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Over 100 diseases have been recognized as autoimmune in nature, collectively affecting ∼20 % of the population in industrialized countries. These conditions are more prevalent among women of childbearing age, reflecting the potential association between alterations in the immune-neuroendocrine network, on the one hand, and autoimmune conditions, on the other. Prolactin (PRL), a polypeptide hormone that is primarily (but not only) secreted by the lactotrophic cells of the pituitary gland, is a critical element of the immune-neuroendocrine network. Although this hormone has several nonimmune functions, its role in regulating immune responses and affecting autoimmune inflammation is particularly enigmatic and controversial. Indeed, PRL interacts with various immune cells to bolster the body defenses, but also potentially to exacerbate autoimmune conditions. Understanding how and when PRL acts as a 'friend or foe' is crucial for unraveling its role as a potential therapeutic target in the management of autoimmune diseases (AIDs). This review therefore provides a critical overview of PRL's role in the immune system, and of the influence of this pleiotropic hormone in the development of autoimmunity., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Background: Prolactin (Prl) is a pleiotropic hormone initially described for its regulation of lactation in mammals but later associated with metabolic and immune homeostasis, stress, inflammatory response and human behavior. Its regulation through dopamine receptors highlights its importance in psychiatry mostly because hyperprolactinemia is a common secondary side effect of dopamine antagonists. Despite its undeciphered patho-physiological mechanisms, hyperprolactinemia in naïve psychosis patients has been widely described. Its consequences might underlie the increased morbidity and early mortality found in naïve subjects as described in the general population where prolactin values have been correlated with inflammatory, immune and metabolic parameters., Methods: We aimed to evaluate the correlation between prolactin values and other biochemical parameters (C-reactive Protein-CrP, blood cell count, lipid and hepatic profile, fasting glucose) in a cohort of first episode psychosis naïve subjects (N = 491) stratified by sex. Regression analyses with confounders were performed to evaluate the association., Findings: Prl displayed significant correlations with C-Reactive Protein (CrP), Low-Density Lipoprotein (LDL), Aspartate Transaminase (AST) for females and High-Density Lipoprotein (HDL) and eosinophil count for males. However, and despite previous specific sex correlations, significant associations were described for CrP, HDL, LDL, AST and ALT without sex interaction and despite confounders such as age, Body Mass Index or smoking status., Conclusions: Our results show a specific relation of Prl with immune and metabolic parameters describing a heterogeneous pattern. Our results suggest that prolactin might underlie the excess of morbidity and early mortality in naïve patients through a specific pathway., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Similar to other immune-mediated diseases, IgG4-related disease (IgG4-RD) is the disease that develops in genetically susceptible individuals exposed to external or endogenous antigens. In the present study, it was confirmed that MAG (myelin-associated glycoprotein) antibodies (IgG, IgG4, and IgM) were detected by immunofluorescence (IFA) in serum of the patients with IgG4-RD. In vivo, the levels of prolactin and Th2 cytokines in CGRP +/- rats were higher than those in wild-type. Our findings indicate that the presence of CGRP-deficiency-mediated MAG antibodies is a probable molecular basis for the initial events which were triggered in IgG4-RD immune responses via prolactin upregulation.

Background: Macroprolactin mostly composed of an immunoglobulin G (IgG) and a monomeric prolactin (PRL) represents the major circulating PRL form in the patients with macroprolactinemia that are usually asymptomatic and may not require treatment. In this study, we aimed to evaluate the prevalence of antithyroid and antinuclear antibodies, as well as the IgG subclass distributions in the patients suspected for macroprolactinemia., Methods: From January to July in 2018, totally 317 patients with elevated PRL were subjected to the polyethylene glycol (PEG) precipitation assay. The patients with recovery rates of ≤60% were subjected for IgG subclass determination and autoantibody testing including thyroid peroxidase antibody (aTPO), antithyroglobulin antibody (aTG), and antinuclear antibodies (ANA)., Results: The higher the post-PEG PRL recovery rates, the less typical hyperprolactinemia symptoms and the higher prevalence of autoantibodies were observed. The IgG1 and IgG3 were the predominant subclasses in the PRL-IgG complexes according to the immunoprecipitation experiments., Conclusion: The patients with post-PEG PRL recovery rates of <40% and 40%-60% were likely to represent two distinct populations of different clinical presentations. The prevalence of autoantibodies and IgG subclasses distribution suggested their pathogenic significance in the development of macroprolactinemia., (© 2020 The Authors. Journal of Clinical Laboratory Analysis Published by Wiley Periodicals LLC.)

Prolactin (PRL), the well-known lactogenic hormone, plays a crucial role in immune function given the fact that long term hypoprolactinemia (serum prolactin level below normal) can even lead to death from opportunistic infection. High blood PRL level is known to provide an immunological advantage in many pathological conditions (with some exceptions like autoimmune diseases) and women, because of their higher blood PRL level, get an advantage in this regard. It has been reported that by controlled enhancement of blood PRL level (within the physiological limit and in some cases a little elevated above the normal to induce mild hyperprolactinemia) using dopamine antagonists such immune-stimulatory advantage can led to survival of the patients in many critical conditions. Here it is hypothesized that through controlled augmentation of blood PRL level using dopamine antagonists like domperidone/metoclopramide, which are commonly used drugs for the treatment of nausea and vomiting, both innate and adaptive immunity can be boosted to evade or tone down COVID-19. The hypothesis is strengthened from the fact that at least seven little-understood salient observations in coronavirus patients can apparently be explained by considering the role of enhanced PRL in line with the proposed hypothesis and hence, clinical trials (both therapeutic and prophylactic) on the role of enhanced PRL on the course and outcome of coronavirus patients should be conducted accordingly., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Hormones are known to influence various body systems that include skeletal, cardiac, digestive, excretory, and immune systems. Emerging investigations suggest the key role played by secretions of endocrine glands in immune cell differentiation, proliferation, activation, and memory attributes of the immune system. The link between steroid hormones such as glucocorticoids and inflammation is widely known. However, the role of peptide hormones and amino acid derivatives such as growth and thyroid hormones, prolactin, dopamine, and thymopoietin in regulating the functioning of the immune system remains unclear. Here, we reviewed the findings pertinent to the functional role of hormone-immune interactions in health and disease and proposed perspective directions for translational research in the field., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Induction of eomesodermin-positive CD4 + T cells (Eomes + T helper [Th] cells) has recently been correlated with the transition from an acute stage to a later stage of experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis. Moreover, these cells' pathogenic role has been experimentally proven in EAE. While exploring how the pathogenic Eomes + Th cells are generated during the course of EAE, we unexpectedly found that B cells and MHC class II + myeloid cells isolated from the late EAE lesions strikingly up-regulated the expression of prolactin (PRL). We demonstrate that such PRL-producing cells have a unique potential to induce Eomes + Th cells from naïve T cells ex vivo, and that anti-MHC class II antibody could block this process. Furthermore, PRL levels in the cerebrospinal fluid were significantly increased in the late phase of EAE, and blocking the production of PRL by bromocriptine or Zbtb20-specific siRNA significantly reduced the numbers of Eomes + Th cells in the central nervous system (CNS) and ameliorated clinical signs in the later phase of EAE. The PRL dependency of Eomes + Th cells was confirmed in a series of in vitro and ex vivo experiments. Collectively, these results indicate that extrapituitary PRL plays a crucial role in the CNS inflammation mediated by pathogenic Eomes + Th cells. Cellular interactions involving PRL-producing immune cells could be considered as a therapeutic target for the prevention of chronic neuroinflammation., Competing Interests: The authors declare no conflict of interest., (Copyright © 2019 the Author(s). Published by PNAS.)

