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PubMed1999

Cellular distribution of endothelin-converting enzyme-1 in human tissues.

Endothelin-converting enzyme-1 (ECE-1) is the key enzyme of endothelin biosynthesis, catalyzing the final processing step. As shown by the targeted disruption of the ECE-1 gene, mature endothelins must be produced at specific sites for normal embryonic development. Therefore, it is important to know the exact pattern of ECE-1 gene expression. In this study we investigated the cellular distribution of ECE-1 in a variety of human tissues by in situ hybridization and immunohistochemistry. Widespread expression of the ECE-1 gene was noted, with a similar distribution pattern for mRNA and protein in normal human tissues, suggesting a major biological role for ECE-1. ECE-1 levels were particularly high in the cardiovascular, reproductive, and endocrine systems. There was strong and consistent labeling for ECE-1 in the vascular endothelial cells of all organs examined and in various nonvascular cells, especially some glandular cells. A large amount of ECE-1 protein and mRNA was detected in the Leydig cells of the testis and in the granulosa and theca cells of the ovary. In the adrenal gland, ECE-1 was detected in the cortex and medulla, with the strongest labeling in the zona glomerulosa. Therefore, ECE-1 may be involved in other systems, such as the regulation of hormone secretion, rather than exclusively generating ET-1 from its precursor. These results point out the potential side effects of ECE-1 inhibitors that are currently under development for treatment of cardiovascular diseases. (J Histochem Cytochem 47:447-461, 1999)

Adolescent↗

PubMed1998

Vascular smooth muscle, endothelial regulation and effects of aspirin in hypertension.

Dysfunction of vascular smooth muscle (VSM) is at the center of occlusive disorders of the cardiovascular system such as hypertension, atherosclerosis, coronary artery disease and hypoxia. In addition to circulating biogenic amines and various neurotransmitters originating from the central nervous system and endocrine system, various autocoids of arachidonic acid metabolism in the blood as well as in the endothelium play an important regulatory role in the maintenance of the tone and the contractile function of VSM. A monolayer of endothelial cells lining the heart and large blood vessels is responsible for producing and releasing both endocrine and paracrine substances such as endothelins, nitric oxide, prostaglandins and prostacyclins. Aspirin, (acetylsalicylic acid/ASA) an ancient remedy against fever and pain, is emerging as an effective drug not only against occlusive disorders but also against various cancers and the AIDs virus. During pregnancy induced hypertension (PIH) and in occlusive disorders, aspirin provides relief through inhibition of cyclooxygenase, an enzyme required for the metabolism of arachidonic acid to produce prostaglandins and prostacyclins in platelets and in endothelial cells. Because of its unique molecular constitution, synergistic ability and solubility in the lipidic environment, various mechanisms of aspirin's actions are being currently investigated. In this review, the effect of aspirin on the regulation of VSM in the presence and absence of endothelium are discussed.

Animals↗

PubMed2002

Development of a new xenoestrogen screening system using fission yeast Schizosaccharomyces pombe.

Endocrine disrupters refer to environmental or chemical compounds, which interfere with the endocrine system of organisms. In this study, our aim was to develop a screening method to detect xenoestrogen (an endocrine disrupter that is commonly encountered in our daily life) by using fission yeast Schizosaccharomyces pombe. Although the yeast (the simplest eukaryotic cell) has no endocrine system, estrogen receptors that are created to express in the yeast cell can be activated by estrogen in a similar manner to mammalian cells. First, in order to express the human estrogen receptor (hER) in the yeast cell, we constructed a yeast expression vector that contained hER (pREP42MHN-hER). In the yeast cells that are transformed with the pREP42MHN-hER vector, estrogen receptors could recognize xenoestrogen, which allowed the determination of the presence of xenoestrogen in any given sample. Furthermore, we constructed a yeast strain that contained an estrogen responsive element (ERE) that fused with the Escherichia coli LacZ gene (pERE-LacZ) as a reporter for binding of xenoestrogen with the estrogen receptor. Since this vector system allows determination of the presence and level of xenoestrogen with simple procedures, it is expected that they can serve as an efficient assay system to detect xenoestrogen.

Artificial Gene Fusion↗

PubMed1991

[Physiological and pathological aging and electrolyte metabolism].

