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Frontiers in Bioscience : a Journal and... Jan 2007Corticotropin-releasing hormone (CRH), the principal regulator of the hypothalamic-pituitary-adrenal axis, has been identified in various organ systems, including the... (Review)
Review
Corticotropin-releasing hormone (CRH), the principal regulator of the hypothalamic-pituitary-adrenal axis, has been identified in various organ systems, including the immune and the female and male reproductive systems. CRH-like immunoreactivity has been reported in peripheral inflammatory sites and in a number of reproductive organs, including the ovaries, endometrial glands, decidualized endometrial stroma, placenta, decidua, and the testes. Therefore, "immune" and "reproductive" CRH are forms of "tissue" CRH; i.e., CRH found in peripheral tissues. Immune CRH plays a direct immunomodulatory role as an autocrine/paracrine mediator of inflammation. Immune CRH participates in several experimental inflammations and, in humans, in inflamed tissues from patients with autoimmune and inflammatory diseases. One of the early effects of immune CRH is the degranulation of mast cells and the release of histamine and several inflammatory cytokines. Reproductive CRH is regulating reproductive functions with an inflammatory component, such as ovulation, luteolysis, decidualization, implantation, and early maternal tolerance. Placental CRH participates in the physiology of pregnancy and the onset of labor. Circulating placental CRH is responsible for the physiologic hypercortisolism of the latter half of pregnancy. Postpartum, this hypercortisolism is followed by a transient adrenal suppression, which may explain the blues/depression and increased autoimmune phenomena observed during this period.
Topics: Animals; Corticotropin-Releasing Hormone; Embryo Implantation; Female; Genitalia; Humans; Immune System; Inflammation; Male; Obstetric Labor, Premature; Placenta; Pregnancy; Rats
PubMed: 17127318
DOI: 10.2741/2083 -
Neuro-Signals 2013The SDF-1α/CXCR4 signaling maintains central nervous system homeostasis through the interaction with the neurotransmitter and neuropeptide systems, the neuroendocrine... (Review)
Review
The SDF-1α/CXCR4 signaling maintains central nervous system homeostasis through the interaction with the neurotransmitter and neuropeptide systems, the neuroendocrine systems. Recently, the SDF-1α/CXCR4 signaling has been reported to present nonrandom distribution in brain development and glioma progression, which exerts differential regulations on the assembly, differentiation, and function of neural precursors, neurons, glial cells, as well as glioma cells. In the present review, we highlight current knowledge about multiple molecular signaling pathways associated with the SDF-1α/CXCR4 signaling in glioma. Not only is the expression of CXCR4 a key determinant of glioma progression, but SDF-1α is essential for site-specific invasive or metastatic processes. SDF-1α is the switch of the SDF-1α/CXCR4 signaling from the endocrine loop to the autocrine and/or local paracrine loop in glioma progression and brain development. Studies of SDF-1α/CXCR4 signaling in the field of brain development may provide valuable tactics for glioma treatment.
Topics: Brain; Brain Neoplasms; Chemokine CXCL12; Disease Progression; Glioma; Humans
PubMed: 22922481
DOI: 10.1159/000339091 -
Immunological Reviews Dec 1987The studies reviewed here support a molecular basis for bidirectional communication between the immune and neuroendocrine systems. The main findings can be summarized as... (Review)
Review
The studies reviewed here support a molecular basis for bidirectional communication between the immune and neuroendocrine systems. The main findings can be summarized as follows: First, cells of the immune system can synthesize biologically active neuroendocrine peptide hormones. Second, immune cells also possess receptors for many of these peptides. Third, these same neuroendocrine hormones can influence immune function; and fourth, lymphokines can influence neuroendocrine tissues. Although recent studies have begun to unravel the biochemistry of bidirectional communication between the immune and neuroendocrine systems, there are still missing parts in this puzzle. Among the important questions that must be resolved are the identification of factors that trigger the synthesis of neuroendocrine hormones by immune cells. Are these events operating similar to or in balance with pituitary cells? Drugs that interfere with either pathway may be useful. Second, it will be of value to understand the factors controlling neuroendocrine hormone receptor expression on immune cells. A better understanding of the spectrum of positive and negative regulatory events for both systems may determine the ultimate behavior of immune and neuroendocrine cells. In addition, since leukocytes can produce hormones and also have receptors for the same hormones (e.g., ACTH and GH), it is possible that these immunocytes may also influence their own function in an autocrine-like fashion. We have postulated that the immune system can serve as a sensory organ for external stimuli that cannot be detected by the nervous system (Blalock 1984). Thus, the immune system recognizes stimuli such as bacteria, viruses or tumors, whereas the nervous system detects classical sensory stimuli. The contribution of extrapituitary sites of hormone production and function may provide new clues to define psychological and/or pathological states in the pathophysiology of infectious diseases and tumors.
