Gender, Neuroendocrine‐Immune Interactions and Neuron‐Glial Plasticity: Role of Luteinizing Hormone‐Releasing Hormone (LHRH)

Abstract: Signals generated by the hypothalamic‐pitutary‐gonadal (HPG) axis powerfully modulate immune system function. This article summarizes some aspects of the impact of gender in neuroendocrine immunomodulation. Emphasis is given to the astroglial cell compartment, defined as a key actor in neuroendocrine immune communications. In the brain, the principal hormones of the HPG axis directly interact with astroglial cells. Thus, Luteinizing hormone releasing hormone, LHRH, Influences hypothalamic astrocyte development and growth, and hypothalamic astrocytes direct LHRH Neuron differentiation. Hormonally induced changes in neuron‐glial plasticity may Dictate major changes in CNS Output, and thus Actively participate in sex dimorphic immune Responses. THE Impact of gender in Neuroimmunomodulation is further underlined by The sex dimorphism in the expression of genes Encoding for neuroendocrine hormones and their Receptors within the thymus, and by the potent Modulation exerted by circulating sex steroids During development and immunization. the central Role of glucocorticoids in the interactive communication between neuroendocrine and immune systems, And the impact of gender on hypothalamic‐pituitary‐adrenocortical (HPA) axis modulation is Underscored in transgenic mice expressing a glucocorticoid receptor antisense RNA.

[1]  A. Beaudet,et al.  Basic fibroblast growth factor (bFGF) acts on both neurons and glia to mediate the neurotrophic effects of astrocytes on LHRH neurons in culture , 2000, Synapse.

[2]  L. Clement,et al.  Gonadotropin-releasing hormone increases CD4 T-lymphocyte numbers in an animal model of immunodeficiency. , 1999, The Journal of allergy and clinical immunology.

[3]  M. C. Morale,et al.  Partial blockade of T-cell differentiation during ontogeny and marked alterations of the thymic microenvironment in transgenic mice with impaired glucocorticoid receptor function , 1999, Journal of Neuroimmunology.

[4]  A. Giovambattista,et al.  Gender-dependent characteristics of the hypothalamo-corticotrope axis function in glucocorticoid-replete and glucocorticoid-depleted rats , 1998, Journal of endocrinological investigation.

[5]  S. Finklestein,et al.  Estradiol Protects against Ischemic Injury , 1998, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[6]  F. Holsboer,et al.  Reduced Activity of Hypothalamic Corticotropin-Releasing Hormone Neurons in Transgenic Mice with Impaired Glucocorticoid Receptor Function , 1998, The Journal of Neuroscience.

[7]  C. Tirolo,et al.  Luteinizing Hormone‐Releasing Hormone Is a Primary Signaling Molecule in the Neuroimmune Network , 1998, Annals of the New York Academy of Sciences.

[8]  G. Adamus,et al.  Gonadal hormones influence the immune response to PLP 139–151 and the clinical course of relapsing experimental autoimmmune encephalomyelitis , 1998, Journal of Neuroimmunology.

[9]  B. McEwen.  Protective and damaging effects of stress mediators. , 1998, The New England journal of medicine.

[10]  C. Tirolo,et al.  Developmental consequences of hypothalamic-pituitary-adrenocortical system disruption: Impact on thymus gland maturation and the susceptibility to develop neuroimmune diseases , 1997 .

[11]  B. Waddell,et al.  Circadian variation in basal plasma corticosterone and adrenocorticotropin in the rat: sexual dimorphism and changes across the estrous cycle. , 1997, Endocrinology.

[12]  F. Holsboer,et al.  Hypothalamic-Pituitary-Adrenocortical Axis Changes in a Transgenic Mouse with Impaired Glucocorticoid Receptor Function. , 1997, Endocrinology.

[13]  L. Schneider,et al.  Can Estrogens Prevent Neurodegeneration? , 1997, Drugs & aging.