The extracellular and intracellular concentrations of electrolyte were maintained by various systems including kidney and endocrine system. Although concentrations of electrolyte in the extracellular fluid were maintained in normal ranges in healthy elderly subjects, the reserve ability for the maintenance of electrolyte balance decreases with physiological aging. Occurrence of abnormality in electrolyte concentrations in extracellular fluid is thought to be related to pathological aging. The frequency of subjects with abnormal circulating concentrations of electrolytes, as well as abnormal rates of severe such abnormalities increase with age. Clinical characterization and differentiation of physiological and pathological aging are not always easy. On the other hand, the kidney is the central organ for maintenance of electrolyte homeostasis. Decrease in renal ability to retain electrolytes sometimes affect the features of disorders such as hypertension and osteoporosis of elderly subjects. Intravenous infusion of physiological saline at a dose of 20 ml/kg over 2 hr evoked excessive excretion of sodium, calcium and inorganic phosphate in the urine in hypertensive elderly patients and in some patients with senile osteoporosis. These subjects showed decreased levels of plasma renin activity and increased serum levels of parathyroid hormone and 1,25-dihydroxyvitamin D. These features indicate that abnormal renal metabolization of electrolytes involving abnormality of endocrine system may be a cause of, and modulate the clinical features of, some disorders of elderly subjects.

Aged↗

PubMed1995

The commercial and agricultural applications of animal transgenesis.

The potential for commercial application of transgenic technologies in domestic animals is discussed in relation to the areas where a significant impact on agriculture might be expected. These are the endocrine system, novel biochemical pathways, structural proteins of milk and of textile fibers, and the immune system. Manipulation of the endocrine system has been investigated for some years and it is clear that very accurate control is needed over gene expression if this approach is to prove commercially useful. The area most advanced in commercial application is the production of high-value pharmaceutical proteins in the mammary glands of domestic animals. Other applications that are discussed remain to be proven in larger animals despite being demonstrated laboratory test animals. These include a functional cysteine biosynthetic pathway and a functional glyoxylate cycle transferred from bacteria to mice, and alterations to the proteins of hair that change the physical properties of the resultant fibers. Research is also actively directed toward novel approaches for providing domestic animals with resistance to insects.

Agriculture↗

PubMed1987

Increased populations of endocrine cells in Crohn's ileitis.

Hyperplasia of nerves has been described previously in Crohn's disease. To determine whether similar alteration of the enteric endocrine system occurs, endocrine cells of the ileal epithelium were quantified in typical cases of the disease. In the ileum from patients with Crohn's disease, there was an increase in the endocrine cell population, as visualised by immunostaining of chromogranin. Quantification of endocrine cell numbers showed significant increases in both macroscopically uninvolved (i.e. histologically normal) (35.0 +/- 3.8, cells per unit length of muscularis mucosae mean +/- SEM, P less than 0.05) and involved (44.5 +/- 5.5, P less than 0.01) Crohn's disease samples, compared with normal controls (23.7 +/- 3.4). Although individual types of endocrine cell showed slight increases in Crohn's samples, only the enterochromaffin cells in abnormal bowel showed a significantly greater population (normal controls 10.5 +/- 2.3; involved Crohn's 21.3 +/- 4.4, P less than 0.05).

Antigens↗

PubMed1995

Mycotoxins: risk assessment and legislation.

Mycotoxins are naturally occurring toxic secondary metabolites of fungi that may be present in food products. Several mycotoxins have been associated with and implicated in human and animal disease. Mycotoxins encompass a wide spectrum of different chemicals and they may affect many target organs and systems, notably the liver, kidney, the nervous system, the endocrine system, and the immune system. Much of our concern is about chronic effects at low levels of exposure, and several mycotoxins have been classified by the International Agency for Research in Cancer as human carcinogens or potential human carcinogens. Although these toxicants can never be completely removed from the food supply, it is possible through risk assessment to define levels that are unlikely to be of health concern. Ideally the risk assessment involves a complete toxicological assessment, an epidemiological assessment and an exposure assessment. However, in the risk management of mycotoxins it may be deemed necessary to take action before all this information is available. In this presentation recent risk management of the fumonisins will be compared with the situation for aflatoxins.

Aflatoxins↗

PubMed2004

The phenotype of gut endocrine tumours.