The aim of this study was to determine the cellular and molecular mechanisms of prolactin (PRL) in testicular development of prepubertal cockerels. In an in vivo animal experiment, active immunization against PRL severely depressed prepubertal testicular development by significantly reducing testicular weights at both 122 and 164 d of age. The number of elongated spermatids in the seminiferous tubules was also significantly decreased by immunization with 199-residue chicken PRL (cPRL) at age 122 d. Inhibition of testicular development by cPRL immunization was associated with decreases in LH receptor (LHR), FSH receptor (FSHR), Stat5b, P450scc, steroidogenic acute regulatory (StAR) protein, and 3β-hydroxysteroid dehydrogenase (3β-HSD) mRNA expression levels in testicular tissue. In in vitro experiments, testosterone production by cultured Leydig cells isolated from prepubertal cockerel testes was dose-dependently enhanced by treatment with bioactive recombinant PRL, but a lesser response was seen with high concentrations of PRL. The distinct changes in testosterone production in response to high and low concentrations of added PRL were paralleled by similar patterns of change in the mRNA levels of Stat5b, LHR, P450scc, StAR, 3β-HSD, and CYP17A1 in cultured Leydig cells, as well as protein amounts of phosphorylated Jak2 and Stat5a/b. In conclusion, low to medium doses of PRL potentiate testis development in prepubertal cockerels by enhancing testosterone secretion from Leydig cells via activation of PRLR/Stat5b signal transduction, which upregulates mRNA expression of LHR and testosterone synthesizing enzymes. However, this positive regulation was weaker in response to a high dose of PRL, which reduced PRLR/Stat5b signal transduction and the expression of genes involved in LH signaling and testosterone synthesis., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Increasing systemic prolactin levels improves remyelination and neuronal survival in animal models of Multiple Sclerosis (MS), but it has been suggested that this therapeutic strategy may also increase inflammatory responses, and potentially harm patients. We analyzed serum prolactin and cytokine, chemokine and growth factor levels in sera from MS patients enrolled in two clinical trials who were treated with domperidone, a generic drug that increases systemic prolactin levels. In patients treated with domperidone, molecule levels changed little during follow up, while prolactin levels increased several-fold. We found no significant association between prolactin levels and radiological or clinical outcome., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The present study was conducted to establish a sandwich ELISA for the determination of prolactin (PRL) concentrations in the plasma of domestic fowls. The assay uses a recombinant goose PRL as the reference standard, expressed in a eukaryotic system, and as the antigen for raising a polyclonal antibody in rabbit. This rabbit anti-goose PRL polyclonal antibody was used for coating the wells of the ELISA plate, and its biotinylated form served as the detection antibody. An avidin-conjugated horseradish peroxidase was used to bind the detection antibody and to catalyze the chromogenic reaction using 3,3',5,5'-tetramethylbenzidine as the substrate. The assay showed a linear relationship between the optical density and concentration of the standard PRL in the 0 to 12.5 ng/mL range, and the assay was sensitive to a concentration as low as 0.39 ng/mL. The intra- and inter-assay CVs were <7% and 11%, respectively. The response curves of the serially diluted plasma samples from goose, duck, and chicken exhibited similar parallel relationships to that observed for the reference standards. Consistent with previous findings, the assay effectively detected differences in PRL concentration in plasma samples from chicken, duck, and goose at various reproductive stages., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Although it is well-recognized that inflammation enhances leukocyte bactericidal activity, the underlying mechanisms are not clear. Here we report that PRL2 is sensitive to oxidative stress at inflamed sites. Reduced PRL2 in phagocytes causes increased respiratory burst activity and enhances phagocyte bactericidal activity. PRL2 (Phosphatase Regenerating Liver 2) is highly expressed in resting immune cells, but is markedly downregulated by inflammation. in vitro experiments showed that PRL2 was sensitive to hydrogen peroxide (H 2 O 2 ), a common damage signal at inflamed sites. In response to infection, PRL2 knockout (KO) phagocytes were hyper activated, produced more reactive oxygen species (ROS) and exhibited enhanced bactericidal activity. Mice with PRL2 deficiency in the myeloid cell compartment were resistant to lethal listeria infection and cleared the bacteria more rapidly and effectively. Moreover, in vitro experiments demonstrated that PRL2 binds to GTPase Rac and regulates ROS production. Rac GTPases were more active in PRL2 (KO) phagocytes than in wild type cells after bacterium infection. Our findings indicate that PRL2 senses ROS at inflamed sites and regulates ROS production in phagocytes. This positive feedback mechanism promotes bactericidal activity of phagocytes and may play an important role in innate anti-bacterial immunity.

The fabrication of a novel electrochemical immunosensor for rapid and precise determination of prolactin was carried out using carbon paste electrode (CPE) consist of ionic liquid (IL) and graphite. Gold nanoparticles were employed as a modifier on the surface of CPE to immobilize the prolactin antibody (anti-PRL). The immunoassay was set up by sandwiching the antigen between prolactin antibody and the polyclonal anti-human-prolactin antibody labeled with horseradish peroxidase (HRP-labeled anti-PRL) as secondary antibody, on the surface of modified CPE. The reaction between O-aminophenol (OAP) and H 2 O 2 which is catalyzed by labeled HRP on the sandwich immunosensor generate a signal in differential pulse voltammetry (DPV) that is used to determine the concentration of prolactin. This immunosensor provides the measurement of prolactin concentration in a linear range of 25.0-2000.0 mIU L -1 with a detection limit 12.5 mIU L -1 . Moreover, it is applicable in the clinical assay of prolactin due to its high sensitivity and acceptable stability., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Toxocariasis is a zoonotic disease produced by ingestion of larval Toxocara spp. eggs. Prolactin (PRL) has been considered to have an important role in Toxocara canis infection. Recent evidence has found that PRL directly can increase parasite growth and differentiation of T. canis The present study, evaluated the effect of high PRL levels on the immune system's response and parasites clearance in chronic infection. Our results showed that hyperprolactinemia did not affect the number of larvae recovered from several tissues in rats. Parasite-specific antibody production, showed no difference between the groups. Lung tissue presented eosinophilic granulomas typical of a chronic infection in all the experimental groups. Flow cytometry analysis was made in order to determine changes in the percentage of innate and adaptive immune cell subpopulations in the spleen, peripheric (PLN) and mesenteric (MLN) lymphatic nodes. The results showed a differential effect of PRL and infection on different immune compartments in the percent of total T cells, T helper cells, T cytotoxic cells, B cells, NK cells, and Tγδ cells. To our knowledge, for the first time it is demonstrated that PRL can have an immunomodulatory role during T. canis chronic infection in the murine host., (© 2018 The Author(s).)