[14]  R. Voskuhl,et al.  Testosterone therapy ameliorates experimental autoimmune encephalomyelitis and induces a T helper 2 bias in the autoantigen-specific T lymphocyte response. , 1997, Journal of immunology.

[15]  F. Holsboer,et al.  Neuroprotection against oxidative stress by estrogens: structure-activity relationship. , 1997, Molecular pharmacology.

[16]  B. Marchetti,et al.  Cross-talk signals in the CNS: role of neurotrophic and hormonal factors, adhesion molecules and intercellular signaling agents in luteinizing hormone-releasing hormone (LHRH)-astroglial interactive network. , 1997, Frontiers in bioscience : a journal and virtual library.

[17]  O. Almeida,et al.  Gonadal Steroids Exert Facilitating and “Buffering” Effects on Glucocorticoid-Mediated Transcriptional Regulation of Corticotropin-Releasing Hormone and Corticosteroid Receptor Genes in Rat Brain , 1996, The Journal of Neuroscience.

[18]  R. Sapolsky,et al.  Stress, Glucocorticoids, and Damage to the Nervous System: The Current State of Confusion. , 1996, Stress.

[19]  A. MacKenzie-Graham,et al.  Gender differences in autoimmune demyelination in the mouse: Implications for multiple sclerosis , 1996, Annals of neurology.

[20]  F. Holsboer,et al.  Antidepressants and hypothalamic-pituitary-adrenocortical regulation. , 1996, Endocrine reviews.

[21]  M. C. Morale,et al.  Growth Factors Released from Astroglial Cells in Primary Culture Participate in the Cross Talk between Luteinizing Hormone–Releasing Hormone (LHRH) Neurons and Astrocytes , 1996, Annals of the New York Academy of Sciences.

[22]  M. C. Morale,et al.  Luteinizing Hormone‐Releasing Hormone (LHRH) Receptors in the Neuroendocrine‐Immune Network , 1996 .

[23]  M. C. Morale,et al.  Disruption of hypothalamic-pituitary-adrenocortical system in transgenic mice expressing type II glucocorticoid receptor antisense ribonucleic acid permanently impairs T cell function: effects on T cell trafficking and T cell responsiveness during postnatal development. , 1995, Endocrinology.

[24]  G. Chrousos,et al.  The hypothalamic-pituitary-adrenal axis and immune-mediated inflammation. , 1995, The New England journal of medicine.

[25]  B. McEwen,et al.  Stress and cognitive function , 1995, Current Opinion in Neurobiology.

[26]  C. Finch,et al.  Increases of glial fibrillary acidic protein in the aging female mouse brain , 1995, Neurobiology of Aging.

[27]  C. Finch,et al.  Food restriction delays the age-related increase in GFAP mRNA in rat hypothalamus , 1995, Neurobiology of Aging.

[28]  F. Holsboer,et al.  Do antidepressants stabilize mood through actions on the hypothalamic-pituitary-adrenocortical system? , 1995, Trends in Neurosciences.

[29]  P. Collado,et al.  Hypothalamic distribution of astrocytes is gender-related in Mongolian gerbils , 1995, Neuroscience Letters.

[30]  C. Finch,et al.  Glial fibrillary acidic protein mRNA increases at proestrus in the arcuate nucleus of mice , 1995, Neuroscience Letters.

[31]  I. Torres-Aleman,et al.  Gonadal steroids as promoters of neuro-glial plasticity , 1994, Psychoneuroendocrinology.

[32]  J. McQueen,et al.  The Development of Astrocytes Immunoreactive for Glial Fibrillary Acidic Protein in the Mediobasal Hypothalamus of Hypogonadal Mice , 1994, Molecular and Cellular Neuroscience.

[33]  J. Blalock.  Shared Ligands and Receptors As a Molecular Mechanism for Communication between the Immune and Neuroendocrine Systems , 1994, Annals of the New York Academy of Sciences.

