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Circulating versus local renin-angiotensin system in cardiovascular homeostasis.

The renin-angiotensin system has traditionally been viewed as an endocrine system. Recent data demonstrate that renin and angiotensinogen genes and their products are expressed at many local tissue sites. The concept that multiple tissues synthesize angiotensin has changed our understanding of the physiology of the renin-angiotensin system. These potential autocrine-paracrine systems may be important in the regulation of local tissue functions in addition to the circulating endocrine system. The activity of the tissue system under different conditions can influence the pharmacologic response to inhibitors of the renin-angiotensin system. For example, evidence suggests that tissue angiotensin-converting enzyme (ACE) may be the primary site of action of ACE inhibitors. Consequently, the duration of action of an ACE inhibitor may be more dependent on the duration of tissue ACE inhibition than on the drug's serum half-life. The differential effects of these pharmacologic inhibitors on the tissue renin-angiotensin systems may form the basis of differentiation between the various ACE inhibitors.

Angiotensin-Converting Enzyme Inhibitors↗

Organotin compounds promote adipocyte differentiation as agonists of the peroxisome proliferator-activated receptor gamma/retinoid X receptor pathway.

Nuclear receptors play important roles in the maintenance of the endocrine system, regulation of organ differentiation, and fetal development. Endocrine disruptors exert their adverse effects by disrupting the endocrine system via various mechanisms. To assess the effects of endocrine disruptors on nuclear receptors, we developed a high-throughput method for identifying activators of nuclear receptors. Using this system, we found that triphenyltin and tributyltin were activators of peroxisome proliferator-activated receptor (PPAR) gamma and retinoid X receptor. Because PPARgamma is a master regulator of adipocyte differentiation, we assessed the effect of organotin compounds on preadipocyte 3T3-L1 cells. We found that organotin compounds stimulated differentiation of 3T3-L1 cells as well as expression of adipocyte marker genes.

3T3 Cells↗

[The renin-angiotensin-aldosterone (RAA) system in endocrine diseases].

Modern, views are presented on the pathogenesis of arterial hypertension in certain diseases of endocrine glands. In patients with phaeochromocytoma, virilizing tumours, acromegaly, in Cushing's disease, and in Conn's syndrome at the present state of knowledge it is not possible to formulate unequivocal conclusions concerning the effects of renin-angiotensin-aldosterone system on the mechanism of arterial hypertension development in these endocrinopathies.

Adrenal Gland Neoplasms↗

Molecular aspects of the endocrine tumours of the pancreas and the gastrointestinal tract.

Neuroendocrine tumours of the gastroenteropancreatic tract are growths originating either from the cells of the diffuse (neuro)endocrine system, such as gastric carcinoids and islet cell tumours, or from nerve structures, such as duodenal paragangliomas. A great deal of cellular and clinical information is available whereas data concerning the genetic and molecular basis of diffuse (neuro)endocrine system tumours of the gastroenteropancreatic tract are very few and fragmentary. The present paper reviews some genetic and molecular investigations of potential interest. As far as concerns the genetic background of diffuse (neuro)endocrine system tumours, the frequent loss of heterozygosity for the locus of Multiple Endocrine Neoplasia type 1 in tumour samples suggests a potential role of the Multiple Endocrine Neoplasia gene. With regard to the molecular background, no mutation of the p53 or retinoblastoma susceptibility (Rb) genes has been demonstrated. Useful data have been generated by in situ analysis of the proliferation activity of tumours.

Female↗

Endurance exercise training and reproductive endocrine dysfunction in men: alterations in the hypothalamic-pituitary-testicular axis.

