Immunodeficiency in Hypophysectomized Rats

Nagy, Éva; Berczi, István

doi:10.1530/acta.0.0890530

Cited by 187 publications

(58 citation statements)

References 11 publications

(15 reference statements)

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“…In viva bromocriptine pretreatment inhibited splenic lymphocyte proliferative responses in vitro to the immunizing antigen and to concanavalin A. Moreover, bromocriptine therapy was protective when initiated 1 week after the initial immunization and w a s also effective in suppression of late disease. These results indicate that (1) prolactin levels are elevated after immunization and before the onset of experimental allergic encephalomyelitis, (2) bromocriptine inhibits both prolactin secretion and the severity of acute experimental allergic encephalomyelitis, and (3) inhibition is also present when treatment is begun after sensitization, suggesting an effect of prolactin on the effector limb of the immune response during experimental allergic encephalomyelitis.…”

mentioning

confidence: 96%

The role of prolactin in autoimmune demyelination: Suppression of experimental allergic encephalomyelitis by bromocriptine

Riskind

Massacesi

Doolittle

et al. 1991

Annals of Neurology

108

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Several lines of evidence suggest that the anterior pituitary hormone prolactin has a stimulatory roIe on immune function and that pharmacological suppression of prolactin secretion with the dopamine-agonist bromocriptine suppresses both humoral and cellular immunity. Here, we describe the effects of prolactin-suppression on the course of experimental allergic encephalomyelitis in female Lewis rats. Initiation of continuous bromocriptine treatment before immunization reduced both the severity and incidence of clinical signs of acute experimental allergic encephalomyelitis. Experimental allergic encephalomyelitis-immunized rats experienced a threefold rise in basal prolactin levels on day 4 after immunization and maintained elevated prolactin levels on day 10, before the onset of neurological signs of experimental allergic encephalomyelitis. Bromocriptine treatment reduced prolactin levels to those of shamimmunized rats. In viva bromocriptine pretreatment inhibited splenic lymphocyte proliferative responses in vitro to the immunizing antigen and to concanavalin A. Moreover, bromocriptine therapy was protective when initiated 1 week after the initial immunization and w a s also effective in suppression of late disease. These results indicate that (1) prolactin levels are elevated after immunization and before the onset of experimental allergic encephalomyelitis, (2) bromocriptine inhibits both prolactin secretion and the severity of acute experimental allergic encephalomyelitis, and (3) inhibition is also present when treatment is begun after sensitization, suggesting an effect of prolactin on the effector limb of the immune response during experimental allergic encephalomyelitis.Riskind PN, Massacesi L, Doolittle TH, Hauser SL. The role of prolactin in autoimmune demyelination: suppression of experimental allergic encephaiomyelitis by bromocriptine. Ann Neurol 199 1; Prolactin (PRL), the major hormonal stimulus to lactation, is a 24-kd polypeptide hormone that is synthesized and secreted by the anterior pituitary gland. The importance of PRL to normal immune homeostasis was first shown by Nagy and Berczi 111, who found that hypophysectomized rats were severely immunocompromised, with profoundly depressed antibody titers to administered antigen and virtually absent delayed hypersensitivity responses. Surprisingly, in such animals, immunocompetence could be restored by exogenous PRL, and to a lesser extent by growth hormone, but not by other pituitary hormones 121. Later work demonstrated that bromocriptine (BCR), a dopaminergic agonist that selectively inhibits PRL release, mimics the effect of hypophysectomy {33. Treatment with PRL reversed the effect of BCR, indicating that its activity was due to specific inhibition of PRL release.Other studies indicated that excessive PRL levels maj7 stimulate immune responses. PRL treatment of normal mice resulted in a dose-dependent increase in splenic cell responses to mitogens such as concanavalin A (ConA) [4, S}. In rodent splenic lymphocytes, PRL also induced the expres...

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confidence: 96%

The role of prolactin in autoimmune demyelination: Suppression of experimental allergic encephalomyelitis by bromocriptine

Riskind

Massacesi

Doolittle

et al. 1991

Annals of Neurology

108

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“…In animals, hypophysectomy results in cessation of the growth of the thymus gland (1), decreased antibody titers against sheep red blood cells, and depressed delayed hypersensitivity reaction to chlorodinitrobenzene (2). Bromocryptine-induced hypoprolactinemia in mice injected with Listeria monocytogenes increases mortality that is associated with impaired lymphocyte proliferation and decreased production of macrophage-activating factors by T lymphocytes (3).…”

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confidence: 99%

Prolactin synthesized and secreted by human peripheral blood mononuclear cells: an autocrine growth factor for lymphoproliferation.

Sabharwal

Glaser

Lafuse

et al. 1992

Proc. Natl. Acad. Sci. U.S.A.

