Abstract
Objectives
Patients with type 1 diabetes mellitus have been reported to have elevated prolactin levels and a possible relationship between prolactin levels and the development of the disease has been proposed. However, some studies show that prolactin mediates beneficial functions in beta cells. Therefore, we review information on the roles of prolactin in type 1 diabetes mellitus.
Content
Here we summarize the functions of prolactin in the immune system and in pancreatic beta cells, in addition, we describe studies related to PRL levels, its regulation and alterations of secretion in patients with type 1 diabetes mellitus.
Summary
Studies in murine models have shown that prolactin protects beta cells from apoptosis, stimulates their proliferation and promotes pancreatic islet revascularization. In addition, some studies in patients with type 1 diabetes mellitus have shown that elevated prolactin levels correlate with better disease control.
Outlook
Prolactin treatment appears to be a promising strategy to improve beta-cell vascularization and proliferation in transplantation and immunotherapies.
Highlights
Prolactin is involved in several processes related to the etiology of type 1 diabetes mellitus, such as activation of the immune system, angiogenesis, and beta-cell survival and proliferation.
Observational studies evaluating prolactin levels in patients with type 1 diabetes mellitus are not consistent.
Studies in murine models have shown that prolactin enhances vascularization and proliferation in pancreatic islets.
Further studies are required to assess the positive and negative aspects of prolactin-based therapies.
Introduction
Prolactin (PRL) is a hormone that at high concentrations stimulates proinflammatory immune responses [1]. Since increased PRL has been reported in several autoimmune diseases, this hormone has been proposed to be involved in the development of autoimmune diseases, such as systemic lupus erythematosus and rheumatoid arthritis among others [2, 3]. However, the relationship of PRL levels with other autoimmune diseases such as type 1 diabetes mellitus (T1DM) is unclear.
Several reviews on the role of prolactin and autoimmune diseases have repeatedly cited that patients with T1DM have hyperprolactinemia [4], [5], [6], [7], [8], [9], which coupled with the functions of prolactin in the immune system, has led to posit a possible relationship between prolactin levels and T1DM [1]. However, reports evaluating prolactin levels in patients with T1DM are heterogeneous and the results are not consistent [10], [11], [12].
Prolactin has also shown beneficial effects on pancreatic cells, such as stimulating their proliferation, protecting against apoptosis, favoring angiogenesis in pancreatic islet transplants and increasing insulin production [13], [14], [15]. Conversely, the detrimental role that had been associated with PRL in T1DM could be misunderstood. Therefore, in this review the PRL functions on the immune system and pancreatic beta cells, besides, the evidence showing the role of prolactin in murine models and patients with T1DM are summarized, in order to contribute to clarified PRL dual effects.
Biology of prolactin and its receptor
PRL is a lactogenic hormone produced mainly by the lactotrophs cells of the anterior pituitary gland [16]. Its release is stimulated by serotonin, thyrotropin-releasing hormone and vasoactive intestinal peptide, and it is inhibited by dopamine and opioids [16, 17]. More than 300 functions have been described for PRL hormone, which fall into six main categories 1) water and electrolyte balance, 2) growth and development, 3) endocrinology and metabolism, 4) brain and behavior, 5) reproduction, and 6) immunoregulation and protection [18]. In humans, it has been shown that the synthesis and secretion of this hormone is not restricted to the pituitary gland, but is synthesized extrapituitarily by other body tissues such as the decidua, brain, adipose tissue, skin follicles, endothelial cells, and immune cells [19].
Both pituitary and extrapituitary PRL are single-chain globular proteins with 199 amino acids and have a molecular mass of 23 kDa [16]. However, several isoforms resulting from posttranslational modifications have been described that have different molecular weights. These modifications can be phosphorylation, glycosylation and proteolytic cleavage, in addition, PRL can polymerize (macroprolactin) or interact with antibodies (bigbig PRL) [17, 20].
The PRL receptor (PRL-R) is a transmembrane protein belonging to the class-1 cytokine receptor superfamily [18]. Its gene is located on chromosome five in humans and on chromosome 15 in murine, this gene encodes different isoforms by the process of alternative splicing [21]. The different isoforms exhibit an identical extracellular domain, but differ in length and composition of the intracellular portion. Depending on the size of the intracellular region, the three main receptors are the long (PRLR-L, 85–90 kDa), intermediate (PRLR-I, 65 kDa) and short (PRLR-S, 42 kDa) isoforms. A soluble receptor for PRL has also been described in humans [21, 22]. Expression of PRL-R has been demonstrated in cells of the brain, retina, cartilage, skin, lung, heart, pancreas, liver, spleen, thymus, intestinal tract, kidney, reproductive system, and cells of the immune system such as B cells, T cells and macrophages [18, 21].
Prolactin and its effect on the immune system
In 1930, the first evidence suggesting the involvement of PRL in the immune system was reported by Smith and cols. They observed that hypophysectomy in rats caused atrophy of the thymus [23]. In 1978, Nagy and Berci reported that hypophysectomized rats developed immunodeficiencies and these were restored by administration of PRL, growth hormone and placental lactogen [24]. In later studies, treatment of rats with the dopaminergic agonist bromocriptine, which inhibits pituitary PRL secretion, was observed to decrease the cellular and humoral immune response; the immune response was restored upon discontinuation of bromocriptine treatment [25]. Thereafter, multiple roles of PRL in the immune system have been reported. Early studies suggested a proinflammatory role of PRL, but subsequent work has shown that PRL also has anti-inflammatory and repair functions [18, 26]. In the following, we will describe the main functions of this hormone in the immune system.
Apart from the dopaminergic and hormonal control of PRL, cytokines are able to regulate PRL secretion [27]. Interleukin (IL)-1, IL-2, IL-6 and tumor necrosis factor-alpha (TNF-α) can act as paracrine or endocrine regulators in PRL release, whereas endothelin 3, transforming growth factor-beta (TGF-β) and interferon gamma (IFN-γ) inhibit its secretion [1, 28, 29]. In addition, several cells of the immune system such as thymocytes and mononuclear cells are able to synthesize PRL, and its synthesis in these cells can be regulated by cytokines and hormones [30], [31], [32].
Immune system cells such as T cells, B cells and Natural Killer (NK) cells express PRL receptor [21, 33], through which this hormone is able to mediate many functions in the immune system, such as inducing proliferation and differentiation of T cell precursors [34], increase the adhesion of mononuclear cells with epithelial cells, participate in the expression of the chemokine receptor CXCR3 and inhibit the suppressive capacity of regulatory T cells [35, 36]. In addition, PRL is involved in the expression of activation-related molecules CD69 and CD154 on CD4+ T cells [37] and of CD69 and CD25 on CD8+ T cells [38]. Thus, PRL acts as a co-mitogen and coactivator in T cells. In the case of B cells, prolactin increases the maturation of these cells and the production of autoantibodies [39].
PRL also regulates cytokine secretion. For example, in whole blood cells PRL is able to stimulate the secretion of IFN-γ, IL-12 and IL-10 [40], in dendritic cells PRL increases IL-12, TNF-α and IL1-β secretion [41], in mononuclear cells it increases the secretion of IL-12 and TNF-α [42] and in activated T cells it favors the expression of IL-2 and IFN-γ [37]. In these cases, PRL alone does not stimulate the secretion of inflammatory cytokines; the effect is only observed when the cells are stimulated with another molecule such as lipopolysaccharide, phytohemagglutinin or Phorbol 12-myristate 13-acetate (PMA). For a broader review of the functions of prolactin on the immune system we recommend the following articles [1, 26, 33].