Endocrine tumours of gut and pancreas tract are rare entities originating from cells of the diffuse endocrine system. The endocrine phenotype is assessed by the expression of general and specific endocrine markers. General endocrine markers associate to organelles like large dense core vesicles (e.g. chromogranin A) and small synaptic-like vesicles (e.g. synaptophysin), or to the cytosol, like neuron specific enolase and protein gene product 9.5 (PGP9.5). The specific markers correspond to the hormones produced by tumour cells. Two major categories of endocrine tumours are identified as (i) well-differentiated and (ii) poorly differentiated neoplasms. Well-differentiated tumours/carcinomas (also known as carcinoids) express all general markers of endocrine differentiation and various hormones. Poorly differentiated endocrine carcinomas lack large dense core vesicles markers (chromogranin A), while widely express synaptophysin and cytosol endocrine markers. The clinical behaviour of endocrine tumours spans from benign to low-grade malignant for well-differentiated tumours/carcinomas to high grade malignant for poorly differentiated carcinomas. The Multiple Endocrine Neoplasia type 1 syndrome (MEN1) gene is involved in the genesis of a proportion of both well- and poorly differentiated sporadic tumours. p53 gene abnormality appears as restricted to poorly differentiated endocrine carcinomas.

Biomarkers, Tumor↗

PubMed2004

Neuropeptide Y (NPY).

Neuropeptides such as neuropeptide Y (NPY) have long been proposed to play a role in the pathogenesis of inflammatory diseases. NPY is a 36 amino acid neuropeptide which participates in the regulation of a large number of physiological and pathophysiological processes in the cardiorespiratory system, immune system, nervous system and endocrine system. Serum levels of NPY are increased during exacerbations of asthma, whereas the number of NPY-immunoreactive nerves in the airways remains constant in the airways of patients with inflammatory airway diseases such asthma or rhinitis. Next to a role in the regulation of glandular activity, NPY exerts a major influence on humoral and cellular immune functions. In this respect, NPY is known to modulate potent immunological effects such as immune cell distribution, T helper cell differentiation, mediator release, or natural killer cell activation. In addition to these direct effects, NPY also acts as an immunomodulator by influencing the effects of a variety of other neurotransmitters. Whereas the peptide has been focused for therapeutic options in the central nervous system, a potential use in the treatment of pulmonary inflammatory disorders has not been revealed so far due to the complex pulmonary effects of NPY. However, since selective antagonists and agonists and gene-depleted animals for the different receptors are now available, NPY may be of value for future strategies in airway nerve modulation.

Animals↗

PubMed1990

Body composition, normal electrolyte concentrations, and the maintenance of normal volume, tonicity, and acid-base metabolism.

Because the internal environment of the body is largely a fluid medium, the preservation of the volume and composition of the body fluids is absolutely vital to circulatory status and the extraordinarily complicated functions of the human body. The fluid compartments do not exist as fixed spaces with identical compositions but rather are in constant interchange with each other and have strikingly different compositions. Methods of movement of solutes and water include diffusion along electrochemical gradients, by hydrostatic pressure, osmotic forces, bulk flow, primary and secondary active transport, capillary blood flow, and oncotic pressure. Complex feedback control mechanisms exist to ensure homeostasis or equilibrium and include participation by the kidneys, lungs, gastrointestinal tract, the circulatory system, the endocrine system, and the CNS. The maintenance of extracellular volume is centered around the control of balance of the sodium salts. Multiple afferent (or sensing) and efferent (or effector) mechanisms exist to accomplish this homeostasis. The most important determinants of the osmolality or tonicity of the body fluids is the excretion or retention of water by the kidney, thirst mechanisms, and the intake of water. The serum sodium concentration is the laboratory test most often used clinically to assess tonicity. The pH of the body fluids and the major acid-base buffer systems are also carefully regulated. The lungs are responsible for the elimination of the carbon dioxide produced by cellular metabolism, and the kidneys excrete hydrogen ions and regulate the concentration of bicarbonate in the body fluids. Urinary net acid excretion, the hydrogen ions excreted as titratable acid and ammonium ions minus any bicarbonate, equals the acid added to the ECF from the diet and metabolism plus any fecal losses of alkali.

Acid-Base Equilibrium↗

PubMed1999

Amphibians as a model to study endocrine disruptors: I. Environmental pollution and estrogen receptor binding.