Topics: Animals; Hormones; Humans; Immune System; Neurosecretory Systems; Receptors, Cell Surface
PubMed: 2831139
DOI: 10.1111/j.1600-065x.1987.tb00528.x -
Reproductive Medicine and Biology Jan 2018Gonadotropins induce follicular development that leads to ovulation and luteinization. In women, the level of gonadotropins, along with the expression of their... (Review)
Review
BACKGROUND
Gonadotropins induce follicular development that leads to ovulation and luteinization. In women, the level of gonadotropins, along with the expression of their receptors, changes dynamically throughout the menstrual cycle. This study aimed to clarify the mechanisms underlying these phenomena.
METHODS
The literature was reviewed, including that published by the authors.
MAIN FINDINGS RESULTS
Follicle-stimulating hormone receptor expression in the granulosa cells was induced by androgens that were derived from growth differentiation factor-9-stimulated theca cells. In the theca cells, luteinizing hormone receptor (LHR) expression was noted from their appearance. In the granulosa cells, follicle-stimulating hormone (FSH) stimulation was essential for LHR expression. However, FSH alone was not sufficient to respond to the luteinizing hormone (LH) surge for oocyte maturation, ovulation, and subsequent luteinization. To achieve these stages, various local factors that were derived from the granulosa and theca cells in response to FSH and LH stimulation had to work synergistically in an autocrine/paracrine manner to strongly induce LHR expression. Following the LH surge, the LHR expression decreased markedly; miRNAs were involved in this transient LHR downregulation. Following ovulation, LHR expression drastically increased again toward luteinization.
CONCLUSION
The expression of gonadotropin receptors is controlled by sophisticated and complicated systems; a breakdown of this system could lead to ovulation disorders.
PubMed: 29371816
DOI: 10.1002/rmb2.12075 -
Endocrine Dec 2010Pituitary somatotrophs secrete growth hormone (GH) into the bloodstream, to act as a hormone at receptor sites in most, if not all, tissues. These endocrine actions of... (Review)
Review
Pituitary somatotrophs secrete growth hormone (GH) into the bloodstream, to act as a hormone at receptor sites in most, if not all, tissues. These endocrine actions of circulating GH are abolished after pituitary ablation or hypophysectomy, indicating its pituitary source. GH gene expression is, however, not confined to the pituitary gland, as it occurs in neural, immune, reproductive, alimentary, and respiratory tissues and in the integumentary, muscular, skeletal, and cardiovascular systems, in which GH may act locally rather than as an endocrine. These actions are likely to be involved in the proliferation and differentiation of cells and tissues prior to the ontogeny of the pituitary gland. They are also likely to complement the endocrine actions of GH and are likely to maintain them after pituitary senescence and the somatopause. Autocrine or paracrine actions of GH are, however, sometimes mediated through different signaling mechanisms to those mediating its endocrine actions and these may promote oncogenesis. Extrapituitary GH may thus be of physiological and pathophysiological significance.