PRL also has anti-inflammatory functions. For example, PRL reduces TNF-α and IL-1β expression in chorioamniotic membrane explants in human term gestation [43] and decreases TNF-α, IL-1β and IL-6 secretion in lipopolysaccharide (LPS)-stimulated human placentas [44]. In the nervous system, PRL decreases glia activation [45, 46] and in lung fibroblasts, PRL inhibits the expression of the enzyme inducible nitric oxide synthase thereby blocking the production of oxygen free radicals [47].
The dual function of PRL in the immune system has been related to several factors such as: 1) the concentration of PRL, 2) the time of stimulation, 3) the isoform of PRL, 4) the isoform of its receptor and 5) the presence of cytokines and pathogen-associated molecular patterns (PAMPs) in the medium [26]. For example, PRL induces the production of TNF-α, IL-1β and nitric oxide (NO) in bovine mammary gland epithelial cells, but when these cells are stimulated with PRL in the presence of Staphylococcus aureus the production of IL-1β, nitric oxide and β-defensin decreases [48], furthermore, in the monocyte cell line (THP1), PRL decreases IL1-β, TNF-α and IL-12 secretion, and increases IL-10 secretion when co-administered with PAMPs from Micobaterium bovis, in contrast when PRL acts alone in THP1 cells it has no effect on cytokine secretion [49].
Prolactin effects in beta cells
PRL has functions related to glycemic control and homeostasis in pancreatic beta cells. For example, PRL stimulates beta cell proliferation, increases insulin synthesis, islet vascularization and has anti-apoptotic effects (Figure 1) [13], [14], [15]. Mice with reduced PRL receptor expression (Prlr ±) have elevated blood glucose levels, decreased β-cell mass and decreased glucose-stimulated insulin secretion compared to mice expressing normal levels of PRL receptor (Prlr +/+) [50].
Modular effect of prolactin in type 1 diabetes mellitus. Prolactin participates in the control of inflammation by stimulating immune system cells such as T cells and B cells, in addition, it reduces the suppressive capacity of regulatory T cells (T reg). Mediators released by immune system cells induce apoptosis in pancreatic beta cells. In turn, prolactin is converted to vasoinhibins by the action of proteases; these vasoinhibins have apoptotic, anti-angiogenic and vasoconstrictive effects. On the other hand, prolactin has positive effects on beta cells such as reducing apoptosis by regulating the expression of apoptotic and anti-apoptotic genes (see text) and inducing the expression of heat shock protein B1 (HSPB1). In addition, prolactin stimulates beta-cell proliferation by inducing survivin and serotonin expression, inducing angiogenesis.
In the streptozotocin-treated mouse model, it has been reported that mice lacking the PRL receptor show higher glucose levels and a higher rate of cases compared to mice that do express the PRL receptor, in addition, mice lacking the PRL receptor have a lower number of beta cells, lower levels of surrounding insulin and increased pancreatic inflammation [51]. Thus, PRL is a hormone involved in pancreatic beta-cell homeostasis and ample evidence supports its protective role in diabetes. Below, we describe some of the functions mediated by PRL on beta cells.
Anti-apoptotic effect
In rat pancreatic islet cultures, PRL prevents beta cell death induced by inflammatory cytokines such as IFNγ, TNFα and IL-1β. This antiapoptotic effect was mediated through the activation of signal transducer and activator of transcription 3 (STAT3) and inhibition of the expression of proapoptotic genes such as Bim small (BimS) and p53 upregulated modulator of apoptosis (PUMA) [15]. Other studies in both rat and human pancreatic islets reported that PRL also increases the expression of the anti-apoptotic genes BCLxl (B-cell lymphoma-extra large) [15] and BCL2/BAX (B-cell lymphoma two/BCL2 Associated X) [52], in addition to inhibiting caspases −3, −8 and −9 [53].
Another mechanism by which PRL indirectly protects against apoptosis is by increasing the expression of HSPB1 (heat shock protein B1), which is involved in the protection against endoplasmic reticulum stress and apoptosis in mouse beta-cell cultures. HSPB1 participates in the augmented degradation of proapoptotic proteins [54, 55]. In addition, HSPB1 also restores mitochondrial dysfunction in mouse insulinoma-derived MIN6 cells exposed to inflammatory cytokines [56].
Proliferative effect
PRL has been shown to promote proliferation, growth and insulin production in pancreatic beta cells by activating the transcriptional factor signal transducer and activator of transcription 5 (STAT5). Mice deficient in functional STAT5 show reduced beta-cell proliferation and are more susceptible to develop diabetes upon treatment with low-dose streptozotocin [57]. In mouse islets during pregnancy, signaling through the STAT5, Akt and ERK(Extracellular signal-regulated kinase) pathway induces expression of survivin; a protein involved in apoptosis inhibition and cell cycle regulation, and which is required to mediate the proliferative effect of PRL [58].
In the INS-1 beta cell line it was observed that PRL stimulates proliferation in a glucose concentration-dependent manner, at low glucose concentrations phosphorylation of phosphatidylinositol-3′-kinase (PIK-3) occurs through Insulin Receptor Substrate (IRS)-2, at physiological concentrations through IRS-4 and at high concentrations through IRS-1 [59]. This dependence on glucose concentration to induce proliferation has also been reported for growth hormone and hepatocyte growth factor in the INS-1 beta cell line [60, 61].
Some indirect mechanisms through which PRL induces beta-cell proliferation is by inducing serotonin expression through STAT5 activation [62]. In C57BL/6J mice, serotonin induces beta-cell proliferation in an autocrine and paracrine manner through interaction with serotonin receptor 2B (HTR2B), in addition, intracellular serotonin has antioxidant functions that mitigate oxidative stress and increase survival in mice treated with alloxan, a diabetogenic toxin [63, 64].
During pregnancy, beta-cell proliferation increases as a mechanism of adaptation to new physiological demands [65, 66], and since PRL secretion is increased during pregnancy, it has been proposed that this hormone has a fundamental role in homeostatic control in this period [67].
Angiogenic effect
PRL stimulates angiogenesis in pancreatic islets and has been shown to be effective in promoting transplantation vascularization in murine models [68]. In C57BL/6 mice, it was observed that if pancreatic islets were treated with PRL before transplantation, there was a 50% increase in vascular density compared to mice that received pancreatic islet transplants not treated with PRL [68]. In this study, an increase in blood perfusion, oxygen tension and graft volume was also observed in PRL-treated transplants [68].
This angiogenic effect of PRL is mediated by activation of STAT5, whose activation is required to induce migration, invasion and formation of tubular structures by endothelial cell lines [69, 70]. The angiogenic functions of PRL have been extensively reviewed by Clapp et al. (2008 and 2009), and Yang and Friedl (2015) [69, 71, 72].