Many chemicals released into the environment without toxicological risks have the capacities to disrupt the function of endocrine systems. These endocrine disruptors disturb normal endocrine mechanisms and have been observed in nearly all classes of vertebrates. The aim of this research is to develop a comprehensive model to study endocrine disruption using the amphibian Xenopus laevis. The assessment of estrogenic potencies of endocrine disruptors includes several levels of investigation: (I) binding to liver estrogen receptor, (II) estrogenic activity in vitro by inducing vitellogenin synthesis in primary cultured hepatocytes, and (III) in vivo effects on sexual development caused by exposure of larvae. The present paper is focused on the first part by establishing a radioreceptorassay for [3H]17 beta-estradiol ([3H]E2) binding using liver cytosol fraction. In order to get optimum binding conditions we performed kinetic, saturation, and competitive displacement experiments. Association of [3H]E2 to estrogen receptor revealed that maximum specific binding is achieved between 18 and 48 h of incubation. Scatchard analyses of saturation experiments resulted in a homogenous saturable population of estrogen receptors having no significant differences of binding parameters between both sexes. The values of Kd (dissociation constant) in males and females were 22.4 +/- 6.0 and 15.0 +/- 2.8 nM (mean +/- S.E.M.; n = 5), respectively, while corresponding Bmax (maximum binding capacity) revealed 89 +/- 46 and 136 +/- 46 fmol [3H]E2/mg protein. The specificity of estrogen receptors as shown by competitive displacement experiments demonstrated receptors being highly specific just for estrogens, but not for other endogenous steroids having the following ranking of binding affinities: E2 > estrone > dehydroepiandrosterone > aldosterone > or = testosterone > or = corticosterone > or = progesterone. The affinity ranking of environmental chemicals compared to E2 was: E2 > tetrachlorbiphenyl > diethylphthalate > 2,2-bis-(4-hydroxyphenyl)-propan (bisphenol A) > or = 4-nonylphenol > or = 3-t-butyl-4-hydroxyanisole > or = 4-octylphenol > dichlor-diphenyl-trichlor-ethan (4,4'-DDT). Analyses of five sewage effluents for displacement of [3H]E2 binding resulted in three samples displacing more than 50% of specific binding at their original concentration. Taken together the established radioreceptorassay for [3H]E2 binding in Xenopus laevis liver cytosol is useful to screen estrogen receptor binding of pure compounds or complex mixtures of them, which is the prerequisite for causing either estrogenic or antiestrogenic effects.

Animals↗

PubMed1981

Anterior segment and retinal pigmentary abnormalities in arteriohepatic dysplasia.

Arteriohepatic dysplasia (AHD, Alagille's syndrome) is presumed to be one of the six known familial intrahepatic cholestatic syndromes, all of which present with neonatal jaundice or failure to thrive, or both. Accurate early diagnosis of the proper syndrome is important, as arteriohepatic dysplasia has a good prognosis, whereas the other syndromes usually lead to death in infancy or early adulthood. Posterior embryotoxon was found in all five of our patients and may be one of the hallmarks of this syndrome. Axenfeld's anomaly was present in three of five patients, and retinal pigmentary abnormalities were found in four of five patients. Variable abnormalities were found in the cardiovascular system, bones, central nervous system, kidneys, endocrine system, and body habitus. Inheritance may be autosomal dominant as vertical transmission was documented in one family. Liver function improves during the first five years of life so that only the ocular and skeletal signs may be present in adults.

Abnormalities, Multiple↗

PubMed2000

Stress-induced immunomodulation: impact on immune defenses against infectious disease.

It is now accepted that there are complex interactions among the central nervous system, the endocrine system, and the immune system. Although the mechanisms of this bi-directional communication is not yet fully understood, studies in the field of psychoneuroimmunology (PNI) have shown that stress, through the hypothalamic-pituitary-adrenal (HPA) and the sympathetic-adrenal medullary (SAM) axes, can induce modulation of the immune system. In this review, we discuss human studies and animal models, which focus on psychological stress and its effects on the immune defense against infectious agents, emphasizing the implications of these effects on health.

Animals↗

PubMed2003

Gonadotrophin regimens and oocyte quality in women with polycystic ovaries.

The systemic endocrine environment during the later stages of follicle development has a crucial role in co-ordinating follicular and oocyte maturation before ovulation. Polycystic ovary syndrome (PCOS) is associated with abnormal circulating hormones, abnormal peri-follicular vascularity and significant abnormalities of granulosa cell function. After induction of ovulation, fertilization rates in vivo in women with PCOS are normal, but there is an increased risk of early pregnancy loss, particularly in obese patients. After in-vitro maturation of oocytes or following ovulation induction for IVF, oocyte and embryo quality in vitro are not obviously impaired in PCOS. In some reports however, specific endocrine abnormalities, such as hyperinsulinaemia/insulin resistance, have been noted to be associated with reduced fertilization rates and abnormal early embryonic development.

Blastocyst↗

PubMed1976

Diet, nutrition, and cancer.