Background: Hyperprolactinemia diagnosis and treatment is often compromised by the presence of biologically inactive and clinically irrelevant higher-molecular-weight complexes of prolactin, macroprolactin. The objective of this study was to evaluate the performance of two macroprolactin screening regimes across commonly used automated immunoassay platforms., Methods: Parametric total and monomeric gender-specific reference intervals were determined for six immunoassay methods using female (n=96) and male sera (n=127) from healthy donors. The reference intervals were validated using 27 hyperprolactinemic and macroprolactinemic sera, whose presence of monomeric and macroforms of prolactin were determined using gel filtration chromatography (GFC)., Results: Normative data for six prolactin assays included the range of values (2.5th-97.5th percentiles). Validation sera (hyperprolactinemic and macroprolactinemic; n=27) showed higher discordant classification [mean=2.8; 95% confidence interval (CI) 1.2-4.4] for the monomer reference interval method compared to the post-polyethylene glycol (PEG) recovery cutoff method (mean=1.8; 95% CI 0.8-2.8). The two monomer/macroprolactin discrimination methods did not differ significantly (p=0.089). Among macroprolactinemic sera evaluated by both discrimination methods, the Cobas and Architect/Kryptor prolactin assays showed the lowest and the highest number of misclassifications, respectively., Conclusions: Current automated immunoassays for prolactin testing require macroprolactin screening methods based on PEG precipitation in order to discriminate truly from falsely elevated serum prolactin. While the recovery cutoff and monomeric reference interval macroprolactin screening methods demonstrate similar discriminative ability, the latter method also provides the clinician with an easy interpretable monomeric prolactin concentration along with a monomeric reference interval.

Prolactin (PRL) is a neuroendocrine hormone that can promote inflammation. We examined the synovial tissue and fluid levels of PRL in patients with inflammatory arthritis, PRL expression in differentiated Mϕs from patients with arthritis and from healthy donors, and the effects of different stimuli on PRL production by Mϕs. PRL levels were measured in paired synovial fluid (SF) and peripheral blood of patients with rheumatoid arthritis (RA, n = 19), psoriatic arthritis (PsA, n = 11), and gout ( n = 11). Synovial-tissue PRL mRNA expression was measured by quantitative PCR in patients with RA ( n = 25), PsA ( n = 11), and gout ( n = 12) and in Mϕs differentiated in SF of patients with RA, PsA, other subtypes of spondyloarthritis (SpA), and gout. Synovial-tissue PRL mRNA expression correlated significantly with clinical disease parameters in patients with RA and PsA, including erythrocyte sedimentation rate (ESR, r = 0.424; P = 0.049) and disease activity score evaluated in 28 joints (DAS28, r = 0.729; P = 0.017). Synovial-tissue PRL expression was similar in RA, PsA, and gout. PRL mRNA expression was detected in monocyte-derived Mϕs from patients with RA and was significantly higher ( P ≤ 0.01) in Mϕs differentiated in pooled SF from patients with RA and PsA compared with SpA or gout. PRL production by Mϕ differentiation in the SF from patients with RA was not further regulated by stimulation with CD40L, IgG, LPS, or TNF. PRL is produced locally in the synovium of patients with inflammatory arthritis. The production of PRL by Mϕs was increased by unknown components of RA and PsA SF, where it could contribute to disease progression., (© Society for Leukocyte Biology.)

Over the past decades, a number of prolactin receptor (PRLR) antagonists have been developed, which can be divided into two categories, PRLR analogue and anti-PRLR antibody. However, until now, there have been no commercially available PRLR antagonists. Here, we described a new approach for the preparation of PRLR antagonist, namely internal image anti-idiotypic antibody strategy. The hybridoma technique was used to generate anti-idiotypic antibodies to PRL. Competitive ELISA, competitive receptor-binding analysis and immunofluorescence assay (IFA) were then used to screen and characterize anti-idiotypic antibodies to PRL. One internal image anti-idiotypic antibody, termed MG7, was obtained. A series of experiments demonstrated that MG7 behaved as a typical internal image anti-idiotypic antibody (Ab2β). MG7 exhibited effective antagonistic activity, which not only inhibited PRL binding to PRLR in a dose-dependent manner but also inhibited PRLR-mediated intracellular signalling. Furthermore, MG7 also blocked Nb2 cell proliferation induced by PRL. The current study suggests that MG7 has the potential application in the PRL/PRLR-related studies in future. In addition, this work also suggests that the internal image anti-idiotypic antibody may represent a novel strategy for the development of PRLR antagonist., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Prolactin, a 23-kDa peptide hormone, is produced by the anterior pituitary gland and extrapituitary sites including the immune cells. Prolactin (PRL) participates in innate and adaptive immune response. PRL stimulates the immune cells by binding to receptor (PRL-R). Binding of PRL to its receptor activates the Janus kinase-signal transducer (JAK-STAT). Activation of these cascades results in endpoints such as immunoestimulator and immunosupressor action. Prolactin belongs to the network of immune-neuroendocrine interaction. Hyperprolactinemia has been found in patients with systemic lupus erythematosus (SLE), and new evidence has confirmed a significant correlation between serum PRL levels and disease activity. PRL participates in activation of SLE during pregnancy and in pathogenesis of lupus nephritis, neuropsychiatric, serosal, hematologic, articular, and cutaneous involvement. Hyperprolactinemia was associated with increase IgG concentrations, anti-DNA antibodies, immune complex, glomerulonephritis, and accelerated mortality in murine lupus. Bromocriptine, a dopamine analog that suppresses PRL secretion, was associated with decreased lupus activity, prolonged lifespan, and restoration of immune competence in experimental model. In clinical trials, bromocriptine and derivative drugs showed beneficial therapeutic effect in treating human lupus, including pregnancy. Taken together, clinical and experimental results leave little doubt that PRL indeed contributes to the pathogenesis and clinical expression of SLE.

The review provides information about the features of the sensitivity of thymocytes, lymphoid organs' cells and T-lymphocytes of peripheral blood to the hormones secreted by anterior pituitary gland's cells: growth hormone, thyrotropin, adrenocorticotropic hormone, prolactin and β-endorphin. Some aspects of the T-lymphocytes's response to humoral signals from the hypophysis are shown in the article. Also the pituitary hormones' role in the regulation of proliferation, differentiation, and cytokine production of T-lymphocytes in normal and pathological conditions of the organism being discussed.

Rheumatoid arthritis (RA) is a chronic, autoimmune, inflammatory disease destroying articular cartilage and bone. The female preponderance and the influence of reproductive states in RA have long linked this disease to sexually dimorphic, reproductive hormones such as prolactin (PRL). PRL has immune-enhancing properties and increases in the circulation of some patients with RA. However, PRL also suppresses the immune system, stimulates the formation and survival of joint tissues, acquires antiangiogenic properties upon its cleavage to vasoinhibins, and protects against joint destruction and inflammation in the adjuvant-induced model of RA. This review addresses risk factors for RA linked to PRL, the effects of PRL and vasoinhibins on joint tissues, blood vessels, and immune cells, and the clinical and experimental data associating PRL with RA. This information provides important insights into the pathophysiology of RA and highlights protective actions of the PRL/vasoinhibin axis that could lead to therapeutic benefits.