The angiogenic effect of PRL dependent on its conversion to vasoinhibins, which are fragments of PRL with antiangiogenic, proapoptotic and vasoconstrictive properties [73]. This conversion is performed by proteases such as cathepsin D and matrix metalloproteases [73]. The conversion of PRL to vasoinhibins takes place in the anterior pituitary gland, but they can also be generated in target tissues [74]. In streptozotocin-treated rats, hyperprolactinemia has been proposed to protect against diabetic retinopathy -despite the fact that PRL has an angiogenic function-due to the conversion of PRL to vasoinhibins in the eye [75].
Type 1 diabetes
T1DM is a chronic autoimmune disease in which there is selective destruction of the β-cells of the pancreas. It can occur at any age, but its highest incidence is seen in children under 15 years of age, most often in preschool and especially prepubertal age (DiMeglio et al., 2018). It is not known what triggers the immune response against β-cells or whether it is a stochastic event. Several factors have been linked to the development of T1DM such as diet, vitamin D insufficiency, decreased gut-microbial diversity, obesity, genetic load and infections [76, 77].
T1DM has long been associated with a T cell-mediated immune response [78], this is due to the association of T1DM with human leukocyte antigens (HLA) genes [79, 80], the presence of autoreactive CD4+ and CD8+ T cells against pancreatic islet antigens [81], and decreased suppressive capacity of regulatory T cells [82], in addition, B cells are involved in antigen presentation to T cells and autoantibody production, and B cell depletion delays disease progression [83], [84], [85].
Prolactin and its relationship to type 1 diabetes
High levels of PRL have been associated with various autoimmune diseases, probably due to increased bidirectional communication between the immune and endocrine systems and the inflammatory functions of PRL. Hyperprolactinemia has been described in some autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus, and T1DM [1, 8]. In the following sections we discuss the evidence supporting the involvement of PRL in the etiopathogenesis of T1DM in both murine models and humans.
Studies in murine models
Early approaches to the effect of PRL on glycemia in diabetes were addressed with the use of D2-dopaminergic agonists such as bromocriptine. These agonists inhibit the pituitary release of PRL and treatment with them has shown a beneficial effect in autoimmune diseases such as arthritis, uveitis and systemic lupus erythematosus [86, 87]. However, in the case of T1DM, the results of bromocriptine treatment have not been consistent.
A study in NOD mice, a murine model of T1DM, showed that when hypoprolactinemia was caused by subcutaneous injection of CB-154 (2-bromo-alpha-ergocryptine) there was a decrease in the incidence of diabetes in female mice [88]. However, another study in NOD mice, a spontaneous model of autoimmune type 1 diabetes, reported that intraperitoneal bromocriptine treatment accelerated the development of diabetes in male mice and increased the number of islets with perinsulitis [89]. Subsequently, it was determined that the difference in these results is related to the route of administration of bromocriptine, since intraperitoneal administration favors hyperglycemia [90].
The difficulty in analyzing the results obtained with bromocriptine is due to the fact that it does not inhibit extrapituitary PRL synthesis [91, 92], furthermore, it has been described that bromocriptine induces hyperglycemia through D2-dopaminergic receptor-dependent signals in NOD mice [90] and this hyperglycemic effect may mask the immunomodulatory effect of PRL.
Another method of addressing the question was the administration of PRL in several murine models of diabetes, where a beneficial effect of PRL has been shown. For example, mice treated with streptozotocin plus PRL had less insulitis and lower elevation of glucose levels than mice treated with streptozotocin alone [93]. This protective effect was related to a shift of the inflammatory response profile towards a Th2 type by PRL, as it induced an increase in the percentage of IL-10 positive spleen cells and reduced the expression of IL-1β and TNFα mRNA [94].
The beneficial effect of PRL administration has not only been related to its immunomodulatory capacity, but also to its ability to protect from apoptosis and induce beta-cell proliferation. Therefore, PRL has been applied as a complementary treatment in transplantation and immunotherapies. For example, PRL treatment improves beta cell function in mice that have received fetal pancreas transplantation, in which an improvement in revascularization, blood perfusion and oxygen tension is observed [95], this improvement in transplantation was also observed when human islets were transplanted in syngeneic mice [68].
As for T-cell depletion therapy with anti-CD3, co-treatment with PRL has shown extra benefits. For example, in a study in NOD mice, co-treatment with anti-CD3 plus PRL was observed to normalize glycemia levels and improve the remission rate compared to treatment with anti-CD3 alone, furthermore, co-treatment increased the rate of beta-cell proliferation, pancreatic insulin content and glucose-stimulated insulin release [96].
Studies in animal models seem to support a beneficial effect of PRL in T1DM, and not something detrimental as expected due to its proinflammatory effects. However, PRL can mediate different functions depending on its concentration and the inflammatory mediators present in the medium as discussed above [26]. This concentration-dependent effect of PRL has also been observed in glycemic control. Treatment of rats with high doses of PRL (250 μg/kg bw/12 h) has been reported to cause glucose intolerance, hyperinsulinemia and insulin resistance, but lower PRL concentrations (25 μg/kg bw/12 h) improvement of insulin secretion and sensitivity [97]. Therefore, the concentration and route of admiration should be considered in future studies.
Clinical studies
Hyperprolactinemia has been reported in patients with T1DM. For example, in a study of 58 male patients with T1DM, it has been reported that patients have high PRL levels compared to healthy patients [10]. Another study in 181 patients with type 1 and 2 diabetes mellitus found that diabetic subjects had higher plasma PRL levels compared to healthy subjects (32.8 ± 4 ng/mL vs. 16.3 ± 1.7 ng/mL) [75].
This increase in PRL levels in patients with T1DM has not been consistent, as other studies report a decrease in PRL in T1DM. For example, in a study of 11 patients with poorly controlled T1DM, the serum PRL concentration was found to be 5.5 ± 0.42 μg/L, which was significantly lower than the PRL concentrationin healthy individuals (9.3 ± 0.86 μg/L) [11]. In addition, other studies have found no difference in PRL concentration between patients with T1DM and healthy individuals [12, 98], [99], [100]. Treatment seems not to affect PRL concentration in patients with T1DM, as neither insulin, nor metformin affects its concentration [98, 101].
Some authors propose that alterations in PRL homeostasis, in patients with T1DM, are related to the control of secretion, so that the PRL level depends on the time at which the sample is taken. A study in 14 children with newly diagnosed T1DM found no difference in serum PRL levels compared with healthy individuals; however, when PRL release was stimulated with thyrotropin-releasing hormone (TRH), an increased response was observed [102]. In patients with T1DM it has been reported that hypoglycemia-stimulated PRL secretion is impaired, since the plasma glucose levels required to stimulate PRL release are lower in patients with well-controlled T1DM compared to patients with uncontrolled T1DM and healthy individuals [103].
Studies on PRL secretion have also been inconsistent, as a study of pulsatile and circadian PRL release patterns indicates a decrease in secreted PRL or rapid metabolic clearance in patients with diabetes, rather than an increase [11]. On the other hand, a study in 30 patients with T1DM found no change in PRL secretion upon stimulation with TRH compared to patients with type 2 diabetes mellitus and healthy individuals [104]. The heterogeneity in results is a consequence of the multiple factors that can affect PLR homeostasis such as hormones, neurotransmitters, cytokines and circadian rhythm [16, 19, 26].
