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Vitamin D endocrine system and the genetic susceptibility to diabetes, obesity and vascular disease. A review of evidence.

The Vitamin D endocrine system regulates multiple aspects of calcium metabolism and cellular differentiation and replication in the immune system, endocrine pancreas, liver, skeletal muscles and adipocytes. It plays an important role in glucose homeostasis, notably, in the mechanism of insulin release. Actions of vitamin D are mediated by the binding of 1, 25-(OH)2D3 to a specific cytosolic/nuclear vitamin D receptor (VDR), a member of the steroid/thyroid hormone receptor superfamily. Several frequent polymorphisms are found in the VDR gene and were reported to be associated with a variety of physiological and pathological phenotypes in many populations. In this paper, we will review the evidences suggesting associations of allelic variations in the VDR gene and phenotypes related to body weight, glucose homeostasis, diabetes and its vascular complications.

Diabetes Mellitus↗

Qualitative mathematical models of endocrine systems.

Some qualitative dynamical models of endocrine systems are considered and analyzed, with the reproductive endocrine system as an example. The models considered are systems of nonlinear ordinary differential equations describing the rates of change of the hormonal concentrations with time. This type of general approach, which requires only the incorporation of the basic qualitative features of the interactions present in the underlying system into the model, is a potentially powerful tool for elucidating possible mechanisms for observed qualitative patterns of hormonal dynamics.

Animals↗

The endocrine system in diabetes mellitus.

The pathophysiology of diabetes mellitus is complex and not fully understood. However, it emerges as an abnormal metabolic condition associated with a systemic damage to the vascular bed. Cumulative evidence also reveals that the endocrine system is not intact in patients with diabetes mellitus. It is not clear whether the changes observed in the endocrine system represent a primary defect or reflect the effects of the impaired insulin action and abnormal carbohydrate and lipid metabolism on the hormonal milieu. Review of the literature reveals that the function of the entire endocrine system including the functions of hormones from the hypothalamus, pituitary, adrenal, thyroid, parathyroid, the vitamin D system, the gonads, and the endocrine function of the adipose tissue, is impaired. Good metabolic control and insulin treatment may reverse some of these abnormalities. It remains unanswered as to what extent these changes in the endocrine system contribute to the vascular pathologies observed in individuals affected by diabetes mellitus and whether part of the abnormalities observed in the endocrine system reflect a basic cellular defect in the diabetic syndrome.

Diabetes Mellitus, Type 1↗

[Tuberculosis of the endocrine system].

Tuberculosis now rarely affects the endocrine system. Adrenal tuberculosis is responsible for Addison's disease, but now fewer cases are affected. Although the symptoms and signs of Addison's disease appear when most of the adrenal glands have been functionally destroyed, adrenal tuberculosis results in not only chronic adrenal insufficiency but also acute adrenal failure. Dissemination of M. tuberculosis is responsible for adrenal tuberculosis, other tuberculous lesions (including the past lesions) should be evaluated. Bilateral adrenal calcification and/or enlargement which are often pointed out on abdominal CT, are important signs of adrenal tuberculosis. Thyroid gland is rarely affected, but thyroid function impairment is uncommon even if it is affected. Hypopituitarism due to intracranial tuberculoma or tuberculous meningitis are also reported. Tuberculosis of the endocrine system is a part of disseminated infection, so it should not be overlooked in miliary spread tuberculosis.

Adrenal Gland Diseases↗

Endocrine-paracrine interaction in communication between the immune and endocrine systems. Activation of the hypothalamic-pituitary-adrenal axis in inflammation.

There are bidirectional communications between the immune and endocrine systems. Cytokines produced in inflammatory foci cause changes in the endocrine system, including activation of the hypothalamic-pituitary-adrenal (HPA) axis. Hormones produced in the endocrine system, especially glucocorticoids, affect the immune system to modulate its function. This is an important endocrine system for the defence mechanism. In addition, bacterial lipopolysaccharide produces cytokines in the brain and endocrine organs which are considered to act through the paracrine mechanism to regulate the HPA axis. Endocrine-paracrine interaction is important for the defence mechanism of the organism.

Animals↗

The endocrine system and ageing.

