RESUMO
Prolactin (PRL) is a 23 kDa protein hormone that is produced and secreted by the pituitary lactotrophs. Although PRL was initially regarded as an exclusive pituitary hormone, many nonpituitary tissues were later found to contain and produce this hormone. The most established extrapituitary sites that produce PRL are the decidua, the immune system, brain and endometrium. In the immune system, PRL acts as a cytokine where it plays an important role in human immune responses, including in autoimmune diseases. Here, we will discuss the regulation of PRL gene expression in human lymphocytes and review the functions of PRL made by the immune cells, including its involvement in autoimmunity.
Assuntos
Sistema Imunitário/fisiologia , Prolactina/fisiologia , Animais , Comunicação Autócrina , Doenças Autoimunes/metabolismo , Autoimunidade/fisiologia , Diferenciação Celular/fisiologia , Modelos Animais de Doenças , Feminino , Regulação da Expressão Gênica , Humanos , Leucócitos/metabolismo , Lúpus Eritematoso Sistêmico/metabolismo , Linfócitos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos NZB , Comunicação Parácrina , Adeno-Hipófise/metabolismo , Prolactina/genética , Regiões Promotoras Genéticas/genética , Receptores de Citocinas/fisiologia , Receptores da Prolactina/metabolismo , Transcrição GênicaRESUMO
Prolactin (PRL) Is a 23 κDa protein hormone that is produced and secreted by the pituitary lactotrophs. Although PRL was initially regarded as an exclusive pituitary hormone, many nonpituitary tissues were later found to contain and produce this hormone. The most established extrapituitary sites that produce PRL are the decidua, the immune system, brain and endometrium. In the immune system, PRL acts as a cytokine where it plays an important role in human immune responses, including in autoimmune diseases. Here, we will discuss the regulation of PRL gene expression in human lymphocytes and review the functions of PRL made by the immune cells, including its involvement in autoimmunity.
La prolactina es una hormona que fue considerada durante mucho tiempo de origen exclusivamente hipofisario, y cuya función más importante era la promoción de la lactancia. Sin embargo, la prolactina no sólo se sintetiza en diversos sitios del organismo, sino que también participa en una amplia variedad de procesos biológicos. Dentro de los sitios de síntesis extrahipofisarios de esta hormona se encuentran diversas células del sistema inmunológico. A este nivel, la prolactina actúa afectando desde la proliferación celular hasta el estado inmune del individuo. En esta revisión presentamos algunos aspectos relativos a la prolactina de origen linfocitario tales como su síntesis, su participación en el sistema inmunológico y su relación con estados de autoinmunidad.
Assuntos
Animais , Feminino , Humanos , Masculino , Camundongos , Sistema Imunitário/fisiologia , Prolactina/fisiologia , Comunicação Autócrina , Doenças Autoimunes/metabolismo , Autoimunidade/fisiologia , Diferenciação Celular/fisiologia , Modelos Animais de Doenças , Regulação da Expressão Gênica , Leucócitos/metabolismo , Lúpus Eritematoso Sistêmico/metabolismo , Linfócitos/metabolismo , Camundongos Endogâmicos NZB , Comunicação Parácrina , Adeno-Hipófise/metabolismo , Adeno-Hipófise , Prolactina/genética , Regiões Promotoras Genéticas/genética , Receptores de Citocinas/fisiologia , Receptores da Prolactina/metabolismo , Transcrição GênicaAssuntos
Antígenos CD/fisiologia , Glicoproteínas de Membrana/fisiologia , Hipófise/fisiologia , Transdução de Sinais , Hormônio Adrenocorticotrópico/metabolismo , Animais , Receptor gp130 de Citocina , Humanos , Pró-Opiomelanocortina/metabolismo , Receptores de Citocinas/fisiologia , Estresse Fisiológico/metabolismoRESUMO
The development of the preimplantation mammalian embryo from a fertilized egg to a blastocyst capable of implanting in the uterus is a complex process. Cell division must be carefully programmed. The embryonic genome must be activated at the appropriate stage of development, and the pattern of gene expression must be carefully coordinated for the initiation of the correct program of differentiation. Cell fates must be chosen to establish specific cell types such as the inner cell mass and the trophectoderm, which give rise to the embryo proper and the placenta, respectively. This review summarizes recent findings concerning the influence of growth factors on the development of preimplantation mammalian embryos. Maternal factors secreted into the lumen of the female reproductive tract as well as substances synthesized by the developing embryo itself help to regulate this process. Studies of embryos in culture and investigations using homologous recombination to create embryos and animals null for specific genes have enabled the identification of several growth factors that appear essential for preimplantation mammalian embryo development. Some of the factors are required maternal factors; others are embryo-derived autocrine and paracrine factors. Studies using molecular biology are beginning to identify differences in the patterns of genes expressed by naturally derived embryos and those developing in culture. The knowledge gained from studies on growth factors, media, embryonic development, and gene expression should help improve culture conditions for embryos and will provide for safer outcomes from assisted reproductive procedures in human and animal clinics.