The concentration of PRL in patients has also been related to the clinical manifestations of the disease. For example, diabetic patients without retinopathy have higher serum PRL levels compared to patients with retinopathy (diabetics with severe retinopathy: 26.7 ± 2.7 ng/mL and diabetics without retinopathy: 34.1 ± 3.6 ng/mL) [75]. This protective effect of PRL in retinopathy has been related to its ability to convert to vasoinhibins [75]. In addition, the serum PRL level in women with T1DM with ketoacidosis or severe ketonuria was lower compared to women with DM1 without ketoacidosis [105]. Another study in women of childbearing age with a diagnosis of T1DM showed that PRL concentration correlated negatively with HbA1c (glycosylated hemoglobin) and daily insulin dose, indicating better glycemic control in patients with higher PRL levels [106]. Thus, observational studies in patients seem to indicate that prolactin has a beneficial effect in T1DM.
Conclusions
Although several autoimmune diseases have been associated to hyperprolactinemia; howver, the studies related to PRL levels and T1DM are inconclusive, due to those results are observational and heterogenous. Conversely, studies in murine models have shown that PRL have beneficial effects on maintaining beta-cell function and protecting them from apoptosis. In addition, some studies in T1DM patients have shown that high levels of PRL correlate with better disease control. Prolactin treatment seems to be a promising strategy to improve beta-cell vascularization and proliferation in transplantation and immunotherapies. Thus, the hypothesis that high levels of PRL are detrimental in T1DM should be reconsidered. Finally, in future studies evaluating the clinical potential of PRL in T1DM it is important to consider the doses and route of administration.
Acknowledgments
Edgar Ramos-Martínez and Ivan Ramos-Martínez receive a postdoctoral fellowship from DGAPA, UNAM, México and are grateful for the funding.
-
Research funding: None declared.
-
Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.
-
Competing interests: Authors state no conflict of interest.
-
Informed consent: not applicable.
-
Ethical approval: not applicable.
References
1. Borba, VV, Zandman-Goddard, G, Shoenfeld, Y. Prolactin and autoimmunity: the hormone as an inflammatory cytokine. Best Pract Res Clin Endocrinol Metabol 2019;33:101324. https://doi.org/10.1016/j.beem.2019.101324.Search in Google Scholar PubMed
2. Jara, LJ, Medina, G, Saavedra, MA, Vera-Lastra, O, Torres-Aguilar, H, Navarro, C, et al.. Prolactin has a pathogenic role in systemic lupus erythematosus. Immunol Res 2017;65:512–23. https://doi.org/10.1007/s12026-016-8891-x.Search in Google Scholar PubMed
3. Tang, MW, Garcia, S, Gerlag, DM, Tak, PP, Reedquist, KA. Insight into the endocrine system and the immune system: a review of the inflammatory role of prolactin in rheumatoid arthritis and psoriatic arthritis. Front Immunol 2017;8:720. https://doi.org/10.3389/fimmu.2017.00720.Search in Google Scholar PubMed PubMed Central
4. Orbach, H, Shoenfeld, Y. Hyperprolactinemia and autoimmune diseases. Autoimmun Rev 2007;6:537–42. https://doi.org/10.1016/j.autrev.2006.10.005.Search in Google Scholar PubMed
5. Jara, LJ, Medina, G, Saavedra, MA, Vera-Lastra, O, Navarro, C. Prolactin and autoimmunity. Clin Rev Allergy Immunol [Internet] 2011;40:50–9. https://doi.org/10.1007/s12016-009-8185-3.Search in Google Scholar PubMed
6. Shelly, S, Boaz, M, Orbach, H. Prolactin and autoimmunity. Autoimmun Rev 2012;11:A465–70. https://doi.org/10.1016/j.autrev.2011.11.009.Search in Google Scholar PubMed
7. Solis, AMP, Rodríguez, GG, Vega, MME. Prolactin and skin autoimmunity. DermatologíaCMQ 2013;11:148–54.Search in Google Scholar
8. De Bellis, A, Bizzarro, A, Pivonello, R, Lombardi, G, Bellastella, A. Prolactin and autoimmunity. Pituitary 2005;8:25–30. https://doi.org/10.1007/s11102-005-5082-5.Search in Google Scholar PubMed
9. Cejkova, P, Fojtikova, M, Cerna, M. Immunomodulatory role of prolactin in diabetes development. Autoimmun Rev 2009;9:23–7. https://doi.org/10.1016/j.autrev.2009.02.031.Search in Google Scholar PubMed
10. Hylmarova, S, Stechova, K, Pavlinkova, G, Peknicova, J, Macek, M, Kvapil, M. The impact of type 1 diabetes mellitus on male sexual functions and sex hormone levels. Endocr J 2020;67:59–71. https://doi.org/10.1507/endocrj.ej19-0280.Search in Google Scholar PubMed
11. Iranmanesh, A, Veldhuis, JD, Carlsen, EC, Vaccaro, VA, Booth, RAJ, Lizarralde, G, et al.. Attenuated pulsatile release of prolactin in men with insulin-dependent diabetes mellitus. J Clin Endocrinol Metab 1990;71:73–8. https://doi.org/10.1210/jcem-71-1-73.Search in Google Scholar PubMed
12. Alexopoulou, O, Jamart, J, Maiter, D, Hermans, MP, De Hertogh, R, De Nayer, P, et al.. Erectile dysfunction and lower androgenicity in type 1 diabetic patients. Diabetes Metab 2001;27:329–36.Search in Google Scholar
13. Cao, Y, Feng, Z, He, X, Zhang, X, Xing, B, Wu, Y, et al.. Prolactin-regulated Pbk is involved in pregnancy-induced β cell proliferation in mice. J Endocrinol 2021;252:107–23. https://doi.org/10.1530/JOE-21-0114.Search in Google Scholar PubMed
14. Baeyens, L, Hindi, S, Sorenson, RL, German, MS. β-Cell adaptation in pregnancy. Diabetes Obes Metab 2016;18:63–70. https://doi.org/10.1111/dom.12716.Search in Google Scholar PubMed PubMed Central
15. Nardelli, TR, Vanzela, EC, Benedicto, KC, Brozzi, F, Fujita, A, Cardozo, AK, et al.. Prolactin protects against cytokine-induced beta-cell death by NFκB and JNK inhibition. J Mol Endocrinol 2018;61:25–36. https://doi.org/10.1530/jme-16-0257.Search in Google Scholar PubMed
16. Bernard, V, Young, J, Binart, N. Prolactin - a pleiotropic factor in health and disease. Nat Rev Endocrinol 2019;15:356–65. https://doi.org/10.1038/s41574-019-0194-6.Search in Google Scholar PubMed
17. Freeman, ME, Kanyicska, B, Lerant, A, Nagy, G. Prolactin: structure, function, and regulation of secretion. Physiol Rev 2000;80:1523–631. https://doi.org/10.1152/physrev.2000.80.4.1523.Search in Google Scholar PubMed