Complex changes occur within the endocrine system of ageing individuals. This article explores the changes that occur in the metabolism and production of various hormones and discusses the resulting clinical consequences. As individuals age there is a decline in the peripheral levels of oestrogen and testosterone, with an increase in luteinizing hormone, follicle-stimulating hormone and sex hormone-binding globulin. Additionally there is a decline in serum concentrations of growth hormone, insulin-like growth factor-I and dehydroepiandrosterone and its sulphate-bound form. Even though there are complex changes within the hypothalmo-pituitary-adrenal/thyroid axis, there is minimal change in adrenal and thyroid function with ageing. The clinical significance of these deficiencies with age are variable and include reduced protein synthesis, decrease in lean body mass and bone mass, increased fat mass, insulin resistance, higher cardiovascular disease risk, increase in vasomotor symptoms, fatigue, depression, anaemia, poor libido, erectile deficiency and a decline in immune function. For each endocrine system, studies have been carried out in an attempt to reverse the effects of ageing by altering the serum hormonal levels of older individuals. However, the real benefits of hormonal treatment in older individuals are still being evaluated.

Aging↗

Comparative immunohistochemical study of the gastroenteropancreatic endocrine system of three reptiles.

The gastroenteropancreatic (GEP) endocrine system of three reptiles, Testudo graeca, Mauremys caspica, and Lacerta lepida, was investigated by means of immunocytochemistry. Single and double immunostaining methods have demonstrated immunoreactivity for insulin, glucagon, pancreatic polypeptide (PP), somatostatin, serotonin, and peptide tyrosine tyrosine (PYY) in endocrine cells of the pancreas of the reptiles studied. Islet-like structures with insulin-immunoreactive (IR) cells surrounded by glucagon-IR cells were observed only in the splenic portion of the pancreas of M. caspica. Occasionally, somatostatin- and PP-IR cells were associated with glucagon-containing cells. Endocrine cells were also observed in the excretory ducts of the exocrine glands. Serotonin, bombesin, neurotensin, gastrin, glucagon, somatostatin, PYY, and insulin were demonstrated immunocytochemically in open-type GEP cells of the digestive tract of the animals studied. Serotonin, somatostatin, and glucagon-immunoreactive cells were the most abundant endocrine cell types. In L. lepida, PP- and peptide tyrosine tyrosine-immunoreactive cells were also frequently observed. Cells containing cholecystokinin, gastric inhibitory peptide, met- and leu-enkephalin, motilin, secretin, and vasoactive intestinal peptide could not be detected. The present work demonstrates that the reptilian GEP endocrine system is a complex structure containing most of the regulatory peptides similar in structure to those found in higher vertebrates.

Animals↗

The influence of chlormethiazole on the neuro-endocrine system in chronic alcoholics.

The neuro-endocrine system is affected by chronic ethanol ingestion. Chlormethiazole is effective in the treatment of the ethanol withdrawal syndrome because of its tolerability, lack of hepatotoxicity, short plasma half-life, lack of any long-acting intermediate metabolites and lack of adverse effects on the neuro-endocrine system in alcoholics.

Alcoholism↗

The immunological functions of the vitamin D endocrine system.

The discoveries that activated macrophages produce 1alpha25-dihydroxyvitamin D3 (1alpha,25-(OH)2D3), and that immune system cells express the vitamin D receptor (VDR), suggested that the vitamin D endocrine system influences immune system function. In this review, we compare and contrast how 1alpha,25-(OH)2D3 synthesis and degradation is regulated in kidney cells and activated macrophages, summarize data on hormone receptor function and expression in lymphocytes and myeloid lineage cells, and discuss how locally-produced 1alpha,25-(OH)2D3 may activate a negative feed-back loop at sites of inflammation. Studies of immunity in humans and animals lacking VDR function, or lacking vitamin D, are viewed to gain insight into the immunological functions of the vitamin D endocrine system. The strong associations between poor vitamin D nutrition, particular VDR alleles, and susceptibility to chronic mycobacterial infections, together with evidence that 1alpha,25-(OH)2D3 served as a vaccine adjuvant enhancing antibody-mediated immunity, suggest a model wherein high levels of 1alpha,25-(OH)2D3-liganded VDR transcriptional activity may promote the CD4+ T helper 2 (Th2) cell-mediated and mucosal antibody responses to cutaneous antigens in vivo. We also review a diverse and rapidly growing body of epidemiological, climatological, genetic, nutritional and biological evidence indicating that the vitamin D endocrine system functions in the establishment and/or maintenance of immunological self tolerance. Studies done in animal models of multiple sclerosis (MS), insulin-dependent diabetes mellitus (IDDM), inflammatory bowel disease (IBD), and transplantation support a model wherein the 1alpha,25-(OH)2D3 may augment the function of suppressor T cells that maintain self tolerance to organ-specific self antigens. The recent progress in infectious disease, autoimmunity and transplantation has stimulated a gratifying renaissance of interest in the vitamin D endocrine system and its role in immunological health.