Assuntos
Fase de Clivagem do Zigoto/fisiologia , Desenvolvimento Embrionário e Fetal/fisiologia , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Substâncias de Crescimento/fisiologia , Animais , Fase de Clivagem do Zigoto/efeitos dos fármacos , Meios de Cultura/farmacologia , Citocinas/fisiologia , Transferência Embrionária , Desenvolvimento Embrionário e Fetal/efeitos dos fármacos , Feminino , Fertilização in vitro , Previsões , Substâncias de Crescimento/classificação , Substâncias de Crescimento/farmacologia , Humanos , Mamíferos/embriologia , Mamíferos/fisiologia , Camundongos , Família Multigênica , Gravidez , Receptores de Citocinas/efeitos dos fármacos , Receptores de Citocinas/fisiologia , Receptores de Fatores de Crescimento/efeitos dos fármacos , Receptores de Fatores de Crescimento/fisiologiaRESUMO
The main communicators between the neuroendocrine and immune systems are cytokines and hormones. We studied the molecular interaction between immune activators (cytokines and T-cell receptors [TCRs]) and the glucocorticoid receptor (GR) in cells in which glucocorticoids play a key regulatory function: (1) cellular targets of TNF-induced cytotoxicity; (2) the pituitary gland; and (3) thymic cells. Cytokines (TNF-alpha and IL-1) increase glucocorticoid-induced transcriptional activity of the GR via the DNA-glucocorticoid response elements (GREs) in cells transfected with a glucocorticoid-inducible reporter plasmid. As a functional physiological correlate, priming of fibroblastic cells with a low dose of TNF significantly increases the sensitivity to glucocorticoid inhibition of TNF-induced apoptosis (without involving NF-kappa B). Priming of AtT-20 mouse corticotrophs and Cushing pituitary cells with IL-1 increases the sensitivity to glucocorticoid inhibition of CRH-induced ACTH/POMC expression. In thymocytes, activation of the T-cell receptor counteracts the glucocorticoid-induced thymic apoptosis by downregulating the glucocorticoid action on GRE-driven apoptotic genes. Thus, cytokines and immune mediators prevent their own deleterious effects not only by stimulating glucocorticoid production, but also by modifying the sensitivity of the target cells for the glucocorticoid counter-regulatory action. The functional cross-talk at the molecular level between immune signals and glucocorticoids is essential to determine the biological response to both mediators and constitutes the ultimate level of interaction between the immune and neuroendocrine mediators.
Assuntos
Neuroimunomodulação , Receptor Cross-Talk/fisiologia , Receptores de Antígenos de Linfócitos T/fisiologia , Receptores de Citocinas/fisiologia , Receptores de Glucocorticoides/fisiologia , Transdução de Sinais , Animais , Citocinas/fisiologia , Humanos , Transcrição Gênica , Ativação TranscricionalRESUMO
Recent evidence has demonstrated that cytokines and other growth factors act in the anterior pituitary gland. Using the traditional criteria employed to determine autocrine or paracrine functions our review shows that, in addition to their role as lymphocyte messengers, certain cytokines are autocrine or paracrine regulators of anterior pituitary function and growth. The cytokines known to regulate and/or be expressed in the anterior pituitary include the inflammatory cytokine family (IL-1 and its endogenous antagonist, IL-1ra; TNF-alpha, and IL-6), the Th1-cytokines (IL-2 and IFN-gamma), and other cytokines such as LIF, MIF, and TGF-beta. This review examines at the cellular, molecular, and physiological levels whether: (1) each cytokine alters some aspect of pituitary physiology; (2) receptors for the cytokine are expressed in the gland; and (3) the cytokine is produced in the anterior pituitary. Should physiological stimuli regulate pituitary cytokine production, this would constitute additional proof of their autocrine/paracrine role. In this context, we analyze in this review the current literature on the actions of cytokines known to regulate anterior pituitary hormone secretion, selecting the in vivo studies that support the direct action of the cytokine in the anterior pituitary. Further support for direct regulatory action is provided by in vitro studies, in explant cultures or pituitary cell lines. The cytokine receptors that have been demonstrated in the pituitary of several species are also discussed. The endogenous production of the homologous cytokines and the regulation of this expression are analyzed. The evidence indicating that cytokines also regulate the growth and proliferation of pituitary cells is reviewed. This action is particularly important since it suggests that intrinsically produced cytokines may play a role in the pathogenesis of pituitary adenomas. The complex cell to cell communication involved in the action of these factors is discussed.
Assuntos
Citocinas/fisiologia , Adeno-Hipófise/fisiopatologia , Animais , Comunicação Autócrina , Comunicação Celular , Divisão Celular/fisiologia , Células Cultivadas , Citocinas/classificação , Humanos , Comunicação Parácrina , Receptores de Citocinas/fisiologiaRESUMO
The contributions of cytokines to the development and progression of disease in a mouse model of retrovirus-induced immunodeficiency (MAIDS) are controversial. Some studies have indicated at etiologic role for type 2 cytokines, while others have emphasized the importance of type 1 cytokines. We have used mice deficient in expression of IL-4, IL-10, IL-4 and IL-10, IFN-gamma, or ICSBP-a transcriptional protein involved in IFN signaling-to examine their contributions to this disorder. Our results demonstrate that expression of type 2 cytokines is an epiphenomenon of infection and that IFN-gamma is a driving force in disease progression. In addition, exogenously administered IL-12 prevents many manifestations of disease while blocking retrovirus expression. Interruption of the IFN signaling pathways in ICSBP-/- mice blocks induction of MAIDS. Predictably, ICSBP-deficient mice exhibit impaired responses to challenge with several other viruses. This immunodeficiency is associated with impaired production of IFN-gamma and IL-12. Unexpectedly, however, the ICSBP-/- mice also develop a syndrome with many similarities to chronic myelogenous leukemia in humans. The chronic phase of this disease is followed by a fatal blast crisis characterized by clonal expansions of undifferentiated cells. ICSBP is thus an important determinant of hematopoietic growth and differentiation as well as a prominent signaling molecule for IFNs.