18. Costanza, M, Binart, N, Steinman, L, Pedotti, R. Prolactin: a versatile regulator of inflammation and autoimmune pathology. Autoimmun Rev 2015;14:223–30. https://doi.org/10.1016/j.autrev.2014.11.005.Search in Google Scholar PubMed
19. Marano, RJ, Ben-Jonathan, N. Minireview: extrapituitary prolactin: an update on the distribution, regulation, and functions. Mol Endocrinol 2014;28:622–33. https://doi.org/10.1210/me.2013-1349.Search in Google Scholar PubMed PubMed Central
20. Fahie-Wilson, M, Smith, TP. Determination of prolactin: the macroprolactin problem. Best Pract Res Clin Endocrinol Metabol 2013;27:725–42. https://doi.org/10.1016/j.beem.2013.07.002.Search in Google Scholar PubMed
21. Abramicheva, PA, Smirnova, OV. Prolactin receptor isoforms as the basis of tissue-specific action of prolactin in the norm and pathology. Biochem 2019;84:329–45. https://doi.org/10.1134/s0006297919040011.Search in Google Scholar PubMed
22. Trott, JF, Hovey, RC, Koduri, S, Vonderhaar, BK. Multiple new isoforms of the human prolactin receptor gene. Adv Exp Med Biol 2004;554:495–9. https://doi.org/10.1007/978-1-4757-4242-8_71.Search in Google Scholar PubMed
23. Smith, PE. The effect of hypophysectomy upon the involution of the thymus in the rat. Anat Rec 1930;47:119–29. [Internet]. https://doi.org/10.1002/ar.1090470110.Search in Google Scholar
24. Nagy, E, Berczi, I. Immunodeficiency in hypophysectomized rats. Acta Endocrinol 1978;89:530–7. https://doi.org/10.1530/acta.0.0890530.Search in Google Scholar PubMed
25. Nagy, E, Berczi, I, Wren, GE, Asa, SL, Kovacs, K. Immunomodulation by bromocriptine. Immunopharmacology 1983;6:231–43. https://doi.org/10.1016/0162-3109(83)90023-1.Search in Google Scholar PubMed
26. Ramos-Martinez, E, Ramos-Martínez, I, Molina-Salinas, G, Zepeda-Ruiz, WA, Cerbon, M. The role of prolactin in central nervous system inflammation. Rev Neurosci 2021;32:323–40. https://doi.org/10.1515/revneuro-2020-0082.Search in Google Scholar PubMed
27. Matera, L. Action of pituitary and lymphocyte prolactin. Neuroimmunomodulation 1997;4:171–80. https://doi.org/10.1159/000097335.Search in Google Scholar PubMed
28. Theas, MS, De Laurentis, A, Lasaga, M, Pisera, D, Duvilanski, BH, Seilcovich, A. Effect of lipopolysaccharide on tumor necrosis factor and prolactin release from rat anterior pituitary cells. Endocrine 1998;8:241–5. https://doi.org/10.1385/endo:8:3:241.10.1385/ENDO:8:3:241Search in Google Scholar PubMed
29. Chikanza, IC. Prolactin and neuroimmunomodulation: in vitro and in vivo observations. Ann N Y Acad Sci 1999;876:119–30. https://doi.org/10.1111/j.1749-6632.1999.tb07629.x.Search in Google Scholar PubMed
30. Pellegrini, I, Lebrun, JJ, Ali, S, Kelly, PA. Expression of prolactin and its receptor in human lymphoid cells. Mol Endocrinol 1992;6:1023–31. https://doi.org/10.1210/mend.6.7.1508218.Search in Google Scholar PubMed
31. Gerlo, S, Verdood, P, Hooghe-Peters, EL, Kooijman, R. Modulation of prolactin expression in human T lymphocytes by cytokines. J Neuroimmunol 2005;162:190–3. https://doi.org/10.1016/j.jneuroim.2005.02.008.Search in Google Scholar PubMed
32. Díaz, L, Martínez-Reza, I, García-Becerra, R, González, L, Larrea, F, Méndez, I. Calcitriol stimulates prolactin expression in non-activated human peripheral blood mononuclear cells: breaking paradigms. Cytokine 2011;55:188–94. https://doi.org/10.1016/j.cyto.2011.04.013.Search in Google Scholar PubMed
33. Savino, W. Prolactin: an immunomodulator in health and disease. Front Horm Res 2017;48:69–75. https://doi.org/10.1159/000452906.Search in Google Scholar PubMed
34. Carreño, PC, Sacedón, R, Jiménez, E, Vicente, A, Zapata, AG. Prolactin affects both survival and differentiation of T-cell progenitors. J Neuroimmunol 2005;160:135–45. https://doi.org/10.1016/j.jneuroim.2004.11.008.Search in Google Scholar PubMed
35. Montes de Oca, P, Macotela, Y, Nava, G, López-Barrera, F, de la Escalera, GM, Clapp, C. Prolactin stimulates integrin-mediated adhesion of circulating mononuclear cells to endothelial cells. Lab Invest 2005;85:633–42. https://doi.org/10.1038/labinvest.3700256.Search in Google Scholar PubMed
36. Legorreta-Haquet, MV, Chávez-Rueda, K, Montoya-Díaz, E, Arriaga-Pizano, L, Silva-García, R, Chávez-Sánchez, L, et al.. Prolactin down-regulates CD4+CD25hiCD127low/- regulatory T cell function in humans. J Mol Endocrinol 2012;48:77–85. https://doi.org/10.1530/jme-11-0040.Search in Google Scholar PubMed
37. Chavez-Rueda, K, Hérnández, J, Zenteno, E, Leaños-Miranda, A, Legorreta-Haquet, MV, Blanco-Favela, F. Identification of prolactin as a novel immunomodulator on the expression of co-stimulatory molecules and cytokine secretions on T and B human lymphocytes. Clin Immunol 2005;116:182–91. https://doi.org/10.1016/j.clim.2005.03.013.Search in Google Scholar PubMed
38. Takizawa, K, Kitani, S, Takeuchi, F, Yamamoto, K. Enhanced expression of CD69 and CD25 antigen on human peripheral blood mononuclear cells by prolactin. Endocr J 2005;52:635–41. https://doi.org/10.1507/endocrj.52.635.Search in Google Scholar PubMed
39. Legorreta-Herrera, M. The influence of prolactin on the immune response to parasitic diseases. Adv Neuroimmune Biol 2018;7:107–14. https://doi.org/10.3233/nib-170131.Search in Google Scholar
40. Matalka, KZ. Prolactin enhances production of interferon-gamma, interleukin-12, and interleukin-10, but not of tumor necrosis factor-alpha, in a stimulus-specific manner. Cytokine 2003;21:187–94. https://doi.org/10.1016/s1043-4666(02)00496-9.Search in Google Scholar PubMed
41. Carreño, PC, Jiménez, E, Sacedón, R, Vicente, A, Zapata, AG. Prolactin stimulates maturation and function of rat thymic dendritic cells. J Neuroimmunol 2004;153:83–90. https://doi.org/10.1016/j.jneuroim.2004.04.020.Search in Google Scholar PubMed
42. Brand, JM, Frohn, C, Cziupka, K, Brockmann, C, Kirchner, H, Luhm, J. Prolactin triggers pro-inflammatory immune responses in peripheral immune cells. Eur Cytokine Netw 2004;15:99–104.Search in Google Scholar