Background: Macroprolactinaemia is a major cause of hyperprolactinaemia. The detectability of macroprolactin varies widely among different immunoassay systems, but the causes are not fully known. This study aimed to identify the factors influencing the detectability of macroprolactin by immunoassay systems., Methods: The study included 1544 patients who visited an obstetric and gynaecological hospital. Macroprolactinaemia was screened using the polyethylene glycol (PEG) method and confirmed using gel filtration chromatography and the protein G method. The prolactin (PRL) values determined by enzyme immunoassay (EIA) were compared with those of a chemiluminescence immunoassay system (Centaur) that is known to cross-react the least with macroprolactin., Results: Macroprolactinaemia was found in 62 of 1544 patients (4.02%) who visited an obstetric and gynaecological hospital. The ratio of EIA-determined total PRL to free PRL in the supernatant after PEG precipitation was significantly elevated in all 62 serum samples with macroprolactin compared to those in 1482 serum samples without macroprolactin. In contrast, the ratio of Centaur-determined total PRL to free PRL was significantly elevated in 32 serum samples (group 1) and was within the normal range in 30 (group 2) of 62 serum samples with macroprolactin. The prevalence of non-IgG-type macroprolactin was significantly higher in group 1 than in group 2. Centaur diagnosed hyperprolactinaemia less frequently than EIA (n=2 vs. 16) in 62 patients with macroprolactinaemia. Those two hyperprolactinaemic patients diagnosed by Centaur had non-IgG-type macroprolactin., Conclusions: Macroprolactinaemia was present in 4% of patients visiting an obstetric and gynaecological hospital. The nature of macroprolactin (IgG-type or non-IgG-type) may partly explain why macroprolactin detectability varies among different immunoassay systems.

The physiology of the thymus, the primary lymphoid organ in which T cells are generated, is controlled by hormones. Data from animal models indicate that several peptide and nonpeptide hormones act pleiotropically within the thymus to modulate the proliferation, differentiation, migration and death by apoptosis of developing thymocytes. For example, growth hormone and prolactin can enhance thymocyte proliferation and migration, whereas glucocorticoids lead to the apoptosis of these developing cells. The thymus undergoes progressive age-dependent atrophy with a loss of cells being generated and exported, therefore, hormone-based therapies are being developed as an alternative strategy to rejuvenate the organ, as well as to augment thymocyte proliferation and the export of mature T cells to peripheral lymphoid organs. Some hormones (such as growth hormone and progonadoliberin-1) are also being used as therapeutic agents to treat immunodeficiency disorders associated with thymic atrophy, such as HIV infection. In this Review, we discuss the accumulating data that shows the thymus gland is under complex and multifaceted hormonal control that affects the process of T-cell development in health and disease.

Ames hypopituitary dwarf mice are deficient in growth hormone, thyroid-stimulating hormone, and prolactin. The phenotype of these mice demonstrates irregularities in the immune system with skewing of the normal cytokine milieu towards a more anti-inflammatory environment. However, the hematopoietic stem and progenitor cell composition of the bone marrow (BM) and spleen in Ames dwarf mice has not been well characterized. We found that there was a significant decrease in overall cell count when comparing the BM and spleen of 4-5 month old dwarf mice to their littermate controls. Upon adjusting counts to differences in body weight between the dwarf and control mice, the number of granulocyte-macrophage progenitors, confirmed by immunophenotyping and colony-formation assay was increased in the BM. In contrast, the numbers of all myeloid progenitor populations in the spleen were greatly reduced, as confirmed by colony-formation assays. This suggests that there is a shift of myelopoiesis from the spleen to the BM of Ames dwarf mice; however, this shift does not appear to involve erythropoiesis. The reasons for this unusual shift in spleen to marrow hematopoiesis in Ames dwarf mice are yet to be determined but may relate to the decreased hormone levels in these mice., (Copyright © 2015. Published by Elsevier Inc.)

Prolactin (PRL) has long been proposed as an immune-stimulating and detrimental factor in autoimmune disorders. However, recent findings have challenged this common view, showing that PRL does not play a crucial role in the development of experimental autoimmune encephalomyelitis, animal model for multiple sclerosis (MS), and even protects against adjuvant-induced model of rheumatoid arthritis (RA). In this review we provide a critical overview of data supporting a role for PRL in the regulation of immune responses. In addition, we focus on studies exploring the involvement of PRL in autoimmune diseases, such as systemic lupus erythematosus, MS and RA, in light of the recently-outlined regenerative properties of this hormone., (Copyright © 2014 Elsevier B.V. All rights reserved.)

The immunomodulatory functions of prolactin (PRL) are well recognized. Augmented PRL plasma levels were observed in patients with advanced tuberculosis (TB). Recently, we have reported that LPS and Mycobacterium bovis (M. bovis) induced differential expression of PRL receptor (PRLR) isoforms in THP-1 cells and bovine macrophages, respectively. The aim of this work was to determine whether PRL should be considered as a potential modulator of the signaling pathways and cytokine synthesis, induced by culture filtrate protein (CFP) from M. bovis in THP-1 monocytes. The THP-1 cells were stimulated with PRL (20ng/mL), M. bovis CFP (50μg/mL). PRLR as well as phosphorylated STAT3, STAT5, Akt1/2/3, ERK1/2 and p38 expression were evaluated by Western blot. IL1-β, TNF-α, IL-6, IL-12, IL-8, and IL-10 concentrations were measured by ELISA. Our results demonstrated that the expression pattern of PRLR short isoforms is induced by M. bovis CFP. M bovis CFP induced phosphorylation of Akt2, ERK1/2, p38, STAT3, and STAT5 pathways. In turn, PRL only activated the JAK2/STAT3-5 signaling pathway. However, when combined both stimuli, PRL significantly increased STAT3-5 phosphorylation and downregulated Akt2, ERK1/2, and p38 phosphorylation. As expected, M. bovis CFP induced substantial amounts of IL1-β, IL-6, TNF-α, IL-8, IL-12, and IL-10. However, the PRL costimulation considerably decreased IL1-β, TNF-α, and IL-12 secretion, and increased IL-10 production. This results suggest that up-regulation of IL-10 by PRL might be modulating the pro-inflammatory response against mycobacterial antigens through the MAPK pathway., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