Research indicates that endurance exercise training has significant effects upon the reproductive endocrine system of humans. Until recently, this effect was thought to be limited primarily to women. However, a growing body of evidence demonstrates that the male reproductive endocrine system is also effected. Specifically, the circulating hormonal levels of testosterone are found to be at low concentrations; and, the hypothalamic-pituitary-testicular axis that regulates testosterone production is altered in endurance trained men. The physiological mechanism inducing the lower testosterone is currently unclear; but in many respects, these men display hypogonadotropic hypogonadism characteristics. Currently, the time course of the changes in the reproductive endocrine system is unresolved and in need of much furthers scientific investigation. The evidence available, however, suggests that a slowly developing process requiring years of exercise training results in these changes. Potentially, the lowered testosterone levels of the endurance-trained male could disrupt some of their anabolic or androgenic dependent processes. To date, there are only a limited number of findings suggesting that a consistent disruption of testosterone dependent processes occur due to endurance exercise training (e.g., oligo-spermatogenesis). Conversely, the alterations in testosterone concentration brought about by endurance training could have cardiovascular protective effects and thus be beneficial to the health of these men.

Exercise↗

Employment of the human estrogen receptor beta ligand-binding domain and co-activator SRC1 nuclear receptor-binding domain for the construction of a yeast two-hybrid detection system for endocrine disrupters.

To screen a wide variety of chemicals for endocrine disrupters, and to develop an effective microbial degradation system for them, a good system is needed for the rapid and accurate evaluation of the endocrine-disrupting activities of suspected chemicals and their degradation products. We constructed two-hybrid systems that co-express the Gal4p DNA binding domain/ligand-binding domain of human estrogen receptor (hER) alpha or beta and the Gal4p transactivation domain/nuclear receptor-binding domain of co-activator SRC1, TIF2, or AIB1 in Saccharomyces cerevisiae with a chromosome-integrated lacZ reporter gene under the control of Gal4p-binding sites. We found that the combination of the hERbeta ligand-binding domain and SRC1 nuclear receptor-binding domain was most effective for the xenoestrogen-dependent induction of reporter activity. The extent of transcriptional activation by known xenoestrogens and phytoestrogens was found to correlate well with their estrogenic activities as measured by the previous system with rat ERalpha. This system detects estrogenic activity in some chemicals that have not been suspected of being positive. We also applied this assay system to test the microbial degradation products of gamma-hexachlorocyclohexane (gamma-HCH) by Sphingomonas paucimobilis. Among the gamma-HCH metabolites, 2,5-dichlorohydroquinone and chlorohydroquinone had estrogenic activities similar to the original chemical, while hydroquinone, a later stage metabolite, showed no activity, suggesting the necessity of evaluating intermediate metabolites in microbial degradation systems.

Endocrine Glands↗

[Regularities of cytogenesis in the endocrine gastroenteropancreatic system in vertebrates].

This paper reviews the literature data and the results of authors' own investigations on cytogenesis of endocrine cells of gastro-entero-pancreatic (GEP-) system in vertebrate animals and man. In pancreas two groups of sources of endocrine cell development were distinguished including both intra- and extrainsular. In cytogenesis of mucosal endocrine cells in gastrointestinal tract (GIT) the major role belongs to the stem cells which differentiate through the stage of committed precursors ("agranular cells"). Pancreas and GIT epithelium are characterized by the formation of endocrine cells from exocrine ones. The data presented provide the indication of the endodermal origin of endocrine cells of GEP-system.

Animals↗

Genetics and biology of vitamin D receptor polymorphisms.

The vitamin D endocrine system is involved in a wide variety of biological processes including bone metabolism, modulation of the immune response, and regulation of cell proliferation and differentiation. Variations in this endocrine system have, thus, been linked to several common diseases, including osteoarthritis (OA), diabetes, cancer, cardiovascular disease, and tuberculosis. Evidence to support this pleiotropic character of vitamin D has included epidemiological studies on circulating vitamin D hormone levels, but also genetic epidemiological studies. Genetic studies provide excellent opportunities to link molecular insights with epidemiological data and have therefore gained much interest. DNA sequence variations, which occur frequently in the population, are referred to as "polymorphisms" and can have modest and subtle but true biological effects. Their abundance in the human genome as well as their high frequencies in the human population have made them targets to explain variation in risk of common diseases. Recent studies have indicated many polymorphisms to exist in the vitamin D receptor (VDR) gene, but the influence of VDR gene polymorphisms on VDR protein function and signaling is largely unknown. So far, three adjacent restriction fragment length polymorphisms for BsmI, ApaI, and TaqI, respectively, at the 3' end of the VDR gene have been the most frequently studied. Because these polymorphisms are probably nonfunctional, linkage disequilibrium with one or more truly functional polymorphisms elsewhere in the VDR gene is assumed to explain the associations observed. Research is therefore focussed on documenting additional polymorphisms across the VDR gene to verify this hypothesis and on trying to understand the functional consequences of the variations. Substantial progress has been made that will deepen our understanding of variability in the vitamin D endocrine system and might find applications in risk assessment of disease and in predicting response-to-treatment.