[34]  W. Pierpaoli.  The Pineal Gland as Ontogenetic Scanner of Reproduction, Immunity, and Aging The Aging Clock , 1994, Annals of the New York Academy of Sciences.

[35]  M. C. Morale,et al.  Characterization, expression, and hormonal control of a thymic beta 2-adrenergic receptor. , 1994, The American journal of physiology.

[36]  A. Steinberg,et al.  Modulation of the expression of murine lupus by gonadotropin-releasing hormone analogs. , 1994, Endocrinology.

[37]  M. C. Morale,et al.  Transgenic Animals with Impaired Type II Glucocorticoid Receptor Gene Expression , 1994, Annals of the New York Academy of Sciences.

[38]  C. Rivier.  Stimulatory effect of interleukin-1 beta on the hypothalamic-pituitary-adrenal axis of the rat: influence of age, gender and circulating sex steroids. , 1994, The Journal of endocrinology.

[39]  J. C. King,et al.  Luteinizing hormone-releasing hormone terminals in the median eminence of rats undergo dramatic changes after gonadectomy, as revealed by electron microscopic image analysis. , 1994, Endocrinology.

[40]  J. G. Estrada,et al.  Is the immune system necessary for placental reproduction? A hypothesis on the mechanisms of alloimmunotherapy in recurrent spontaneous abortion. , 1994, Medical hypotheses.

[41]  Á. Párducz,et al.  Gonadal hormone regulation of glial fibrillary acidic protein immunoreactivity and glial ultrastructure in the rat neuroendocrine hypothalamus , 1994, Glia.

[42]  S. Kalra,et al.  Evidence that nitric oxide may mediate the ovarian steroid-induced luteinizing hormone surge: involvement of excitatory amino acids. , 1993, Endocrinology.

[43]  M. Moretto,et al.  Nitric oxide regulates luteinizing hormone-releasing hormone secretion. , 1993, Endocrinology.

[44]  G. Kroemer,et al.  Immunoendocrine communication via the hypothalamo-pituitary-adrenal axis in autoimmune diseases. , 1993, Endocrine reviews.

[45]  S. Kalra.  Mandatory neuropeptide-steroid signaling for the preovulatory luteinizing hormone-releasing hormone discharge. , 1993, Endocrine reviews.

[46]  D. Reis,et al.  Synthesis of nitric oxide in CNS glial cells , 1993, Trends in Neurosciences.

[47]  M. Kelley,et al.  Immunoactivation enhances the concentration of luteinizing hormone-releasing hormone peptide and its gene expression in human peripheral T-lymphocytes. , 1993, Endocrinology.

[48]  K. Catt,et al.  Expression of gonadotropin-releasing hormone receptors and autocrine regulation of neuropeptide release in immortalized hypothalamic neurons. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[49]  C. Léránth,et al.  Estrogen induces synaptic plasticity in adult primate neurons. , 1993, Neuroendocrinology.

[50]  U. Kaiser,et al.  Isolation and characterization of cDNAs encoding the rat pituitary gonadotropin-releasing hormone receptor. , 1992, Biochemical and biophysical research communications.

[51]  R. Weiner,et al.  Dopaminergic regulation of the GT1 gonadotropin-releasing hormone (GnRH) neuronal cell lines: stimulation of GnRH release via D1-receptors positively coupled to adenylate cyclase. , 1992, Endocrinology.

[52]  E. Spinedi,et al.  Effects of gonadectomy and sex hormone therapy on the endotoxin-stimulated hypothalamo-pituitary-adrenal axis: evidence for a neuroendocrine-immunological sexual dimorphism. , 1992, Endocrinology.

[53]  M. Costa,et al.  Transforming growth factor-α gene expression in the hypothalamus is developmentally regulated and linked to sexual maturation , 1992, Neuron.