As the second leading cause of death in the United States, cancer is a major public health problem today. Cancer incidence varies worldwide and tends to change with migration. These epidemiological observations have led to the concept that environmental factors may be important in carcinogenesis. Diet and nutrition are receiving increased attention and the National Cancer Institute, as mandated by the Nation Cancer Act Amendments of 1974, is playing a major leadership role in expanding research efforts in the areas of environmental carcinogenesis, and nutrition in relation to cancer. The subject of diet, nutrition, and cancer is complex. Different types of cancer are not necessarily affected by dietary components in the same manner. Although the development of certain neoplasms may be repressed by specific dietary deficiencies, other types, particularly those of the liver and upper gastrointestinal tract, are actually augmented or potentiated by such deficienceis. In extrapolating results from animal experiments to humans, caution must be exercised because of possible differences in species response to the same dietary stimulus and because spontaneous tumors may react differently from experimentally-induced tumors. Diet and nutrition are viewed more appropriately as modifiers, rather than initiators, of tumorigenesis. Caloric intake, type and amount of fat, protein, amino acids, vitamins, minerals, fiber, and other dietary constituents have been studied in regard to their influence on the development of neoplasms. Dietary components may have opposing effects on tumorigenesis, i.e., protective and predisposing, and the consequence to the host will depend on the balance between these opposing forces. Studies conducted to date indicate that the modifying effect of diet and nutrition may be exerted through specific effects on 1) intestinal bacteria and substrates for bacterial metabolism, 2) microsomal mixed-function oxidase system, 3) endocrine system, 4) immunological system, 5) availability of metabolites for cell proliferations, and 6) rate of carcinogen transfer and duration of exposure to the carcinogen. More research is needed to elucidate the interaction between diet and each of these factors and to test the validity of the mechanisms proposed to explain such interactions. These studies will lead not only to a better understanding of carcinogenesis itself but also to a new understanding of the influence of diet on human physiology and metabolism.

Animals↗

PubMed1997

Effect of low-dose dopamine on serum concentrations of prolactin in critically ill patients.

Dopamine is a naturally occurring catecholamine with actions in the central nervous system and endocrine systems, including inhibition of prolactin release from the pituitary gland. Prolactin secretion has been shown to be increased in response to physiological stress, while hypoprolactinaemia is associated with a reduction in the cellular immune response. We have investigated the effects of low-dose infusion of dopamine 2.5 micrograms kg-1 min-1 on serum concentrations of prolactin in critically ill patients. Six hours after commencing the dopamine infusion, mean serum prolactin concentration had decreased from 746.95 to 128.9 mu. litre-1 (normal range 84-488 mu. litre-1). This represented a mean reduction of 79.2%, with 35% of patients exhibiting a subnormal concentration while receiving dopamine. This reduction was reversed after cessation of dopamine and reproducible on re-institution. This suppression of the release of dopamine may be a detrimental side effect of low-dose dopamine infusion in critically ill patients.

Adolescent↗

PubMed1993

Polychlorinated biphenyl exposure and human disease.

Polychlorinated biphenyls (PCBs) continue to be of great environmental and occupational health interest. This review summarizes the major clinical findings reported in individuals incurring the greatest PCB exposure--those persons working in the manufacture or repair of electrical capacitors or transformers. The potential target organs addressed in the studies reviewed include the liver, lungs, skin, cardiovascular system, nervous system, certain endocrine systems, the blood/immune system, and the gastrointestinal and urinary tracts. After careful analysis, the weight of evidence suggests the only adverse health effects attributable to high, occupational PCB exposures are dermal. This review confirms and extends the observations of others, ie, that the collective occupational experience with PCB fluids provides no evidence for adverse PCB effects on any other organ systems.

Cohort Studies↗

PubMed2006

Stressful life events and physical health.

PURPOSE OF REVIEW: This review summarizes the findings of recent researches from selected empirical and nonempirical publications focused on stressful life events and physical health. RECENT FINDINGS: The findings can be divided into biological, psychological, and social issues concerning the important relationship between stressful life events and physical health. Growing evidence in the field of psychoneuroimmunology contributes to the understanding of the mechanisms by which stressful events affect physical health. The interactions between behavior, central nervous system, and endocrine system that might cause immunosuppression is the most fascinating finding in modern medicine, and its implications are important for the prevention and treatment of somatic illnesses. Trauma, abuse, and stressful events have been studied extensively, especially among vulnerable groups such as children, women, caregivers, and combatants. Risk factors and resilience were the focus of attention of some authors as well as the behavioral intervention for coping with stressful events. SUMMARY: The findings support old observations and case reports of a close link between stressful life events and physical health and emphasize the necessity of early recognition and timely management of stress-induced illnesses. Psychosomatic approach, multidimensional diagnostics, and treatment should be sine qua non in the integrated care of affected people and should improve their quality of life.

Brain↗