Chromosomes, Human, Pair 12↗

Hormone replacement in the aging male?.

The recent increase in the elderly population, current health trends, and awareness of age-related changes in the male endocrine system have led to discussions about the endocrine system being a "pacemaker" of male aging. Better prevention and treatment of "non-beneficial states of health" in aging men, such as generally decreased well-being and virility, increased visceral fat, osteopenia, atherosclerosis, and impaired cognitive function, is based on improved understanding of aging, particularly the significance of age-associated hormonal changes. Although not as dramatic as in women, men also show declining hormone serum concentrations with aging (Vermeulen and Kaufman, 1995). Because aging is associated with deleterious effects resembling the clinical signs of hypogonadism or states of subnormal hormone concentrations, the potential role of hormone supplementation in aging men paralleling hormone replacement therapy in postmenopausal women is the topic of discussion. The goal of hormone replacement would be to improve body composition and increase muscle strength and quality of life in men, thereby reducing mortality and morbidity. The findings so far support the need for long-term studies of hormonal supplementation in older males showing decreased hormone serum levels. Nevertheless, to date, such a use outside the context of a clinical trial is not justified.

Aging↗

Endocrine dismodulation and cancer.

OBJECTIVE: Carcinogenesis has generally been viewed as a genomic disease resulting from genetic mutations occurring at critical locations in the genome in a particular sequence. In the last 10 years, scientists have increasingly identified changes in the levels, frequency and types of endocrine hormones as important contributors to the major cancers faced by western populations such as breast cancer (estrogen, progesterone, prolactin), prostate cancer (estrogen, testosterone), endometrial cancer (estrogen) and thyroid cancer (TSH, T3, T4). This manuscript summarizes cancer mechanisms linked to changes in endocrine function and discusses tools for analyzing and understanding the associated data. DISCUSSION: A number of chemicals in the environment mimic the role of hormones to bind to receptors (e.g. phytoestrogens as estrogen mimics), alter signaling pathways (e.g. retinoids), inhibit steroid hormone synthesis (such as some fungicides) or alter steroid hormone metabolism (such as TCDD altering the metabolism of both estrogen and thyroid hormones). Genomic and non-genomic endocrine signaling pathways are extensively present in the body and function in a complicated fashion. In order to fully understand the basis for endocrine-induced cancers, one must simultaneously study the various receptors, ligands, enzymes, other proteins within different organs which all contribute to endocrine system function. Also, cross-talk between endocrine systems is common and is key to understanding a potential role of light-dark cycles on human cancer risks. CONCLUSION: Mechanism-based mathematical models are the only analysis tool available to address all aspects of these complicated networks.

Animals↗

[Molecular basis of the communication of the nervous, endocrine and immune systems].

The nervous, endocrine and immune systems integrate one another to preserve homeostasis in the stress response. The molecular bases of this network are reviewed. The neuroendocrine actions of cytokines, the immune activities of pituitary hormones, opioids, glucocorticoids as well as the immune system production of opioid peptides are examined in detail.

Adrenocorticotropic Hormone↗

Relationship between fatty acids and the endocrine and neuroendocrine system.