[54]  Robert M. Sapolsky,et al.  Stress, the Aging Brain, and the Mechanisms of Neuron Death , 1992 .

[55]  M. C. Morale,et al.  The immune response evokes up- and down-modulation of beta 2-adrenergic receptor messenger RNA concentration in the male rat thymus. , 1992, Molecular endocrinology.

[56]  E. Baulieu,et al.  Demonstration of steroid hormone receptors and steroid action in primary cultures of rat glial cells , 1992, The Journal of Steroid Biochemistry and Molecular Biology.

[57]  N. Barden,et al.  Impaired type II glucocorticoid-receptor function in mice bearing antisense RNA transgene , 1992, Nature.

[58]  A. Silverman,et al.  Relationship of glia to GnRH axonal outgrowth from third ventricular grafts in hpg hosts , 1991, Experimental Neurology.

[59]  N. Barden,et al.  Hormonal regulation of type II glucocorticoid receptor messenger ribonucleic acid in rat brain. , 1991, Endocrinology.

[60]  C. Sumners,et al.  Expression of mineralocorticoid type I and glucocorticoid type II receptors in astrocyte glia as a function of time in culture. , 1991, Brain research. Developmental brain research.

[61]  M. C. Morale,et al.  Aging of the Reproductive‐Neuroimmune Axis , 1991, Annals of the New York Academy of Sciences.

[62]  M. C. Morale,et al.  Luteinizing hormone-releasing hormone signaling at the lymphocyte involves stimulation of interleukin-2 receptor expression. , 1991, Endocrinology.

[63]  J. Tentler,et al.  Presence of luteinizing hormone-releasing hormone (LHRH) mRNA in rat spleen lymphocytes. , 1991, Endocrinology.

[64]  E. Baulieu,et al.  Estrogen-inducible progesterone receptor in primary cultures of rat glial cells. , 1991, Experimental cell research.

[65]  M. C. Morale,et al.  Blockade of central and peripheral luteinizing hormone-releasing hormone (LHRH) receptors in neonatal rats with a potent LHRH-antagonist inhibits the morphofunctional development of the thymus and maturation of the cell-mediated and humoral immune responses. , 1991, Endocrinology.

[66]  S. Ojeda,et al.  Involvement of transforming growth factor alpha in the release of luteinizing hormone-releasing hormone from the developing female hypothalamus. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[67]  S. Sealfon,et al.  Hormonal regulation of gonadotropin-releasing hormone receptors and messenger RNA activity in ovine pituitary culture. , 1990, Molecular endocrinology.

[68]  M. C. Morale,et al.  The thymus gland as a major target for the central nervous system and the neuroendocrine system: Neuroendocrine modulation of thymic β2-Adrenergic receptor distribution as revealed by in vitro autoradiography , 1990, Molecular and Cellular Neuroscience.

[69]  J. Windle,et al.  Immortalization of hypothalamic GnRH by genetically targeted tumorigenesis , 1990, Neuron.

[70]  M. C. Morale,et al.  Cross‐Talk Communication in the Neuroendocrine‐Reproductive‐Immune Axis. , 1990, Annals of the New York Academy of Sciences.

[71]  L. Garcia-Segura,et al.  Synaptic remodeling in the rat arcuate nucleus during the estrous cycle , 1989, Neuroscience.

[72]  W. Sakr,et al.  Effect of GnRH agonists on the thymus in female rats. , 1989, Acta endocrinologica.

[73]  E. Baulieu,et al.  Neurosteroids: biosynthesis of pregnenolone and progesterone in primary cultures of rat glial cells. , 1989, Endocrinology.

[74]  M. C. Morale,et al.  Luteinizing hormone-releasing hormone (LHRH) agonist restoration of age-associated decline of thymus weight, thymic LHRH receptors, and thymocyte proliferative capacity. , 1989, Endocrinology.

[75]  M. C. Morale,et al.  Luteinizing hormone-releasing hormone-binding sites in the rat thymus: characteristics and biological function. , 1989, Endocrinology.

