocriptine administration was associated with improvement in SLE in a preliminary study. While specific mechanisms remain to be elucidated, prolactin appears to be immunostimulatory in patients with SLE. A better understanding of its role and its interactions with other immunoregulatory hormones in SLE may lead to novel therapies for the suppression of this hormonally sensitive autoimmune disease.
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PMID:Prolactin and systemic lupus erythematosus. 895 44

Prolactin (PRL) is an important immunoregulatory hormone secreted by the anterior pituitary gland. Hyperprolactinaemia has been implicated in the pathogenesis of systemic lupus erythematosus (SLE). However, clinical studies regarding the PRL level and lupus disease activity have yielded contradictory results. The aim of our present study was, therefore, to re-evaluate the association of PRL level and disease activity in SLE by analysing a larger patient cohort and following them up serially. Seventy-two consecutive SLE patients were recruited and the serum PRL level was measured at each visit. Our results showed that hyperprolactinaemia (> 500 mIU/l) occurred in 35% (25/72) of the patients. A total of 72% (18/25) of the hyperprolactinaemic patients had mild elevation (arbitrarily defined as 500-800 mIU/l) of the level only. No correlation could be found between the PRL level and various clinical and serological parameters of lupus disease activity. On serial follow-up of 44 patients, again no correlation between PRL and disease activity could be demonstrated. We conclude that hyperprolactinaemia occurs in some patients with SLE, but the serum level of PRL does not correlate with clinical or serological disease activity and is not a reliable marker for disease monitoring. The mechanism and pathoaetiological and clinical significance of hyperprolactinaemia in a small subset of SLE patients remain unclear and a longer follow-up is necessary.
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PMID:Prolactin profile in a cohort of Chinese systemic lupus erythematosus patients. 978 73

Prolactin (PRL) is closely associated with autoimmune diseases in animal models and humans, and several disease-related autoantibodies were reported in increased titers in patients with hyperprolactinemia (HPRL). We studied the presence of anti-endothelial cell antibodies (AECA) and other autoantibodies in sera of female patients with HPRL. Sera from 25 HPRL patients and 10 healthy female controls were tested for AECA (against both macrovascular and microvascular endothelial cell antigens), anti-dsDNA, and anti-cardiolipin (anti-CL) using ELISA. Sera were considered positive for the autoantibody when the optical density (OD) value was more than 3 s.d. above the mean of the OD in normal controls. Sera from 13 patients were obtained repeatedly during dopaminergic anti-PRL treatment, to relate PRL level or anti-PRL treatment with the autoantibody levels. Elevated micro and/or macrovascular AECA were observed in sera from 19/25 patients (76%). Elevated titers of anti-CL Abs, all beta2-GPI-dependent, and low levels of anti-dsDNA antibodies (Abs) were also observed in the HPRL patients. Inhibition studies showed that the affinity purified AECAs bound the endothelial cell (EC) antigens in a dose-dependent manner. Titers of AECA as well as anti-DNA and anti-CL autoantibodies did not correlate with PRL level nor with the use or duration of anti-PRL treatment. None of the HPRL patients presented clinical manifestations of autoimmune disease. We conclude that elevated levels of AECA as well as anti-DNA and anti-CL autoantibodies are frequent in hyperprolactinemia. Our results further support the association of PRL and autoimmunity, and may point to a relationship between AECA-associated diseases and HRPL. The presence of autoantibodies in patients with HPRL might portend an increased risk for future development of autoimmune disease.
Lupus 1998
PMID:Anti-endothelial cell antibodies in the sera of hyperprolactinemic women. 973 19

Prolactin (PRL) is an important immunoregulator and might have a role in the pathogenesis of systemic lupus erythematosus (SLE). The regulation of pituitary prolactin secretion is complex and involves a negative feedback process in the hypothalamus, in which dopamine plays the principal role. However, the main source of serum prolactin in lupus patients is still not clearly established. Since homovanillic acid (HVA), the principal metabolite of dopamine (DA), is removed from the brain into the blood, it would indirectly reflect DA metabolism. It is assumed that the turnover of a neurotransmitter can be determined through an analysis of its metabolites. The objective of this study was to analyse plasma samples from SLE patients to see if there were any alterations in neurally functioning DA through its principal metabolite, HVA. We also measured the levels of PRL and compared HVA and PRL with the clinical activity of the disease. Twenty-four SLE patients and fifteen healthy controls were studied. The investigation was done over a period of 3 months. The results of this study show significantly low levels of HVA in lupus patients compared to controls (P < 0.0001). This corresponds to a decrease in dopamine turnover. Hyperprolactinemia was observed in nine patients, and the average level of prolactin in lupus patients was higher than in healthy controls (P < 0.001). For the duration of the study, a significant percentage of variation was observed in the levels of HVA in the clinically active patients (P < 0.05) compared to inactive patients. When PRL was compared in these groups, throughout the study, no significant percentage of variation was observed. The relationship between HVA and PRL in healthy controls was r = 0.47, P = 0.08, and in patients was r = 0.04, P = 0.84. It is suggested that there is a probable association between plasma levels of HVA and PRL in the healthy controls and not in the SLE patients.
Lupus 1998
PMID:Plasma homovanillic acid and prolactin in systemic lupus erythematosus. 973 22