Significant interactions exist between fatty acids and the endocrine system. Dietary fatty acids alter both hormone and neuropeptide concentrations and also their receptors. In addition, hormones affect the metabolism of fatty acids and the fatty acid composition of tissue lipids. The principal hormones involved in lipid metabolism are insulin, glucagon, catecholamines, cortisol and growth hormone. The concentrations of these hormones are altered in chronic degenerative conditions such as diabetes and cardiovascular disease, which in turn leads to alterations in tissue lipids. Lipogenesis and lipolysis, which modulate fatty acid concentrations in plasma and tissues, are under hormonal control. Neuropeptides are also involved in lipid metabolism in brain and other tissues. Polyunsaturated fatty acids are also precursors for eicosanoids including prostaglandins, leucotrienes, and thromboxanes, which have hormone-like activities. Fatty acids in turn affect the endocrine system. Saturated and trans fatty acids decrease insulin concentration leading to insulin resistance. In contrast, polyunsaturated fatty acids increase plasma insulin concentration and decrease insulin resistance. In humans, omega3 polyunsaturated fatty acids alter the levels of opioid peptides in plasma. Free fatty acids have been reported to inhibit glucagon release. Fatty acids also affect receptors for hormones and neuropeptides.

Animals↗

Light and life--facts and research perspectives at the Cologne Light Symposium 2002.

The international meeting Light, Endocrine Systems and Cancer--Facts and Research Perspectives was convened because recent research suggests that ubiquitous light may have more serious cancer consequences than expected. Beyond the established causal link between (over) exposure to sunlight and skin cancer, many scientists consider a causal relationship between light, endocrine systems and internal cancers as biologically plausible. To identify options to turn biological plausibility of mechanisms into true understanding and to assess the possible public health relevance we chose to bring together leading specialists from clinical, experimental laboratory and epidemiological studies of these issues to stimulate a critical, multi-disciplinary discussion of published and new results. Presentations at the symposium covered the physics of light and evolutionary aspects and provided intriguing information about chronobiology, physiology and patho-physiology of endocrine systems and carcinogenesis. Experimental and epidemiological findings on light and skin cancer, and of very recent investigations of relationships between light and internal cancers such as breast cancer were presented. The meeting concluded with a lively discussion of future research options. The symposium's essence and constructive atmosphere are captured in these proceedings [Neuroendocrinol Lett 2002 Jul;23 Suppl 2:1-104] which contain: (i) original presentation papers [Vladimir Anisimov, David Blask, Roland Böni, George Brainard, Thomas Erren, Alexander Lerchl, Sidney Perkowitz, Chris Portier, Russel Reiter, Richard Stevens, Günter Vollmer]; (ii) abstracts of oral and poster presentations; (iii) four commentaries [Charles Poole, Chris Portier, Till Roenneberg and Rob Lucas, Vladimir Anisimov and Johnni Hansen] on the presentations at the meeting and possible implications for research and public health. In our view, the biological plausibility of mechanistic links between light and hormones and cancer can serve as a unique basis for syn-disciplinary research and we expect that investigations in this area will become a higher priority research focus.

Congresses as Topic↗

Evolutionary origins of intercellular communication systems: implications for mammalian biology.

Traditionally, the two major systems of intercellular communication (i.e. the nervous and endocrine systems) were considered separate functional and anatomical entities. Recent studies have provided evidence that the biochemical elements of these systems have common early phylogenetic origins and have suggested that, with the exception of their anatomical diversity, all the systems of intercellular communication are biochemically similar. On the basis of these findings, we suggest that the overlaps between the nervous and endocrine systems, the widespread tissue production of hormones, and other phenomena are now more easily understood.

Animals↗

Differentiation-associated Na+-dependent inorganic phosphate cotransporter (DNPI) is a vesicular glutamate transporter in endocrine glutamatergic systems.