[76]  I. Torres-Aleman,et al.  Astrocytic shape and glial fibrillary acidic protein immunoreactivity are modified by estradiol in primary rat hypothalamic cultures. , 1989, Brain research. Developmental brain research.

[77]  K. Fuxe,et al.  Localization of glucocorticoid receptor mRNA in the male rat brain by in situ hybridization. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[78]  K. Pfenninger,et al.  Estrogen and insulin synergism in neurite growth enhancement in vitro: mediation of steroid effects by interactions with growth factors? , 1988, Brain research.

[79]  N. Barden,et al.  Glucocorticoid receptor gene expression in rat pituitary gland intermediate lobe following ovariectomy , 1988, Molecular and Cellular Endocrinology.

[80]  B. Robaire,et al.  Modulation by neonatal thymectomy of the reproductive axis in male and female rats during development. , 1988, Biology of reproduction.

[81]  N. Barden,et al.  Estrogen-induced decrease of glucocorticoid receptor messenger ribonucleic acid concentration in rat anterior pituitary gland. , 1987, Molecular endocrinology.

[82]  M. Wheeler,et al.  Regeneration of the thymus in old male rats treated with a stable analogue of LHRH. , 1987, The Journal of endocrinology.

[83]  M. Valença,et al.  Transmembrane signals mediating neural peptide secretion: role of protein kinase C activators and arachidonic acid metabolites in luteinizing hormone-releasing hormone secretion. , 1986, Endocrinology.

[84]  S. Ojeda,et al.  Activation of two different but complementary biochemical pathways stimulates release of hypothalamic luteinizing hormone-releasing hormone. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[85]  E. R. Kloet,et al.  Two receptor systems for corticosterone in rat brain: microdistribution and differential occupation. , 1985, Endocrinology.

[86]  B. B. Turner,et al.  Sexual dimorphism of glucocorticoid binding in rat brain , 1985, Brain Research.

[87]  L. Birnbaumer,et al.  Evidence for a physiological role of gonadotropin-releasing hormone (GnRH) or GnRH-like material in the ovary. , 1985, Endocrinology.

[88]  L. S. Perlmutter,et al.  Dynamic neuronal-glial interactions in hypothalamus and pituitary: Implications for control of hormone synthesis and release , 1984, Peptides.

[89]  C. Grossman.  Regulation of the immune system by sex steroids. , 1984, Endocrine reviews.

[90]  B. Marchetti,et al.  Prolactin inhibits pituitary luteinizing hormone-releasing hormone receptors in the rat. , 1982, Endocrinology.

[91]  B. Marchetti,et al.  Modulation of pituitary luteinizing hormone releasing hormone receptors by sex steroids and luteinizing hormone releasing hormone in the rat. , 1982, Biology of reproduction.

[92]  W. LeMaire,et al.  Gonadotropin releasing hormone agonists stimulate meiotic maturation of follicle-enclosed rat oocytes in vitro , 1980, Nature.

[93]  W. Pierpaoli,et al.  Role of the thymus in programming of neuroendocrine functions. , 1975, Clinical and experimental immunology.

[94]  H. Besedovsky,et al.  Thymus involvement in female sexual maturation , 1974, Nature.

[95]  U. Westphal,et al.  Corticosteroid-binding globulin in the rat: studies on the sex difference. , 1965, Endocrinology.

[96]  R. Liebelt,et al.  Sex difference in resting pituitary-adrenal function in the rat. , 1963, The American journal of physiology.

[97]  W. Barker,et al.  Medulloblastoma cerebelli; diagnosis, treatment and survivals, with a report of 56 cases. , 1948, The New England journal of medicine.

[98]  C. Tirolo,et al.  Neurochemical, immunological and pharmacological assessments in a transgenic mouse model of the endocrine changes in depression , 1997, Aging.