A strong gender bias is seen in many autoimmune diseases including systemic lupus erythematosus (SLE). To investigate the basis for the female preponderance in SLE, we have been studying BALB/c mice in which B cells express the R4A heavy chain of an anti-DNA antibody in association with an endogenous light chain repertoire (R4Atg mice). In unmanipulated mice, approximately 5% of B cells express the R4A transgene. R4Atg mice do not spontaneously develop elevated serum titers of anti-DNA antibodies. Administration of either estradiol (E2) or prolactin (Pr) results in escape from tolerance of autoreactive B cells, expressed as an increase in transgene-expressing B cells and elevated serum titers of anti-DNA antibodies. We previously demonstrated that autoreactive B cells maturing in an estrogenic milieu develop as marginal zone (MZ) B cells; when these same B cells mature in the presence of increased prolactin, they develop as follicular (Fo) B cells. To determine the long term consequence of this differential maturation of DNA-reactive B cells, we treated R4Atg BALB/c mice with E2 or Pr for 6 weeks until serum titers of anti-DNA antibody were high, at which time hormonal exposure was discontinued. In E2-treated mice, the anti-DNA titers remained high even 3 months after discontinuation of hormone exposure. Nascent B cells underwent normal tolerance induction, but existing autoreactive MZ B cells persisted and continued to secrete autoantibody. In contrast, Pr caused only a short-term increase in anti-DNA antibody titers. By 3 months after cessation of hormone treatment, serum anti-DNA antibody titers and B cell subsets were indistinguishable from those in placebo (P) treated mice. These findings suggest that autoantibody responses are sustained for variable lengths of time depending on the B cell subset producing the autoantibodies. This observation may be relevant to understanding the heterogeneous presentation of patients with SLE and to the design of therapies targeting specific B-cell populations in autoimmune disease., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Arthritic disorders are family of diseases that have existed since vertebrate life began. Their etiology is multifactorial with genetic, environmental, and gender factors driving chronic joint inflammation. Prolactin is a sexually dimorphic hormone in mammals that can act to both promote and ameliorate rheumatic diseases. It is found in all vertebrate groups where it exerts a wide diversity of actions. This review briefly addresses the presence and features of arthritic diseases in vertebrates, the effects of PRL on joint tissues and immune cells, and whether PRL actions could have contributed to the ubiquity of arthritis in nature. This comparative approach highlights the value of PRL as a biologically conserved factor influencing the development and progression of arthritis., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: We report a case of macroprolactin (macroPRL) in an 8-year-old girl complaining of an enlarged and painful breast who showed elevated PRL levels by enzyme immunoassay., Methods: Size-exclusion high-performance liquid chromatography (HPLC) was carried out on a Superose 12 column to estimate the PRL molecular profile. To identify the type of immunoglobulin bound to PRL, immunoprecipitation reactions were performed using three types of anti-heavy chain antibody and two types of anti-light chain., Results: PRL in the patient's serum was eluted at a size slightly larger than the IgG peak by size-exclusion HPLC on a Superose 12 column. In the immunoprecipitation reaction, the PRL concentration of the supernatant mixed with anti-gamma heavy chain and anti-κ light chain was dramatically decreased compared to other types of antiserum. These results indicated that macromolecular PRL was composed of PRL and IgG-κ., Conclusion: A rare case of PRL-IgG-κ-type complex was identified in the serum of the girl and the type of immunoglobulin light chain was determined for the first time. When encountering a child with hyperprolactinemia, pediatricians should take into account the possibility of macroPRL to avoid unnecessary investigation and/or treatment., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Prolactin (PRL) is a hormone synthesized and secreted by lactotroph cells in the anterior pituitary gland. There is also extrapituitary hormone secretion by many cells, including cells of the immune system. In physiological conditions PRL is responsible for lactogenesis and other processes associated with it. PRL plays a significant role during the immune response as a cytokine, affecting proliferation and differentiation of many immune system cells. The biological effect of the hormone depends on binding with the specific prolactin receptor PRL-R, and activation of the transcription factors of targeted genes. For T lymphocyte stimulated PRL, that factor is mainly the interferon regulatory factor (IRF-1), which gives the possibility of adjusting the prolactin immune response. Literature data indicate that hyperprolactinemia (HPRL) is one of the important factors in the pathogenesis and course of autoimmune diseases such as systemic lupus erythematosus, rheumatoid arthritis, systemic sclerosis and Sjogren's syndrome. HPRL is diagnosed in nearly one-third of these patients. However, only a few data indicate the role of prolactin in psoriatic arthritis (PsA), whose etiology and disease progression are not fully elucidated, and the diagnosis is very difficult. Currently there is indicated a pronounced connection between the course of HPRL and activity of PsA. It seems also to be interesting that, regardless of the PRL levels in serum of patients with PsA, administration of bromocriptine--drug-lowering hormone--improves joint and skin symptoms, which indicates a decrease in disease activity, and is a promising way of alternative therapy for psoriatic arthritis. However, the effect of PRL on the pathogenesis and the severity of psoriatic arthritis has not yet been fully understood and further research will provide a possibility to assess the prognostic and diagnostic significance of prolactin in patients with PsA.

The role played by prolactin (PRL) in fish immunity is scant. We report here that stimulation of the Atlantic salmon monocytic cell line SHK-1 with native salmon PRL resulted in activation of the respiratory burst and induction of the expression of the genes encoding the phagocyte NADPH oxidase components p47phox, p67phox and gp91phox, and the transcription factor IFN regulatory factor-1 (IRF-1). Interestingly, the pharmacologic inhibition of the Jak/Stat signaling pathway with AG490 blocked reactive oxygen species (ROS) production, and the induction of genes encoding the NADPH oxidase components and IRF-1 in PRL-activated SHK-1 cells. In addition, PRL promoted the phosphorylation of Stat and induced the DNA binding activity of IRF-1. These results, together with the presence of several consensus target motifs for Stat and IRF-1 in the promoter of the tilapia p47phox gene, suggest that PRL regulates p47phox gene expression in fish through the activation of these two key transcription factors. Taken together, our results demonstrate that PRL induces the expression of the genes encoding the major phagocyte NADPH oxidase components and ROS production in fish macrophages via the JAK2/Stat/IRF-1 signaling pathway.

The in vitro and in vivo effect of prolactin (PRL) on kidney macrophages from Atlantic salmon (Salmo salar) was investigated under the assumption that PRL stimulates immune innate response in mammals. Kidney macrophages were treated two ways: first, cultured in RPMI 1640 medium containing 10, 25, 50 and 100 ng/mL of PRL and second, isolated from a fish with a PRL-injected dose of 100 ng/Kg. Reduced nitro blue tetrazolium (formazan) was used to produce intracellular superoxide anion. Phagocytic activity of PRL was determined in treated cells by optical microscopy observation of phagocytized Congo red-stained yeast. Kidney lysozyme activity was measured in PRL-injected fish. In vitro and in vivo macrophages treated with PRL presented an enhanced superoxide anion production, elevated phagocytic index and increased phagocytic activity. Treated fish showed higher levels of lysozyme activity in the head kidney compared to the control. These results indicate that PRL-stimulated innate immune response in Atlantic salmon and future studies will allow us to assess the possibility of using PRL as an immunostimulant in the Chilean salmon industry.