Vesicular glutamate transporter is present in neuronal synaptic vesicles and endocrine synaptic-like microvesicles and is responsible for vesicular storage of L-glutamate. A brain-specific Na(+)-dependent inorganic phosphate transporter (BNPI) functions as a vesicular glutamate transporter in synaptic vesicles, and the expression of this BNPI defines the glutamatergic phenotype in the central nervous system (Bellocchio, E. E., Reimer, R. J., Fremeau, R. T., Jr., and Edwards, R. H. (2000) Science 289, 957-960; Takamori, S., Rhee, J. S., Rosenmund, C., and Jahn, R. (2000) Nature 407, 189-194). However, since not all glutamatergic neurons contain BNPI, an additional transporter(s) responsible for vesicular glutamate uptake has been postulated. Here we report that differentiation-associated Na(+)-dependent inorganic phosphate cotransporter (DNPI), an isoform of BNPI (Aihara, Y., Mashima, H., Onda, H., Hisano, S., Kasuya, H., Hori, T., Yamada, S., Tomura, H., Yamada, Y., Inoue, I., Kojima, I., and Takeda, J. (2000) J. Neurochem. 74, 2622-2625), also transports L-glutamate at the expense of an electrochemical gradient of protons established by the vacuolar proton pump when expressed in COS7 cells. Molecular, biological, and immunohistochemical studies have indicated that besides its presence in neuronal cells DNPI is preferentially expressed in mammalian pinealocytes, alphaTC6 cells, clonal pancreatic alpha cells, and alpha cells of Langerhans islets, these cells being proven to secrete L-glutamate through Ca(2+)-dependent regulated exocytosis followed by its vesicular storage. Pancreatic polypeptide-secreting F cells of Langerhans islets also expressed DNPI. These results constitute evidence that DNPI functions as another vesicular transporter in glutamatergic endocrine cells as well as in neurons.

Adenosine Triphosphate↗

The MEA-I syndrome: an all or none phenomenon?

Studies of two kindreds with the MEA-I syndrome prompted us to challenge the long-standing concept that endocrine involvement in this syndrome may be limited to one or two endocrine glands. Evaluation of medical histories, autopsies, or biochemical screening of 72 family members from five generations suggests that individuals inheriting the trait will develop endocrinopathy in all three endocrine systems characteristically involved in this syndrome, i.e., parathyroids, islets of Langerhans, and pituitary. Thirty-six surgical procedures have been performed on 21 family members. Gastrointestinal bleeding was the cause of death in 10 of 11 affected individuals. Only two individuals who inherited the trait have lived beyond 54 years, one with a total gastrectomy and one taking Cimetidine. In each instance, when tissue from one of the three endocrine systems was obtained (surgery or autopsy), abnormalities were documented. A search of the English-language literature (1953 to 1978) for reports of complete autopsies of MEA-I-affected individuals indicated pathology in all three endocrine systems in 29 of 32 cases. Medical and surgical management of this inherited disorder should be based on the concept that pathological changes will develop in the parathyroids, pancreatic islets, and the pituitary.

Adrenal Gland Neoplasms↗

[Relation and interactions between the immune and neuroendocrine systems].

For far too long, the immune system has been viewed in isolation from the rest of the body's organ system. But now it is clear that the immune system is an integral part of the organ and physiological systems of whole organism. Especially, the immune and endocrine systems share many ligands and receptors that result in constant and important bidirectional communication. A new and important function for the immune system is to serve as a sensory organ for noncognitive stimuli such as infectious agents and tumours. On the other hand the neuroendocrine system can perform important immunoregulatory activities. It also suggest that brain is not more an immunologically privileged site. Recent studies provide a new view of immunoreactivity to antigens from the nervous system and to immune and inflammatory responses in brain. These may be influenced both by the circulating cytokines derived from the immune system and/or those endogenously produced within the neuroendocrine system. There is a growing body of evidence that cytokines are an integral part of the central nervous system with an important neuromodulatory role in neural mechanisms regulating stress responses, hormonal changes and various kinds of behavior. The mutual informatory circuit inside of the immune, nervous and endocrine systems suggest that they all form the superinformation system with pivotal regulatory role in living organisms. Overall, the recognition of the immune system as our sixth sense may ultimately provide the new understanding of physiology required for successful diagnostic and therapeutic programs against disease and stress involving immune-neuroendocrine communication. (Tab. 5, Ref. 35.)

Animals↗