[99]  F. Holsboer,et al.  Hypothalamic-pituitary-adrenocortical axis changes in a transgenic mouse with impaired glucocorticoid receptor function. , 1997, Endocrinology.

[100]  B. Marchetti.  The LHRH-astroglial network of signals as a model to study neuroimmune interactions: assessment of messenger systems and transduction mechanisms at cellular and molecular levels. , 1996, Neuroimmunomodulation.

[101]  M. C. Morale,et al.  Luteinizing hormone-releasing hormone (LHRH) receptors in the neuroendocrine-immune network. Biochemical bases and implications for reproductive physiopathology. , 1996, Annals of the New York Academy of Sciences.

[102]  M. Kelley,et al.  Coordinate gene expression of luteinizing hormone-releasing hormone (LHRH) and the LHRH-receptor after prolactin stimulation in the rat Nb2 T-cell line: implications for a role in immunomodulation and cell cycle gene expression. , 1995, Molecular endocrinology.

[103]  E. Spinedi,et al.  Sex and strain variability in the rat hypothalamo-pituitary-adrenal (HPA) axis function , 1995 .

[104]  F. Holsboer,et al.  Dexamethasone nonsuppression in transgenic mice expressing antisense RNA to the glucocorticoid receptor. , 1994, Journal of psychiatric research.

[105]  W. L. Dees,et al.  Induction by cytokines of the pattern of pituitary hormone secretion in infection. , 1994, Neuroimmunomodulation.

[106]  M. C. Morale,et al.  Modulation of glucocorticoid receptor gene expression in the thymus by the sex steroid hormone milieu and correlation with sexual dimorphism of immune response , 1994 .

[107]  R. Cleveland,et al.  Sequential changes in functional lymphocyte subpopulations during long term administration of GnRH agonist in postpubertal female mice , 1993 .

[108]  I. Sargent.  Maternal and fetal immune responses during pregnancy. , 1993, Experimental and clinical immunogenetics.

[109]  S. Mccann,et al.  Endocrine Aspects of Neuroimmunomodulation: Methods and Overview , 1993 .

[110]  M. C. Langub,et al.  Estrogen receptor-immunoreactive glia, endothelia, and ependyma in guinea pig preoptic area and median eminence: electron microscopy. , 1992, Endocrinology.

[111]  S. Ojeda,et al.  Neurotrophic factors and female sexual development. , 1992, Frontiers in neuroendocrinology.

[112]  J. de Vellis,et al.  Early response gene induction in astrocytes as a mechanism for encoding and integrating neuronal signals. , 1992, Progress in brain research.

[113]  D. Harrison,et al.  Central nervous system astroglial cells release nitrogen oxide(s) with vasorelaxant properties , 1991 .

[114]  T. Strom,et al.  Evidence that glucocorticosteroids block expression of the human interleukin-6 gene by accessory cells. , 1990, Transplantation.

[115]  B. Marchetti,et al.  Beta-adrenergic receptors in the rat mammary gland during pregnancy and lactation: characterization, distribution, and coupling to adenylate cyclase. , 1990, Endocrinology.

[116]  M. C. Morale,et al.  A physiological role for the neuropeptide luteinizing hormone-releasing hormone (LHRH) during the maturation of thymus gland function. , 1990, The International journal of neuroscience.

[117]  J. Roberts,et al.  Immortalization of hypothalamic GnRH neurons by genetically targeted tumorigenesis. , 1990, Neuron.

[118]  N. H. Spector,et al.  Neuroimmunomodulation: Interventions in aging and cancer , 1988 .

[119]  B. Marchetti,et al.  Modulation of opioid influence on pituitary luteinizing hormone-releasing hormone (LHRH) receptors by progesterone and estrogen in the female rat , 1985 .

[120]  E. Horstmann.  [The fiber glia of selacean brain]. , 1954, Zeitschrift fur Zellforschung und mikroskopische Anatomie.