Prolactin, a lactogenic hormone, is a cytokine and an important link between the immune and endocrine systems. Prolactin stimulated disease in autoimmune NZB/NZW mice. Treatment of the mice with the prolactin-lowering dopamine agonist, bromocriptine, suppressed anti-DNA and prolonged life spans. These findings have been applied to humans with systemic lupus erythematosus (SLE). An open-label study, a double blind study, and a study comparing bromocriptine to hydroxychloroquine provided evidence that bromocriptine therapy reduced flares and suppressed disease activity in SLE.
Lupus 2001
PMID:Treatment of systemic lupus erythematosus with bromocriptine. 1131 52

Estrogen and prolactin have a reciprocal endocrinologic relationship and both hormones have pleiotropic effects on the immune system. Despite the presence of a number of confounding variables, these hormones modulate autoimmunity; however, mechanisms by which this modulation occurs remain obscure. Estrogen appears to suppress cell-mediated and augment humoral-based immunity. Prolactin appears to stimulate both cell and humoral-based immunity. Both hormones have been shown to modulate IFN gamma secretion. Similar evidence in experimental models, human autoimmune disease, and during pregnancy in autoimmune disease patients suggests disparate effects of estrogen and prolactin on autoimmune responses and disease pathogenesis. In the NZB x NZW F1 mouse model of lupus, prolactin accelerates disease expression, whereas estrogen, devoid of its prolactin stimulating properties, is immunosuppressive and inhibits IL-2 production. Estrogen, because of its endocrinologic and immune effects, may directly or indirectly stimulate or inhibit immune responses. These dichotomous effects have limited its successful pharmacologic manipulation in human autoimmune disease with estrogen compounds, tamoxifen, oral contraceptives, antigonadotropic agents, or ovulation induction regimens. In contrast, reduction of immunostimulatory concentrations of prolactin with bromocriptine has successfully suppressed development or expression of murine and human autoimmune disease. Further investigation into actions and interactions of estrogen and prolactin with autoimmunity will provide a better understanding of the female preponderance of autoimmunity and facilitate a more rational approach to hormonal immunotherapy.
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PMID:Estrogen, prolactin, and autoimmunity: actions and interactions. 1140 18

Prolactin (PRL) is a pituitary hormone and a cytokine that plays an important role in rodent and human immune responses, including autoimmune diseases. However, many cells and tissues other than the pituitary make PRL, including immune cells. Here, we will present the evidence demonstrating PRL synthesis by different subtypes of immune cells from humans, mice and rats, describe the regulation of PRL gene expression in human lymphocytes, and discuss the functions of PRL made by immune cells. Finally, we will present evidence for involvement of immune cell PRL in human autoimmune disease and suggest how it might play a unique immunoregulatory role.
Lupus 2001
PMID:Prolactin production by immune cells. 1172 92

Prolactin secretion from the anterior pituitary is mediated via dopaminergic pathways. Any process that alters dopamine production or transport in the central nervous system may lead to hyperprolactinemia. Most cases of hyperprolactinemia are due to prolactin secreting pituitary tumors or to medications which alter dopamine production. Prolactinomas cause amenorrhea, galactorrhea and infertility in women and impotence and neurological deficits in men. Dopamine receptor agonists are the mainstay of therapy for hyperprolactinemia as they rapidly lower serum prolactin and cause tumor shrinkage. In this paper we review the regulation of prolactin secretion, the clinical features and causes of hyperprolactinemia, and the use of dopamine agonists.
Lupus 2001
PMID:Pituitary production of prolactin and prolactin-suppressing drugs. 1172 91

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

Prolactin (PRL), a pituitary peptide hormone, is known to regulate diverse cellular functions including proliferation, differentiation, angiogenesis and protection against apoptosis and inflammation. To understand the mechanism of PRL signaling in T cells, we have cloned both PRL and its receptor (PRL-R), one potent mediator of PRL signaling, Stat5b, and a panel of PRL-inducible immediate early genes from T cells. We are employing these genes as tools with which to understand how PRL regulates the expression of one target gene, the transcription factor interferon regulatory factor-1 (IRF-1), which is a multifunctional immune regulator gene. In investigating regulatory events along the PRL-R/JAK/Stat/IRF-1 signaling pathway, we show that Stat factors can activate as well as inhibit IRF-1 promoter activity and that cross-talk between Stat and NFkappaB signaling pathways also regulates IRF-1 promoter activity. These findings have much broader implications not only for T lymphocytes but also for other PRL responsive target cells and tissues.
Lupus 2001
PMID:Stimulation of interferon regulatory factor-1 by prolactin. 1172 95


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