43. Zaga-Clavellina, V, Parra-Covarrubias, A, Ramirez-Peredo, J, Vega-Sanchez, R, Vadillo-Ortega, F. The potential role of prolactin as a modulator of the secretion of proinflammatory mediators in chorioamniotic membranes in term human gestation. Am J Obstet Gynecol 2014;211:48.e1–6. https://doi.org/10.1016/j.ajog.2014.01.039.Search in Google Scholar PubMed
44. Olmos-Ortiz, A, Déciga-García, M, Preciado-Martínez, E, Bermejo-Martínez, L, Flores-Espinosa, P, Mancilla-Herrera, I, et al.. Prolactin decreases LPS-induced inflammatory cytokines by inhibiting TLR-4/NFκB signaling in the human placenta. Mol Hum Reprod 2019;25:660–7. https://doi.org/10.1093/molehr/gaz038.Search in Google Scholar PubMed PubMed Central
45. Arnold, E, Thebault, S, Baeza-Cruz, G, Arredondo Zamarripa, D, Adán, N, Quintanar-Stéphano, A, et al.. The hormone prolactin is a novel, endogenous trophic factor able to regulate reactive glia and to limit retinal degeneration. J Neurosci 2014;34:1868–78. https://doi.org/10.1523/jneurosci.2452-13.2014.Search in Google Scholar
46. Cabrera-Reyes, EA, Vanoye-Carlo, A, Rodríguez-Dorantes, M, Vázquez-Martínez, ER, Rivero-Segura, NA, Collazo-Navarrete, O, et al.. Transcriptomic analysis reveals new hippocampal gene networks induced by prolactin. Sci Rep 2019;9:13765. https://doi.org/10.1038/s41598-019-50228-7.Search in Google Scholar PubMed PubMed Central
47. Corbacho, AM, Macotela, Y, Nava, G, Eiserich, JP, Cross, CE, Martínez de la Escalera, G, et al.. Cytokine induction of prolactin receptors mediates prolactin inhibition of nitric oxide synthesis in pulmonary fibroblasts. FEBS Lett 2003;544:171–5. https://doi.org/10.1016/s0014-5793(03)00499-x.Search in Google Scholar PubMed
48. Gutiérrez-Barroso, A, Anaya-López, JL, Lara-Zárate, L, Loeza-Lara, PD, López-Meza, JE, Ochoa-Zarzosa, A. Prolactin stimulates the internalization of Staphylococcus aureus and modulates the expression of inflammatory response genes in bovine mammary epithelial cells. Vet Immunol Immunopathol 2008;121:113–22. https://doi.org/10.1016/j.vetimm.2007.09.007.Search in Google Scholar PubMed
49. Martínez-Neri, PA, López-Rincón, G, Mancilla-Jiménez, R, del Toro-Arreola, S, Muñoz-Valle, JF, Fafutis-Morris, M, et al.. Prolactin modulates cytokine production induced by culture filtrate proteins of M. bovis through different signaling mechanisms in THP1 cells. Cytokine 2015;71:38–44. https://doi.org/10.1016/j.cyto.2014.08.006.Search in Google Scholar PubMed
50. Shrivastava, V, Lee, M, Lee, D, Pretorius, M, Radford, B, Makkar, G, et al.. Beta cell adaptation to pregnancy requires prolactin action on both beta and non-beta cells. Sci Rep 2021;11:10372. https://doi.org/10.1038/s41598-021-89745-9.Search in Google Scholar PubMed PubMed Central
51. Ramirez-Hernandez, G, Adan-Castro, E, Diaz-Lezama, N, Ruiz-Herrera, X, Martinez de la Escalera, G, Macotela, Y, et al.. Global deletion of the prolactin receptor aggravates streptozotocin-induced diabetes in mice. Front Endocrinol 2021;12:619696. https://doi.org/10.3389/fendo.2021.619696.Search in Google Scholar PubMed PubMed Central
52. Raisova, M, Hossini, AM, Eberle, J, Riebeling, C, Orfanos, CE, Geilen, CC, et al.. The bax/bcl-2 ratio determines the susceptibility of human melanoma cells to CD95/fas-mediated apoptosis. J Invest Dermatol 2001;117:333–40. https://doi.org/10.1046/j.0022-202x.2001.01409.x.Search in Google Scholar PubMed
53. Terra, LF, Garay-Malpartida, MH, Wailemann, RAM, Sogayar, MC, Labriola, L. Recombinant human prolactin promotes human beta cell survival via inhibition of extrinsic and intrinsic apoptosis pathways. Diabetologia 2011;54:1388–97. https://doi.org/10.1007/s00125-011-2102-z.Search in Google Scholar PubMed
54. Terra, LF, Wailemann, RAM, Dos Santos, AF, Gomes, VM, Silva, RP, Laporte, A, et al.. Heat shock protein B1 is a key mediator of prolactin-induced beta-cell cytoprotection against oxidative stress. Free Radic Biol Med 2019;134:394–405. https://doi.org/10.1016/j.freeradbiomed.2019.01.023.Search in Google Scholar PubMed
55. Gomes, VM, Wailemann, RAM, Arini, GS, Oliveira, TC, Almeida, DRQ, Dos Santos, AF, et al.. HSPB1 is essential for inducing resistance to proteotoxic stress in beta-cells. Cells 2021;10:2178. https://doi.org/10.3390/cells10092178.Search in Google Scholar PubMed PubMed Central
56. Mule, SN, Gomes, VDM, Wailemann, RAM, Macedo-da-Silva, J, Rosa-Fernandes, L, Larsen, MR, et al.. HSPB1 influences mitochondrial respiration in ER-stressed beta cells. Biochim Biophys Acta, Proteins Proteomics 2021;1869:140680. https://doi.org/10.1016/j.bbapap.2021.140680.Search in Google Scholar PubMed
57. Jackerott, M, Møldrup, A, Thams, P, Galsgaard, ED, Knudsen, J, Lee, YC, et al.. STAT5 activity in pancreatic beta-cells influences the severity of diabetes in animal models of type 1 and 2 diabetes. Diabetes 2006;55:2705–12. https://doi.org/10.2337/db06-0244.Search in Google Scholar PubMed
58. Xu, Y, Wang, X, Gao, L, Zhu, J, Zhang, H, Shi, H, et al.. Prolactin-stimulated survivin induction is required for beta cell mass expansion during pregnancy in mice. Diabetologia 2015;58:2064–73. https://doi.org/10.1007/s00125-015-3670-0.Search in Google Scholar PubMed
59. Hügl, SR, Merger, M. Prolactin stimulates proliferation of the glucose-dependent beta-cell line INS-1 via different IRS-proteins. JOP 2007;8:739–52.Search in Google Scholar
60. Gahr, S, Merger, M, Bollheimer, LC, Hammerschmied, CG, Schölmerich, J, Hügl, SR. Hepatocyte growth factor stimulates proliferation of pancreatic beta-cells particularly in the presence of subphysiological glucose concentrations. J Mol Endocrinol 2002;28:99–110. https://doi.org/10.1677/jme.0.0280099.Search in Google Scholar PubMed
61. Cousin, SP, Hügl, SR, Myers, MGJ, White, MF, Reifel-Miller, A, Rhodes, CJ. Stimulation of pancreatic beta-cell proliferation by growth hormone is glucose-dependent: signal transduction via janus kinase 2 (JAK2)/signal transducer and activator of transcription 5 (STAT5) with no crosstalk to insulin receptor substrate-mediated mitogenic signalling. Biochem J 1999;344 Pt 3:649–58. https://doi.org/10.1042/bj3440649.Search in Google Scholar