Predominance of multiple sclerosis (MS) in women, reductions of disease flares during pregnancy, and their increase in the postpartum period have suggested a hormonal influence on MS activity. The hormone prolactin (PRL) has long been debated as a potential immune-stimulating factor in several autoimmune disorders, including MS and its animal model experimental autoimmune encephalomyelitis (EAE). However, to date, no data clearly ascribe a pathogenic role to PRL in these diseases. Using PRL receptor-deficient (Prlr(-/-)) and PRL-deficient (Prl(-/-)) mice, we show that PRL plays a redundant role in the development of chronic EAE. In Prlr(-/-) and Prl(-/-) mice, EAE developed with a delayed onset compared with littermate control mice, but with full clinical severity. In line with the clinical outcome, T cell proliferation and production of IFN-γ, IL-17A, and IL-6 induced by myelin Ag were delayed in Prlr(-/-) and Prl(-/-) mice. Ag-specific IgG Ab responses were not affected by PRLR or PRL deficiency. We also show that mouse lymph node cells and purified CD4(+) T cells express transcript for Prlr, but not for Prl. These results reveal that PRL does not play a central role in the development of chronic EAE and optimal Th1 and Th17 responses against myelin. Moreover, they also rule out a possible contribution of PRL secreted by immune cells to the modulation of autoreactive T cell response in this model.

Background: Pituitary and thyroid autoimmunity can be triggered by pregnancy. We report the first association of combined growth hormone (GH) and prolactin secretion deficiency due to autoimmune damage to GH- and prolactin-secreting cells in a patient with postdelivery lactation failure, presenting subsequently with primary autoimmune hypothyroidism., Patient Findings: A 34-year-old woman presented with lactation failure following the delivery of her first child. She had a family history of hypothyroidism without a history of pituitary dysfunction. Physical examination did not show any abnormal findings. Laboratory investigations showed normal gonadotropin levels after the restoration of normal menstrual cycles following pregnancy, normal basal and stimulated cortisol levels, but an impaired GH response to insulin-induced hypoglycemia, and low basal prolactin and insulin-like growth factor-1 concentrations. Thyroid function was normal when initially investigated three months after delivery, but five months later, marked primary hypothyroidism (thyrotropin levels >100 mIU/L) occurred. Immunological investigation revealed the presence of antipituitary antibodies, identified by double immunofluorescence and targeting GH- and prolactin-secreting cells. Antithyroid antibodies, in the normal range three months postpartum, became significantly elevated when the hypothyroidism appeared. Autoimmune hypophysitis is responsible for selective or multiple pituitary-hormone deficiencies, sometimes involving thyrotropin secretion and causing secondary hypothyroidism, but usually associated with hyperprolactinemia. To our knowledge, this is the first observation of autoimmune hypopituitarism involving deficient growth hormone and prolactin secretion in a patient with lactation failure after delivery, subsequently followed by severe primary autoimmune hypothyroidism, thus falling into an unusual constellation of autoimmune polyendocrine syndrome type 3., Conclusions: Considering the well-known relationship between pregnancy and autoimmunity, an early postdelivery immunological and functional investigation in women presenting with disorders of lactation may be useful to detect potential pituitary and thyroid dysfunction even at a subclinical stage.

Here, the effects of neurointermediate (NIL), anterior (AL), and total hypophysectomy (HYPOX) on ileal mucosa cells and gut-associated lymphoid tissue (GALT) are reported. Compared with the sham-operated (SHAM) rats, the villi height and goblet cells numbers were significantly decreased in all groups. Lamina propria area decreased in AL and HYPOX, but not in NIL animals. CD8(+) but not CD4(+) lymphocytes decreased in the HYPOX and NIL groups. Paneth cells did not change, while IgA cells, IgM cells, and secretory IgA were significantly decreased in all groups. NIL but not AL animals lost significant numbers of IgA cells and secretory IgA. In summary, pituitary hormones exert lobe-specific regulatory effects on the gut and on GALT., (© 2012 New York Academy of Sciences.)

Disorders in the hypothalamic-pituitary-adrenal axis are associated with the pathogenesis of Trypanosoma cruzi infection. During the acute phase of this disease, increased levels of circulating glucocorticoids (GCs) correlate with thymic atrophy. Recently, we demonstrated that this phenomenon is paralleled by a decrease of prolactin (PRL) secretion, another stress hormone that seems to counteract many immunosuppressive effects of GCs. Both GCs and PRL are intrathymically produced and exhibit mutual antagonism through the activation of their respective receptors, GR, and PRLR. Considering that GCs induce apoptosis and inhibit double-positive (DP) thymocyte proliferation and that PRL administration prevents these effects, it seems plausible that a local imbalance of GR-PRLR crosstalk underlies the thymic involution occurring in acute T. cruzi infection. In this respect, preserving PRLR signaling seems to be crucial for protecting DP from GC-induced apoptosis., (© 2012 New York Academy of Sciences.)

A novel class of redox-active molecular tags, poly(o-phenylenediamine)-carried nanogold particles (GPPDs), was first synthesized and functionalized with horseradish peroxidase-anti-prolactin conjugates (HRP-anti-PRL). Thereafter, a specific sandwich-type electrochemical immunoassay was designed for determination of prolactin (PRL) by using GPPD-labeled HRP-anti-PRL conjugates as molecular tags on anti-PRL antibody-modified glassy carbon electrode. Compared with pure gold nanoparticles and poly(o-phenylenediamine) microspheres, the as-prepared GPPDs increased the surface coverage of the nanostructures, and enhanced the immobilization amount of biomolecules. Several labeling protocols compromising GPPD-labeled HRP-anti-PRL, nanogold particles-labeled HRP-anti-PRL and poly(o-phenylenediamine) microspheres-labeled HRP-anti-PRL, were investigated for detection of PRL, and improved analytical features were obtained with the GPPD-based strategy. With the GPPD labeling method, dependence of the electrochemical signals on the incubation time and pH of the assay solution were also studied. The strong attachment of HRP-anti-PRL to the GPPDs resulted in a good repeatability and intermediate reproducibility down to 9.8%. The dynamic concentration range spanned from 0.5 to 180 ng mL(-1) PRL with a detection limit of 0.1 ng mL(-1) at the 3S(blank) level. No significant differences at the 95% confidence level were encountered in the analysis of 10 spiked blank cattle serum samples between the developed immunoassay and enzyme-linked immunosorbent assay method for determination of PRL., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Sex hormones, especially estrogen and prolactin (PRL), have an important role in modulating the immune response. PRL is secreted from the pituitary gland as well as other organs and cells particularly lymphocytes. PRL has an immune stimulatory effect and promotes autoimmunity. PRL interferes specifically with B cell tolerance induction, enhances proliferative response to antigens and mitogens and increases the production of immune globulins, cytokines and autoantibodies. Hyperprolactinemia (HPRL) in women present with clinical manifestations of galactorrhea, primary or secondary amenorrhea, delayed menarche or a change in the menses either in the amount or in the regularity. Furthermore in the last 2 decades multi-organ and organ specific autoimmune diseases like systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), Sjogren's syndrome (SS), Hashimoto's thyroiditis (HT), multiple sclerosis (MS), psoriasis, hepatitis C patients, Behçet's disease, peripartum cardiomyopathy (PPCM) and active celiac disease were discussed to be associated with HPRL. There is data showing correlation between PRL level and diseases activity in few diseases. Genetic factors may have a role in humans as in animal models. The PRL isoforms based on the differences in the amino acid sequence and size of the cytoplasmic domain have an important effect on the bioactivity on prolactin receptors (PRL-Rs)., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Evidence points to an association of prolactin to autoimmune diseases. We examined the correlation between hyperprolactinemia and disease manifestations and activity in a large patient cohort. Age- and sex-adjusted prolactin concentration was assessed in 256 serum samples from lupus patients utilizing the LIASON prolactin automated immunoassay method (DiaSorin S.p.A, Saluggia, Italy). Disease activity was defined as present if European Consensus Lupus Activity Measurement (ECLAM) > 2 or Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) > 4. Lupus manifestations were grouped by organ involvement, laboratory data, and prescribed medications. Hyperprolactinemia was presented in 46/256 (18%) of the cohort. Hyperprolactinemic patients had significantly more serositis (40% vs. 32.4%, p = 0.03) specifically, pleuritis (33% vs. 17%, p = 0.02), pericarditis (30% vs. 12%, p = 0.002), and peritonitis (15% vs. 0.8%, p = 0.003). Hyperprolactinemic subjects exhibited significantly more anemia (42% vs. 26%, p = 0.02) and marginally more proteinuria (65.5% vs. 46%, p = 0.06). Elevated levels of prolactin were not significantly associated with other clinical manifestations, serology, or therapy. Disease activity scores were not associated with hyperprolactinemia. Hyperprolactinemia in lupus patients is associated with all types of serositis and anemia but not with other clinical, serological therapeutic measures or with disease activity. These results suggest that dopamine agonists may be an optional therapy for lupus patients with hyperprolactinemia.