Topics: Animals; Bone and Bones; Cardiovascular System; Gastrointestinal Tract; Genitalia; Human Growth Hormone; Humans; Immune System; Muscles; Neoplasms; Nervous System; Pituitary Gland; Respiratory System; Tissue Distribution
PubMed: 20972718
DOI: 10.1007/s12020-010-9403-8 -
The Chinese Journal of Dental Research 2013Primary saliva is formed by salivary epithelial endpieces through two pathways, the transcellular and the paracellular pathways. While the mechanisms of ion transport... (Review)
Review
Primary saliva is formed by salivary epithelial endpieces through two pathways, the transcellular and the paracellular pathways. While the mechanisms of ion transport through the transcellular pathway have been well studied, our understanding of fluid and electrolyte transport through the paracellular pathway remains rudimentary. Increasing evidence indicates that the tight junction (TJ) proteins form and regulate the paracellular pathway, although other intercellular junctions are probably involved. The structure of the TJ is complex and has not been well characterised. A functioning TJ is formed by multiple proteins, including membrane, cytoplasmic scaffolding, and signalling proteins. Paracellular fluid and electrolyte flow is mediated by high-capacity, charge- and size-restrictive small pores with a radius of 4 to 6 Å, whereas macromolecules pass through low-capacity, nonrestrictive large pores. Although the characteristics of these pores need to be further delineated, it is clear that they are under the regulation of the autonomic nervous system, endocrine, paracrine and autocrine systems, and various pathological factors. To date, the majority of the evidence for paracellular fluid and ion transport is accumulated from the studies using various epithelia other than salivary glands. Further investigations to explore the structure, function, and regulation of the paracellular pathway in salivary epithelia are needed to better understand the mechanism of saliva secretion.
Topics: Animals; Extracellular Fluid; Humans; Ion Transport; Saliva; Salivary Glands; Tight Junctions; Transcytosis
PubMed: 23878825
DOI: No ID Found -
Outside the box signaling: secreted factors modulate GnRH receptor-mediated gonadotropin regulation.Molecular and Cellular Endocrinology Mar 2014Control of gene expression following activation of membrane receptors results from the regulation of intracellular signaling pathways and transcription factors.... (Review)
Review
Control of gene expression following activation of membrane receptors results from the regulation of intracellular signaling pathways and transcription factors. Accordingly, research to elucidate the regulatory control circuits and cellular data processing mechanisms focuses on intracellular mechanisms. While autocrine and paracrine signaling are acknowledged in endocrinology, secreted factors are not typically recognized as fundamental components of the pathways connecting cell surface receptors to gene control in the nucleus. Studies of the gonadotrope suggest that extracellular regulatory loops may play a central role in the regulation of gonadotropin gene expression by gonadotropin-releasing hormone (GnRH) receptor activation. We review emerging evidence for this phenomenon, which we refer to as exosignaling, in gonadotropin gene control and in other receptor-mediated signaling systems. We propose that basic signaling circuit modules controlling gene expression can be seamlessly distributed across intracellular and exosignaling components that together orchestrate the precise physiological control of gene expression.
Topics: Animals; Autocrine Communication; Gene Expression Regulation; Gonadotrophs; Humans; Paracrine Communication; Receptors, LHRH; Signal Transduction
PubMed: 23994024
DOI: 10.1016/j.mce.2013.08.015 -
Medical Science Monitor : International... Sep 2008Ethanol has had a long and deep association with the historical development of world culture. Ostensibly, its consumption has both short and long term positive and...
Ethanol has had a long and deep association with the historical development of world culture. Ostensibly, its consumption has both short and long term positive and negative effects, based on moderate or excessive intake, respectively. The predominant thrust of empirical research, however, into the multiple biological effects of ethanol has led to its negative designation as a major addictive substance. Multiple lines of research have elucidated functional interactions of ethanol in opioid modulation of dopaminergic transmission in CNS reward systems. In parallel, recent work has demonstrated that animal cells have the ability to effect de novo synthesis of chemically authentic morphine from dopamine (DA) and DA-related aromatic precursor molecules. Interestingly, we have observed that sub-threshold concentrations of ethanol alter cellular distributions of endogenously expressed morphine. Reciprocal autocrine/paracrine modulatory effects of very low concentrations of morphine in concert with ethanol also suggest the potential for endogenous expression and action of homeopathic concentrations of ethanol within discrete cellular microdomains. Perturbation of this subtle regulatory relationship by exogenous intake of ethanol may shed light on the biochemical and molecular bases of reward and addictive states.