195

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Prolactin has been shown to have an immunoregulatory role in the rodent immune response. A prolactinlike molecule has also been found in mouse splenocytes and a human B-lymphoblastoid cell line. We have evaluated whether human peripheral blood mononuclear cells (PBMCs) synthesize and/or secrete prolactin. We used the polymerase chain reaction (PCR) to generate a 276-base-pair prolactin product from human PBMCs, and Southern blot analysis confirmed that it was related to prolactin. Western blotting using a polyclonal antibody to prolactin indicated that cell extracts prepared from human PBMCs contained a high molecular mass (60-kDa) immunoreactive prolactin. To determine whether this PBMC prolactin was being secreted, we developed a highly sensitive and specific hormonal enzyme-linked immunoplaque assay. With this assay, we were able to detect human prolactin secretion from concanavalin A (Con A)-or phytohemagglutinin-stimulated PBMCs but not from unstimulated PBMCs. We next sought to determine whether this secreted prolactin could function as an autocrine growth factor in lymphoproliferation. We observed that anti-human prolactin antiserum significanly inhibited human PBMC proliferation in response to Con A or phytohemagglutinin. We conclude that a prolactin-like molecule is synthesized and secreted by human PBMCs and that it functions in an autocrine manner as a growth factor for lymphoproliferation.Recent studies suggest an immunoregulatory role for prolactin in rodents. In animals, hypophysectomy results in cessation of the growth of the thymus gland (1), decreased antibody titers against sheep red blood cells, and depressed delayed hypersensitivity reaction to chlorodinitrobenzene (2). Bromocryptine-induced hypoprolactinemia in mice injected with Listeria monocytogenes increases mortality that is associated with impaired lymphocyte proliferation and decreased production of macrophage-activating factors by T lymphocytes (3). Further, a prolactin-like molecule is secreted following Con A stimulation of murine lymphocytes (4), and a prolactin-like mRNA as well as a secreted product have been detected in human B-lymphoblastoid cell lines (5, 6). In contrast, Clevenger et al. (7) could not demonstrate prolactin-specific mRNA or prolactin secretion following interleukin 2 stimulation of a mouse T-lymphocyte line.Several investigators (7-9) using rodent lymphoid cell lines or splenocytes have found that a prolactin-like protein is required for lymphocyte mitogenesis. The relevance of these observations to human cellular immunity has not been explored. Here we document that human peripheral blood mononuclear cells (PBMCs) synthesize and secrete a prolactin-like molecule that functions in an autocrine loop as a growth factor for lymphoproliferation. MATERIALS AND METHODSOligonucleotide Primer Design. The sequences and positions of the two 21-mer primers used for PCR amplification of human prolactin cDNA are shown in Fig. 1 (10). The 5' primer is located within exon 3 of the human prolactin gene and the 3' pri...

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“…For example, both decreased antibody production and depressed cell mediated immunity have been observed in hypophysectomized rats (Nagy and Berczi, 1978). Similarly, immunosuppression has been observed after the administration of bromocriptine, which decreases the circulating levels of PRL to nonhypophysectomized rats.…”

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confidence: 96%

Prolactin receptor gene expression in rat splenocytes and thymocytes from birth to adulthood

Güneş

Mastro

1996

Molecular and Cellular Endocrinology

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In vivo and in vitro studies have indicated that the anterior pituitary hormone prolactin (PRL) is an immunoregulator and functions in the development of the neonatal immune system. In this study, prolactin receptor (PRL-R) expression from birth to adulthood as well as the effect of milk ingestion on the PRL-R expression were examined in splenocytes and thymocytes of neonatal rats. Three approaches were taken to measure PRL-R expression: (i) polymerase chain reaction (RT-PCR); (ii) antibody to PRL-R and Western blotting; (iii) antibody to PRL-R and flow cytometry. RT-PCR analysis revealed the short and long form of PRL-R mRNA in both spleen and thymus at every age tested. However, the long form of PRL-R mRNA was always more abundant than that of the short form. In addition, antipeptide antibody against the long form of PRL-R recognized 84 and 42 kD proteins in the spleen, but only the 84 kD protein in the thymus. A monoclonal antibody U6 recognized 38 and 40 kD proteins in both the spleen and thymus. Although the mRNA level of PRL-R was relatively low at birth and increased with age in both the spleen and thymus, the levels of protein bands detected with both antibodies correlated with development in the spleen; whereas the levels remained steady in the thymus. Therefore, we concluded that the expression of PRL-R at the protein level is developmentally regulated in the spleen but not in the thymus. Finally. milk ingestion in the first seven hours decreased the percentage of cells expressing cell surface PRL-R, suggesting that milk-borne PRL may have a direct effect on lymphocytes.

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Immunodeficiency in Hypophysectomized Rats

Cited by 187 publications

References 11 publications

The role of prolactin in autoimmune demyelination: Suppression of experimental allergic encephalomyelitis by bromocriptine

The role of prolactin in autoimmune demyelination: Suppression of experimental allergic encephalomyelitis by bromocriptine

Prolactin synthesized and secreted by human peripheral blood mononuclear cells: an autocrine growth factor for lymphoproliferation.

Prolactin receptor gene expression in rat splenocytes and thymocytes from birth to adulthood

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