Objective: Macroprolactinaemia is a condition in which serum prolactin (PRL) consists mainly of large molecular weight PRL (macroPRL). The aim of this study was to examine the natural history of macroprolactinaemia., Design and Participants: Six hundred and fifty-four hospital workers participated in this study, including 27 subjects with macroprolactinaemia and 627 controls. MacroPRL and serum PRL concentrations were evaluated over a 4-year period. The ratio of macroPRL was examined by the polyethylene glycol (PEG) method and gel filtration chromatography. IgG-bound PRL and anti-PRL autoantibodies were examined by protein G and (125)I-PRL binding studies respectively., Results: Over the 4 years of the study, all 27 macroprolactinaemic subjects had persistent macroprolactinaemia without the development of raised free PRL, while none of the 627 controls developed macroprolactinaemia. The ratios of PEG-precipitable PRL and IgG-bound PRL did not significantly change, but (125)I-PRL binding ratios significantly increased. As a whole, total and free serum PRL concentrations did not significantly change in subjects with macroprolactinaemia over the 4-year period. However, hyperprolactinaemia developed in five of the 18 macroprolactinaemic subjects who were initially normoprolactinaemic along with an increase in anti-PRL autoantibody titres. One of the remaining nine macroprolactinaemic subjects who were initially hyperprolactinaemic showed a decrease in serum PRL concentrations, which occurred concomitantly with a decrease in the anti-PRL autoantibody titre., Conclusions: Macroprolactinaemia may develop before middle age and is likely a chronic condition leading to hyperprolactinaemia.

Fasting serum prolactin (PRL) levels in response to metoclopramide (MCP) and lymphocyte cytokine profiles was studied in patients given allografts and their donors. Thirty normoprolactinemic volunteers (12-59 years) were studied: group 1, 10 healthy men; group 2, 8 males and 2 females with various hematologic diseases; and group 3, 3 males and 7 females HLA-identical sibling donors: PRL and cytokines were measured. Four surviving recipients developed acute graft-versus-host disease (GVHD) (+), and six did not. Before transplant Fasting PRL concentrations were higher in 'future' GVHD(+) recipients than in their donors (P < 0.001). The opposite was seen in response to MCP (P = 0.01). Donors had a predominant T-helper type 1 (Th1) cytokine profile compared with recipients (P ≤ 0.02), and GVHD(+) recipients had a greater tumor necrosis factor (TNF) value than GVHD(-) (P = 0.05). After transplant On days +30 and +100, a mild sustained rise in fasting PRL levels occurred only in GVHD(+) recipients (P ≤ 0.05) simultaneously with a transient rise in Th1 cytokines. GVHD(-) recipients had no changes. Donors with a Th1 cytokine profile might be more prone to induce GVHD in their recipients, and a mild sustained rise in PRL concentrations after transplantation in recipients GVHD(+) might participate in the amelioration of the severity of GVHD.

Prolactin is a hormone with a multidirectional proinflammatory action. It has an anti-apoptotic effect, enhances proliferative response to antigens and mitogens, as well as enhances the production of immunoglobulins and autoantibodies. Increased prolactin levels are commonly observed in various organ and multi-organ specific autoimmune diseases. In our article, we report a case of a woman who developed progression of autoimmune thyroid disorder and developed insufficiency of the zona glomerulosa when her prolactin levels were increased. A normalization of plasma prolactin levels by quinagolide and replacement of risperidone with aripiprazole improved her clinical condition. Our study suggests that, in some patients, hyperprolactinemia may predispose to the development and progression of autoimmune disorders of endocrine glands.

Background: Prolactin in schizophrenia is considered in the context of antipsychotic drug-induced hyperprolactinemia. However, the European First Episode Schizophrenia Trial showed that hyperprolacti nemia occurred in a significant proportion of drug-naïve first-episode schizophrenia patients, which shows that it may also be caused by other factors, including genetic predisposition. Therefore, we investigated the functional polymorphism of the prolactin gene in schizophrenic patients compared with control subjects., Method: The experimental group consisted of 403 patients with schizophrenia: 202 females and 201 males. The control group consisted of 653 subjects: 377 females and 276 males. The functional polymorphism -1149 G/T (rs1341239) of the prolactin gene was genotyped using the TaqMan single-nucleotide polymorphism allelic discrimination method., Results: The distribution of genotypes in schizophrenic patients was significantly different from those of the control subjects (p=0.031). After breaking down by gender, for male patients, the difference versus control males was significant for both genotypes and alleles (p=0.031 and p=0.002, respectively), with allele G being observed more frequently in schizophrenic patients., Conclusion: The results may suggest a possible abnormality of the functional -1149 G/T polymorphism of the prolactin gene in schizophrenia, especially in male patients, similar to that found in autoimmune diseases such as systemic lupus erythematosus and rheumatoid arthritis. This could also correspond with an autoimmune pathogenesis of schizophrenia., (Copyright © 2011 S. Karger AG, Basel.)