Autoimmune Diseases↗

Caste-specific maturation of the endocrine system in the female honey bee larva.

The endocrine system of female honey bee larvae has been studied through postembryonic development with histological and autoradiographic techniques. During larval development, brain and retrocerebral complex proceed from immature cells to an active endocrine system. Caste-specific retardation occurs in the worker during this process. In the developing queen, the differentiation of the neurosecretory cells (NSC) and the outgrowth of their axons occurs from the second instar onward and is nearly completed in the fourth, whereas in the worker larva these processes are delayed by more than one instar. In the queen, RNA synthesis starts in the NSC at the end of the third instar and in the worker at the fifth instar. Stainable neurosecretory material is present only in fifth instar queen larvae. The queen's corpora cardiaca become active at the end of the fourth, those of the worker in the fifth instar. In the corpora allata (CA), nuclei undergo several phases of endomitosis. These phases of polyploidization end at the beginning (queen) or at the end (worker) of the fifth instar respectively. CA volume in the queen is twice that of a worker at its height at the end of larval development. these data demonstrate a caste-specific maturation of the endocrine organs which results in differences in hormone titres.

Animals↗

The vitamin D endocrine system.

In this review I have discussed out current understanding of the vitamin D endocrine system. Vitamin D is made available to the body both by intestinal absorption and by photosynthesis in the skin. To be active, vitamin D must be hydroxylated to 250HD, principally in the liver, and to 1,25(OH)2D and 24,25(OH)2D, principally in the kidney. The best studied target tissues for the vitamin D metabolites are bone, kidney, and intestine. However, the list of additional potential target tissues is expanding and includes muscle, endocrine pancreas, parathyroid gland, pituitary, and skin. Disorders of the vitamin D endocrine system can be categorized into three groups: decreased bioavailability, abnormal metabolism, and aberrant target tissue response. A number of illustrative examples for each category have been discussed. Primary biliary cirrhosis typifies the problem of vitamin D malabsorption and disrupted enterohepatic circulation; chronic renal failure is the most devastating problem of vitamin D metabolism; and vitamin D dependent rickets type II is the best example of aberrant target tissue response. However, certain disorders overlap these distinct categories. Others, such as the nephrotic syndrome, which leads to urinary losses of the vitamin D metabolites (presumably bound to DBP), are not readily categorized. Nevertheless, an understanding of the level at which the vitamin D endocrine system is perturbed by any given disorder provides a rational basis for therapeutic intervention.

Aged↗

Age and the endocrine system.

The pattern of age-induced changes in each endocrine system is unique. Both hormone levels and target organ responsivity are altered in the aging endocrine-cardiovascular system. Serum levels of vasopressor hormones both increase (norepinephrine) and decrease (renin, aldosterone). Target organ responses to beta-adrenergic stimulation in the heart and probably also in vascular smooth muscle decrease due to postreceptor changes. These effects contribute to the clinical problems of hypertension and orthostatic hypotension which characterize the elderly. Aging produces mild carbohydrate intolerance and a minimal increase in fasting serum glucose in healthy, nonobese individuals, primarily due to decreasing postreceptor responsiveness to insulin. Aging decreases the metabolism of thyroxine, including its conversion to triiodothyronine, but clinically significant alterations of thyroid hormone levels do not occur. Changes in the end-organ response to thyroid hormones, however, significantly alter the clinical presentation of thyroid diseases. Aging shifts the serum vasopressin-serum osmolality relationship toward higher serum vasopressin levels probably due to altered baroreceptor input, probably contributing to the tendency toward hyponatremia in the elderly. Aging slows the metabolism of cortisol, but glucocorticoid levels in the human are essentially unaltered by age. However, recent data indicate that delta-5 adrenal steroids decrease markedly in both men and women. Nodules in the anterior pituitary, the thyroid, and the adrenal increase in frequency with aging. Finally, the reproductive system is primarily altered by endocrine cell death, by unknown mechanisms, resulting in decreased estrogen and testosterone levels in women and men. This most obvious age-related endocrine change turns out to be incompletely understood and is not representative of most age-related endocrine changes. Despite characterization of these many age-related alterations in endocrine systems, therapeutic issues often remain unexplored, and more data are needed in many areas.