62. Goyvaerts, L, Schraenen, A, Schuit, F. Serotonin competence of mouse beta cells during pregnancy. Diabetologia 2016;59:1356–63. https://doi.org/10.1007/s00125-016-3951-2.Search in Google Scholar PubMed
63. Moon, JH, Kim, H, Kim, H, Park, J, Choi, W, Choi, W, et al.. Lactation improves pancreatic β cell mass and function through serotonin production. Sci Transl Med 2020;12:eaay0455. https://doi.org/10.1126/scitranslmed.aay0455.Search in Google Scholar PubMed PubMed Central
64. Kim, H, Toyofuku, Y, Lynn, FC, Chak, E, Uchida, T, Mizukami, H, et al.. Serotonin regulates pancreatic beta cell mass during pregnancy. Nat Med 2010;16:804–8. https://doi.org/10.1038/nm.2173.Search in Google Scholar PubMed PubMed Central
65. Sorenson, RL, Brelje, TC. Adaptation of islets of Langerhans to pregnancy: beta-cell growth, enhanced insulin secretion and the role of lactogenic hormones. Horm Metab Res = Horm und Stoffwechselforsch = Horm Metab 1997;29:301–7. https://doi.org/10.1055/s-2007-979040.Search in Google Scholar PubMed
66. Strutt, B, Szlapinski, S, Gnaneswaran, T, Donegan, S, Hill, J, Bennett, J, et al.. Ontology of the apelinergic system in mouse pancreas during pregnancy and relationship with β-cell mass. Sci Rep 2021;11:15475. https://doi.org/10.1038/s41598-021-94725-0.Search in Google Scholar PubMed PubMed Central
67. Huang, C, Snider, F, Cross, JC. Prolactin receptor is required for normal glucose homeostasis and modulation of beta-cell mass during pregnancy. Endocrinology 2009;150:1618–26. https://doi.org/10.1210/en.2008-1003.Search in Google Scholar PubMed
68. Johansson, M, Olerud, J, Jansson, L, Carlsson, PO. Prolactin treatment improves engraftment and function of transplanted pancreatic islets. Endocrinology 2009;150:1646–53. https://doi.org/10.1210/en.2008-1318.Search in Google Scholar PubMed
69. Yang, X, Friedl, A. A positive feedback loop between prolactin and STAT5 promotes angiogenesis. Adv Exp Med Biol 2015;846:265–80. https://doi.org/10.1007/978-3-319-12114-7_12.Search in Google Scholar PubMed
70. Yang, X, Meyer, K, Friedl, A. STAT5 and prolactin participate in a positive autocrine feedback loop that promotes angiogenesis. J Biol Chem 2013;288:21184–96. https://doi.org/10.1074/jbc.m113.481119.Search in Google Scholar
71. Clapp, C, Thebault, S, Martínez de la Escalera, G. Role of prolactin and vasoinhibins in the regulation of vascular function in mammary gland. J Mammary Gland Biol Neoplasia 2008;13:55–67. https://doi.org/10.1007/s10911-008-9067-7.Search in Google Scholar PubMed
72. Clapp, C, Thebault, S, Jeziorski, MC, Martínez De La Escalera, G. Peptide hormone regulation of angiogenesis. Physiol Rev 2009;89:1177–215. https://doi.org/10.1152/physrev.00024.2009.Search in Google Scholar PubMed
73. Clapp, C, Thebault, S, Macotela, Y, Moreno-Carranza, B, Triebel, J, Martínez de la Escalera, G. Regulation of blood vessels by prolactin and vasoinhibins. Adv Exp Med Biol 2015;846:83–95. https://doi.org/10.1007/978-3-319-12114-7_4.Search in Google Scholar PubMed
74. Triebel, J, Bertsch, T, Bollheimer, C, Rios-Barrera, D, Pearce, CF, Hüfner, M, et al.. Principles of the prolactin/vasoinhibin axis. Am J Physiol Regul Integr Comp Physiol 2015;309:R1193–203. https://doi.org/10.1152/ajpregu.00256.2015.Search in Google Scholar PubMed PubMed Central
75. Arnold, E, Rivera, JC, Thebault, S, Moreno-Páramo, D, Quiroz-Mercado, H, Quintanar-Stéphano, A, et al.. High levels of serum prolactin protect against diabetic retinopathy by increasing ocular vasoinhibins. Diabetes 2010;59:3192–7. https://doi.org/10.2337/db10-0873.Search in Google Scholar PubMed PubMed Central
76. Rewers, M, Ludvigsson, J. Environmental risk factors for type 1 diabetes. Lancet (London, England) 2016;387:2340–8. https://doi.org/10.1016/s0140-6736(16)30507-4.Search in Google Scholar PubMed PubMed Central
77. Norris, JM, Johnson, RK, Stene, LC. Type 1 diabetes-early life origins and changing epidemiology. Lancet Diabetes Endocrinol 2020;8:226–38. https://doi.org/10.1016/s2213-8587(19)30412-7.Search in Google Scholar
78. Roep, BO, Thomaidou, S, van Tienhoven, R, Zaldumbide, A. Type 1 diabetes mellitus as a disease of the β-cell (do not blame the immune system?). Nat Rev Endocrinol 2021;17:150–61. https://doi.org/10.1038/s41574-020-00443-4.Search in Google Scholar PubMed PubMed Central
79. Barrett, JC, Clayton, DG, Concannon, P, Akolkar, B, Cooper, JD, Erlich, HA, et al.. Genome-wide association study and meta-analysis find that over 40 loci affect risk of type 1 diabetes. Nat Genet 2009;41:703–7. https://doi.org/10.1038/ng.381.Search in Google Scholar PubMed PubMed Central
80. van Lummel, M, van Veelen, PA, de Ru, AH, Pool, J, Nikolic, T, Laban, S, et al.. Discovery of a selective islet peptidome presented by the highest-risk HLA-DQ8trans molecule. Diabetes 2016;65:732–41. https://doi.org/10.2337/db15-1031.Search in Google Scholar PubMed
81. Michels, AW, Landry, LG, McDaniel, KA, Yu, L, Campbell-Thompson, M, Kwok, WW, et al.. Islet-derived CD4 T cells targeting proinsulin in human autoimmune diabetes. Diabetes 2017;66:722–34. https://doi.org/10.2337/db16-1025.Search in Google Scholar PubMed PubMed Central
82. Lindley, S, Dayan, CM, Bishop, A, Roep, BO, Peakman, M, Tree, TIM. Defective suppressor function in CD4(+)CD25(+) T-cells from patients with type 1 diabetes. Diabetes 2005;54:92–9. https://doi.org/10.2337/diabetes.54.1.92.Search in Google Scholar PubMed
83. Smith, MJ, Simmons, KM, Cambier, JC. B cells in type 1 diabetes mellitus and diabetic kidney disease. Nat Rev Nephrol 2017;13:712–20. https://doi.org/10.1038/nrneph.2017.138.Search in Google Scholar PubMed PubMed Central
84. Hinman, RM, Cambier, JC. Role of B lymphocytes in the pathogenesis of type 1 diabetes. Curr Diabetes Rep 2014;14:543. https://doi.org/10.1007/s11892-014-0543-8.Search in Google Scholar PubMed