The pituitary hormone prolactin (PRL) is a multifunctional polypeptide which act as a key component of the neuroendocrine-immune loop and as a local regulator of the macrophage response. The involvement of PRL in regulating monocyte/macrophage functions is suggested by the presence of PRL receptors in these cells. Recently, we reported that physiological concentrations of native PRL were able to induce the expression of the pro-inflammatory cytokines IL-1β and TNFα, and the production of reactive oxygen species (ROS) in head kidney leukocytes and macrophages from the teleost fish gilthead seabream (Sparus aurata L.). In this study, we show that the NADPH oxidase subunit p47phox becomes phosphorylated in leukocytes stimulated with PRL, an effect that is blocked when neutralizing polyclonal antibodies to PRL are added. Additionally, the pharmacological inhibition of either protein kinase C (PKC) with calphostin C or the Jak/Stat signaling pathway with AG490 impaired PKC activation, p47phox phosphorylation and ROS production in seabream leukocytes activated with PRL. Taken together, our results demonstrate for the first time the need for PKC in regulating the PRL-mediated phosphorylation of p47phox, the activation of NADPH oxidase and the production of ROS by macrophages in vertebrates., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Objectives: To determine if elephant placenta secretes a lactogenic hormone which may function as the principal luteotrophin to maintain ovarian luteal function throughout gestation., Study Design and Main Outcome Measures: To label biopsies of endometrium and placenta recovered from African elephant culled professionally throughout gestation with an anti-human prolactin polyclonal antibody in a conventional immunocytochemical staining technique., Results: All trophoblast cells covering the placental villi and forming 'plugs' in the apical endometrial glands stained strongly and precisely with the anti-human prolactin antiserum throughout gestation., Conclusions: Elephant trophoblast secretes a placental lactogen (elPL) which may stimulate both the development and secretory function of the large accessory corpora lutea of elephant pregnancy and provide the mitogenic stimulus for placental differentiation and development., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

A novel electrochemical immunosensor was developed for the determination of the hormone prolactin. The design involved the use of screen-printed carbon electrodes and streptavidin-functionalized magnetic particles. Biotinylated anti-prolactin antibodies were immobilized onto the functionalized magnetic particles and a sandwich-type immunoassay involving prolactin and anti-prolactin antibody labelled with alkaline phosphatase was employed. The resulting bio-conjugate was trapped on the surface of the screen-printed electrode with a small magnet and prolactin quantification was accomplished by differential pulse voltammetry of 1-naphtol formed in the enzyme reaction using 1-naphtyl phosphate as alkaline phosphatase substrate. All variables involved in the preparation of the immunosensor and in the electrochemical detection step were optimized. The calibration plot for prolactin exhibited a linear range between 10 and 2000 ng mL(-1) with a slope value of 7.0 nA mL ng(-1). The limit of detection was 3.74 ng mL(-1). Furthermore, the modified magnetic beads-antiprolactin conjugates showed an excellent stability. The immunosensor exhibited also a high selectivity with respect to other hormones. The analytical usefulness of the immnunosensor was demonstrated by analyzing human sera spiked with prolactin at three different concentration levels., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Background: Ferritin and prolactin have been associated with active autoimmune diseases as systemic lupus erythematosus and autoantibody production, but have been little studied in viral infections that present autoimmunity., Objective: To investigate the association of these two autoimmune mediators with the presence of cryoglobulinaemia and non-organ-specific autoantibodies (RF, SMA, β2GPI IgA antibody and ANA) in Brazilian individuals chronically infected with hepatitis C virus (HCV)., Methods: Ninety-nine patients were evaluated. Ferritin and prolactin levels were determined by chemiluminescent immunoassays., Results: Hyperprolactinemia was found in 10 (six men and four women) out of 99 (10.1%) hepatitis C patients. Thirty-eight out of 99 (38.4%) HCV carriers had hyperferritinemia (median level 385ng/mL). Neither hyperprolactinemia nor hyperferritinemia was associated with cryoglobulinaemia or non-organ-specific autoantibodies (p>.05). There was an association between hyperprolactinemia and the infection with HCV genotype 3 (p<.01). Ferritin and ALT levels were correlated (p<.05)., Conclusion: Our results suggest that neither prolactin nor ferritin is involved with the extra-hepatic manifestation of autoimmunity observed in HCV carriers., (Copyright © 2010 Elsevier B.V. All rights reserved.)

The predominant prevalence of autoimmune diseases in women of reproductive age has led to the investigation of the effects of sex hormones on immune regulation and in autoimmune diseases, in particular the prototypic systemic autoimmune disease lupus. The female hormone prolactin has receptors beyond the reproductive axis including immune cells, and it is thought to promote autoimmunity in human and murine lupus. Induced hyperprolactinemia in experimental lupus models, regardless of gender, exacerbates disease activity and leads to premature death. Prolactin treatment in mice that are not prone to develop lupus leads to the development of a lupus-like phenotype. Persistent mild-moderate hyperprolactinemia alters the selection of the naïve B cell repertoire. Recent studies demonstrate that prolactin impairs all three mechanisms of B cell tolerance induction (negative selection, receptor editing, and anergy) and thereby contributes to the pathogenesis of autoimmunity. The effects of prolactin are genetically determined as shown by the differential response to the hormone in the different mice strains. Bromocriptine, a drug that inhibits prolactin secretion, abrogates some of the immune effects of this hormone. Further research is required to elucidate molecular mechanisms involved in immune effects of prolactin and to develop novel targeted treatments for SLE patients with prolactin-responsive disease.

The relationship between prolactin and the immune system has been demonstrated in the last two decades, opening new windows in the field of the immunoendocrinology. Prolactin has an important role in the innate and adaptive immune response. Increased prolactin levels have been described in autoimmune diseases such as systemic lupus erythematosus, rheumatoid arthritis, Sjögren syndrome, and systemic sclerosis among others. Hyperprolactinemia is associated with active disease and organ involvement in systemic lupus erythematosus. Therefore, prolactin is an integral member of the immunoneuroendocrinology network and seems to have a role in pathogenesis of autoimmune diseases. Few controlled studies of dopamine agonist treatment in humans with autoimmune disease have been conducted only in systemic lupus erythematosus patients, which support the potential efficacy of such agents even during pregnancy and postpartum. Further studies are necessary to elucidate the mechanisms by which prolactin affects autoimmune disease activity, increase the inflammatory mechanism, and determine the role of anti-prolactinemic drugs to regulate the immune/inflammatory process.

The relationship between prolactin (PRL) and the immune system has been demonstrated in the last two decades and has opened new windows in the field of immunoendocrinology. However, there are scarce reports about PRL in primary antiphospholipid syndrome (pAPS). The objective of this study was to evaluate PRL levels in patients with pAPS compared to healthy controls and to investigate their possible clinical associations. Fifty-five pAPS patients according to Sapporo criteria were age- and sex-matched with 41 healthy subjects. Individuals with secondary causes of hyperprolactinemia (HPRL) were excluded; demographic, biometric, and clinical data, PRL levels, antiphospholipid antibodies, inflammatory markers, and other routine laboratory findings were analyzed. PRL levels were similar between pAPS and healthy controls (8.94 ± 7.02 versus 8.71 ± 6.73 ng/mL, P = .876). Nine percent of the pAPS patients and 12.1% of the control subjects presented HPRL (P = .740). Comparison between the pAPS patients with hyper- and normoprolactinemia revealed no significant differences related to anthropometrics, clinical manifestations, medications, smoking, and antiphospholipid antibodies (P > .05). This study showed that HPRL does not seem to play a role in clinical manifestations of the pAPS, differently from other autoimmune rheumatic diseases.