Adrenal Glands↗

[Mechanism of impairment of calcium metabolism caused by toxin T-2; the role of the vitamin D-dependent endocrine system].

Functions of the vitamin D-dependent endocrine system were studied in rats deprived of the vitamin after administration of T-2 toxin. Impairments of calcium metabolism, alterations in the enzymatic activity related to vitamin D3 bioactivation and receptor binding of the hormonal form 1,25(OH)2D3 were similar both in rats deprived of vitamin D, treated with T-2 toxin within 5 days at a dose of 0.54 mg/kg and in the corresponding controls. At the same time, reduction of the calcium metabolism patterns was retarded in rats obtaining vitamin D3 simultaneously with T-2 toxin. This effect was expressed as a decrease in normalization of 25-OHD concentration in blood, absence of renal I-hydroxylase 25-OHD3 activation, inspite of the higher content of parath hormone in blood and of cAMP in kidney, while concentration of bound 1,25(OH)2D3 receptors was distinctly decreased in tissues-targets in vivo. Thus, the effects of T-2 toxin on the vitamin D-dependent endocrine system were manifested as development of the vitamin, secondary deficiency, as resistance of I-hydroxylase 25OHD3 to regulating effect of parath hormone as well as inhibition of interaction between the complexes 1,25(OH)2D3-receptor and chromatin.

Animals↗

[Regulation of the endocrine system].

The universal significance of the endocrine system for the regulation of the vital functions and the extra ordinarily high biological activity of the hormones require sensitive mechanisms of regulation within this system. The central nervous system is integrated into these regulatory processes and controls by neurotransmitters and hypothalamic releasing and inhibiting of the hormones the secretion of the hypophyseal and peripheral hormones. Central and peripheral feed-back mechanisms making possible the adaptation of the neuroendocrine system to changing external and internal conditions are operative between the peripheral endocrine glands and the hypothalamo-hypophyseal system as well as during synthesis, transport, action and metabolism of hormones. The knowledge of the fundamental regulatory mechanisms is a presupposition for the effective diagnosis and therapy of endocrine dysfunctions.

Endocrine Glands↗

The vitamin D Endocrine system: manipulation of structure-function relationships to provide opportunities for development of new cancer chemopreventive and immunosuppressive agents.

Biological responses mediated by vitamin D occur as a consequence of the integrated actions of the vitamin D endocrine system. The vitamin D endocrine system is characterized by the sequential two-step metabolism of vitamin D to 1 alpha,25(OH)2D3 by the liver and kidney, and by the ability to generate biological responses in over 30 target tissues through nuclear receptor (nVDR) regulation of gene transcription and nongenomic pathways. It is now clear that the vitamin D endocrine system embraces many more target tissues than simply the intestine, bone and kidney. Notable additions to this list of tissues containing the nVDR include pancreatic B cells, pituitary gland, breast tissue, placenta, lymphocytes, keratinocytes, colon, and prostate, as well as many cancer cell lines. In addition to the classical actions of 1 alpha,25(OH)2D3 on mediating calcium homeostasis, this seco steroid has been identified as a potent stimulator of cell differentiation as well as an inhibitor of proliferation. Over the past decade at least 400 analogs of 1 alpha,25(OH)2D3 have been chemically synthesized and their biological properties systematically explored in a variety of assays which quantified both their calcemic effects and cell differentiating potential. The objective has been to identify new analogs devoid of the classical calcemic consequences of high doses of 1 alpha,25(OH)2D3, namely hypercalcemia, soft tissue calcification and nephrocalcinosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