85. Hu, C, Rodriguez-Pinto, D, Du, W, Ahuja, A, Henegariu, O, Wong, FS, et al.. Treatment with CD20-specific antibody prevents and reverses autoimmune diabetes in mice. J Clin Invest 2007;117:3857–67. https://doi.org/10.1172/jci32405.Search in Google Scholar
86. McMurray, RW. Bromocriptine in rheumatic and autoimmune diseases. Semin Arthritis Rheum 2001;31:21–32. https://doi.org/10.1053/sarh.2001.25482.Search in Google Scholar PubMed
87. Walker, SE. Treatment of systemic lupus erythematosus with bromocriptine. Lupus 2001;10:197–202. https://doi.org/10.1191/096120301666625458.Search in Google Scholar PubMed
88. Hawkins, TA, Gala, RR, Dunbar, JC. Prolactin modulates the incidence of diabetes in male and female NOD mice. Autoimmunity 1994;18:155–62. https://doi.org/10.3109/08916939409007991.Search in Google Scholar PubMed
89. Durant, S, Alves, V, Coulaud, J, El Hasnaoui, A, Dardenne, M, Homo-Delarche, F. Attempts to pharmacologically modulate prolactin levels and type 1 autoimmune diabetes in the non-obese diabetic (NOD) mouse. J Autoimmun 1995;8:875–85. https://doi.org/10.1016/s0896-8411(95)80023-9.Search in Google Scholar PubMed
90. Durant, S, Coulaud, J, Homo-Delarche, F. Bromocriptine-induced hyperglycemia in nonobese diabetic mice: kinetics and mechanisms of action. Rev Diabet Stud 2007;4:185–94. https://doi.org/10.1900/rds.2007.4.185.Search in Google Scholar PubMed PubMed Central
91. Lehtovirta, P, Ranta, T. Effect of short-term bromocriptine treatment on amniotic fluid prolactin concentration in the first half of pregnancy. Acta Endocrinol 1981;97:559–61. https://doi.org/10.1530/acta.0.0970559.Search in Google Scholar PubMed
92. Golander, A, Barrett, J, Hurley, T, Barry, S, Handwerger, S. Failure of bromocriptine, dopamine, and thyrotropin-releasing hormone to affect prolactin secretion by human decidual tissue in vitro. J Clin Endocrinol Metab 1979;49:787–9. https://doi.org/10.1210/jcem-49-5-787.Search in Google Scholar PubMed
93. Holstad, M, Sandler, S. Prolactin protects against diabetes induced by multiple low doses of streptozotocin in mice. J Endocrinol 1999;163:229–34. https://doi.org/10.1677/joe.0.1630229.Search in Google Scholar PubMed
94. Lau, J, Börjesson, A, Holstad, M, Sandler, S. Prolactin regulation of the expression of TNF-alpha, IFN-gamma and IL-10 by splenocytes in murine multiple low dose streptozotocin diabetes. Immunol Lett 2006;102:25–30. https://doi.org/10.1016/j.imlet.2005.06.006.Search in Google Scholar PubMed
95. Fourcade, G, Colombo, BM, Grégoire, S, Baeyens, A, Rachdi, L, Guez, F, et al.. Fetal pancreas transplants are dependent on prolactin for their development and prevent type 1 diabetes in syngeneic but not allogeneic mice. Diabetes 2013;62:1646–55. https://doi.org/10.2337/db12-0448.Search in Google Scholar PubMed PubMed Central
96. Hyslop, CM, Tsai, S, Shrivastava, V, Santamaria, P, Huang, C. Prolactin as an adjunct for type 1 diabetes immunotherapy. Endocrinology 2016;157:150–65. https://doi.org/10.1210/en.2015-1549.Search in Google Scholar PubMed
97. Park, S, Kim, DS, Daily, JW, Kim, SH. Serum prolactin concentrations determine whether they improve or impair β-cell function and insulin sensitivity in diabetic rats. Diabetes Metab Res Rev 2011;27:564–74. https://doi.org/10.1002/dmrr.1215.Search in Google Scholar PubMed
98. Frier, BM, Fisher, BM, Gray, CE, Beastall, GH. Counterregulatory hormonal responses to hypoglycaemia in type 1 (insulin-dependent) diabetes: evidence for diminished hypothalamic-pituitary hormonal secretion. Diabetologia 1988;31:421–9. https://doi.org/10.1007/bf00271586.Search in Google Scholar PubMed
99. Ostrom, KM, Ferris, AM. Prolactin concentrations in serum and milk of mothers with and without insulin-dependent diabetes mellitus. Am J Clin Nutr 1993;58:49–53. https://doi.org/10.1093/ajcn/58.1.49.Search in Google Scholar PubMed
100. Zukowska-Szczechowska, E, Moczulski, D, Grzeszczak, W, Gumprecht, J. [Prolactin secretion in diabetic nephropathy of patients with diabetes mellitus type I (IDDM)]. Pol Arch Med Wewn 1996;95:125–34.Search in Google Scholar
101. Hafez, M, Musa, N, Elbehairy, S, Atty, SA, Elbarbary, M, Amin, M. Effect of metformin on clinical and biochemical hyperandrogenism in adolescent girls with type 1 diabetes. J Pediatr Endocrinol Metab 2019;32:461–70. https://doi.org/10.1515/jpem-2018-0430.Search in Google Scholar PubMed
102. Abe, K, Matsuura, N, Fukushima, N, Nohara, Y, Fujita, H, Fujieda, K, et al.. Plasma prolactin response to thyrotropin releasing hormone in children with newly diagnosed insulin dependent diabetes. Tohoku J Exp Med 1983;140:29–34. https://doi.org/10.1620/tjem.140.29.Search in Google Scholar PubMed
103. Kinsley, BT, Levy, CJ, Simonson, DC. Prolactin and beta-endorphin responses to hypoglycemia are reduced in well-controlled insulin-dependent diabetes mellitus. Metabolism 1996;45:1434–40. https://doi.org/10.1016/s0026-0495(96)90127-4.Search in Google Scholar PubMed
104. Orlická, E, Vondra, K, Hill, M, Skibová, J, Sterzl, I, Zamrazil, V. TRH test in patients with diabetes mellitus type 1 and/or autoimmune thyroiditis. Changes in the pituitary-thyroid axis, reverse T3, prolactin and growth hormone levels. Physiol Res 2008;57(1 Suppl):S109–17. https://doi.org/10.33549/physiolres.931495.Search in Google Scholar PubMed
105. Välimäki, M, Liewendahl, K, Nikkanen, P, Pelkonen, R. Hormonal changes in severely uncontrolled type 1 (insulin-dependent) diabetes mellitus. Scand J Clin Lab Invest 1991;51:385–93. https://doi.org/10.3109/00365519109091630.Search in Google Scholar PubMed
106. Kvasnickova, H, Hampl, R, Vondra, K. DHEA, DHEAS and prolactin correlate with glucose control parameters in women of fertile age with type-1 diabetes mellitus. Physiol Res 2015;64(2 Suppl):S255–8. https://doi.org/10.33549/physiolres.933091.Search in Google Scholar PubMed
© 2022 the author(s), published by De Gruyter, Berlin/Boston
This work is licensed under the Creative Commons Attribution 4.0 International License.