Topics: Alcohol Drinking; Analgesics, Opioid; Animals; Central Nervous System Depressants; Dopamine; Ethanol; Homeopathy; Humans; Morphine; Narcotics; Reward
PubMed: 18758432
DOI: No ID Found -
ACS Chemical Neuroscience Jan 2013Since its identification, 75 years ago, the monoamine serotonin (5-HT) has attracted considerable attention toward its role as a neurotransmitter in the central nervous... (Review)
Review
Since its identification, 75 years ago, the monoamine serotonin (5-HT) has attracted considerable attention toward its role as a neurotransmitter in the central nervous system. Yet, increasing evidence, from a growing number of research groups, substantiates the fact that 5-HT regulates important nonneuronal functions. Peripheral 5-HT, synthesized by the enzyme tryptophan hydroxyase (Tph) in intestinal cells, was assumed to be distributed throughout the entire body by blood platelets and to behave as a pleiotropic hormone. A decade ago, generation of a mouse model devoid of peripheral 5-HT lead to the discovery of a second isoform of the enzyme Tph and also suggested that 5-HT might act as a local regulator in various organs. The objective of this review is to highlight the newly discovered functions played by the monoamine using the Tph1 KO murine model and to outline current findings that led to the discovery of complete serotonergic systems in unexpected organs. Within an organ, both the presence of local Tph enzymatic activity and serotonergic components are of particular importance as they support the view that 5-HT meets the criteria to be qualified as a monoamine with a paracrine/autocrine function.
Topics: Animals; Autocrine Communication; Bone Remodeling; Diabetes Mellitus; Embryo, Mammalian; Erythropoiesis; Female; Homeostasis; Insulin-Secreting Cells; Intestinal Mucosa; Liver Regeneration; Mammary Glands, Animal; Mice; Mice, Knockout; Paracrine Communication; Serotonin; Tryptophan Hydroxylase
PubMed: 23336045
DOI: 10.1021/cn300154j -
Blood Oct 1994Erythropoietin (Epo) autocrine stimulation has been implicated in erythroblastic leukemia. To examine whether this stimulation could occur intracellularly, we developed...
Erythropoietin (Epo) autocrine stimulation has been implicated in erythroblastic leukemia. To examine whether this stimulation could occur intracellularly, we developed Epo autocrine models of stimulation in the human pluripotent UT-7 cell line. Retroviral expression of Epo totally abolished the growth factor requirement of UT-7 cells. Autonomous proliferation was not cell density-dependent and occurred at a unicellular level, showing a genuine autocrine mode of stimulation. Total blockage of Epo secretion induced by the endoplasmic reticulum-retention amino acids Lys-Asp-Glu-Leu (KDEL) signals in 11 lines prevented autonomous proliferation, whereas a leaky retention system, observed in 3 other lines, resulted in limited autocrine stimulation without true long-term autonomous proliferation. Production of Epo, in contrast to KDEL-modified Epo, induced reductions in Epo binding, Epo receptor (EpoR) mRNA, and phosphorylation levels similar to those induced by the addition of exogenous Epo to the parental cell line. In addition, autonomous growth and survival were inhibited by the addition of Epo-neutralizing antibodies, affording evidence that autocrine stimulation through EpoR activation takes place on the cell surface. Finally, phenotypic analysis of the virus-infected clones indicated that Epo production did not change the differentiative capacities of UT-7 cells. All these data show that Epo autocrine stimulation is dependent on Epo secretion and takes place on the cell surface. From all analyzed parameters, the effects of Epo autocrine stimulation and those of exogenously added Epo appear to be identical.
Topics: Antibodies; Base Sequence; Cell Division; Cell Line; Endoplasmic Reticulum; Erythropoietin; Gene Expression; Gene Transfer Techniques; Humans; Immunophenotyping; Molecular Sequence Data; Nucleic Acid Hybridization; Oligopeptides; Phosphorylation; Protein Sorting Signals; RNA, Messenger; Receptors, Erythropoietin; Retroviridae
PubMed: 7919379
DOI: No ID Found