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Journal Article 2002; 23(4): 315-320 PubMed PMID: 12195233 Citation  Keywords:  Animals, Genes, Immediate-Early:physiology, Hypothalamus:cytology, Male, Neurons:physiology, Physical Stimulation, Proto-Oncogene Proteins c-fos:genetics, Rats, Rats, Sprague-Dawley, Skin:radiation effects,.   

OBJECTIVES: The purpose of this study was to determine: 1) The spatial pattern of c-fos gene expression in rat hypothalamic neurons after exposure to NMS and 2) The expression of c-fos gene after combined exposure to NMS and EHF irradiation of the rat skin.

METHODS: The experiments were performed on 28 male adult Sprague-Dawley rats. After rats were subjected to noxious mechanical stimulation (NMS) or its combination with EHF irradiation of the skin, cells in various hypothalamic structures were analyzed to determine theirs effects on c-fos gene expression, an accepted marker of the activation of neurons. C-Fos-like protein was revealed by an indirect immunoperoxidase method.

RESULTS: This study revealed that NMS stimulates c-fos gene expression in the anterior hypothalamic nucleus (AHN), dorsomedial hypothalamic nucleus (DMH), ventromedial hypothalamic nucleus (VMH), and lateral hypothalamic area (LHA) by 157, 101, 199 and 115% respectively compared to control animals. Combined exposure to NMS and EHF irradiation directed at the skin in the region of the St36 acupuncture point projection site (left side) results in a decrease of the number of neurons that are activated in the AHN, DMH, VMH, and LHA by 33.6, 13.2, 31.0 and 32.9% respectively compared to the number of neurons activated by exposure to NMS by itself. EHF exposure of the skin of rats not subjected to NMS differentially effects the number of c-Fos positive cells expressed in hypothalamic structures: a decrease of 39.7% was observed in the number of activated neurons in the central part of LHA (level 28) compared to sham-irradiated animals, while an increase of 80.95% was noted in the number of c-Fos positive cells in the DMH compared to sham-irradiated animals.

CONCLUSIONS: The spatial pattern and degree of activation of c-fos gene expression has been shown in cells of the hypothalamus of rats after exposure to NMS by itself and after NMS combined with EHF irradiation of the skin. The "stress" reaction of cells in specific hypothalamic structures has been shown to be decreased after EHF exposure of the skin....

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Letter 2002; 23(4): 287-288 PubMed PMID: 12195227 Citation  Keywords:  Animals, Genes, Fungal:physiology, Homosexuality, Humans, Pheromones:physiology, Rodentia, Vomeronasal Organ:physiology, Yeasts:physiology,.   

: Pheromones and their receptors are the molecules used by very different organisms in order to join two haploid cells. It happens evidently in yeast, since the two blending haploid cells are also the two mating organisms, whereas in rodents pheromone receptors are the triggers of the vomeronasal system which, supervising sexual behaviors, is responsible for copulation and therefore for fertilization. The debate is still open about the real significance of pheromones in humans but a working vomeronasal organ, able to recognize pheromones of the same sex, could be the simplest biological explanation of homosexuality. This hypothesis is discussed and connected with some well known experimental data....

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Journal Article 2002; 23(4): 273-280 PubMed PMID: 12195224 Citation  Keywords:  Animals, Humans, Pituitary Gland, Posterior:physiology, Receptors, Purinergic:physiology,.   

: The neurohypophysis is an original model of the CNS secretory system releasing vasopressin (AVP) and oxytocin (OXT), two neuropeptides hormones synthesized by the magnocellular neurons of the hypothalamus. Specific patterns of action potentials originating from cellular bodies of magnocellular neurons control the release of AVP and OT, but intra-neurohypophysis regulations do modulate the neuropeptides release. There is now good evidence for the effects of extracellular purines in the control of neurohypophysial secretion. This paper brings together evidence for the multiple, intricate actions of purines in the extracellular space of the neurohypophysis. It covers four main points. First, the activity-dependent release of endogenous ATP in the neurohypophysis. Second, the action of ATP on both neuronal and non-neuronal compartments of the neural lobe. Third, the termination of ATP positive feedback by ecto-nucleotidases. And finally the possible involvement of adenosine in the regulation of neurohypophysial secretion and glial plasticity. The data suggest that ATP and adenosine are physiological modulators of the release of neurohypophysial peptides by acting directly on nerve terminals and indirectly on neurohypophysial astrocytes. Since purinergic receptors are widespread in nervous and endocrine systems, the neurohypophysis appears as an useful model for studying the role of purines in the regulation of stimulus-secretion coupling and neuron-glia interactions. The feedback mechanisms found in the neurohypophysis could be ubiquitous, occurring throughout the central nervous system and in other secretory systems....

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Congresses 2002; 23(Suppl 2): 4-104 PubMed PMID: 12163856 Citation  Keywords:  Animals, Endocrine System:physiology, Humans, Light:adverse effects, Neoplasms:etiology,.   

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Congresses 2002; 23(Suppl 2): 84-87 PubMed PMID: 12163855 Citation  Keywords:  Animals, Humans, Light:adverse effects, Neoplasms:epidemiology, Neurosecretory Systems:physiology, Risk Factors,.   

: The International Symposium "Light, Endocrine Systems and Cancer" was held on May 2-3 at Cologne University, Germany. The symposium was organized by Professor Claus Piekarski and Dr. Thomas C. Erren, Institute and Polyclinic for Occupational and Social Medicine. The main goal of the symposium was to evaluate the epidemiological and experimental data on the effect of the exposure to light-at-night on cancer risk and to indicate the main directions of future research in the field. The symposium covered also the mechanisms and epidemiology of skin cancer which, however, are not included in the present summary....

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Editorial 2002; 23(Suppl 2): 79-81 PubMed PMID: 12163853 Citation  Keywords:  Animals, Humans, Light:adverse effects, Neoplasms:epidemiology, Neurosecretory Systems:physiology, Risk Factors,.   

: A conference was held at the University of Cologne on May 2-3, 2002, to discuss the strength-of-the-evidence supporting a linkage between light, endocrine systems and cancer. This overview of the conference is intended to summarize some of the key elements of the conference and to indicate both conclusions and research gaps identified by this reviewer....

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Journal Article 2002; 23(Suppl 2): 52-56 PubMed PMID: 12163849 Citation  Keywords:  Animals, Darkness, Humans, Light:adverse effects, Melatonin:physiology, Neoplasms:physiopathology, Photoperiod, Pineal Gland:physiology,.   

: Over the past few years, we have shown that the surge of melatonin in the circulation during darkness represents a potent oncostatic signal to tissue-isolated rat hepatoma 7288CTC, which is an ER+ adenocarcinoma of the liver. This oncostatic effect occurs via a melatonin receptor-mediated suppression of tumor cAMP production that leads to a suppression of the tumor uptake of linoleic acid (LA), an essential fatty acid with substantial oncogenic properties. The ability of LA to promote cancer progression is accomplished by its intracellular metabolism to 13-hydroxyoctadecadienoic acid (13-HODE) which amplifies the activity of the epidermal growth factor receptor/mitogen-activated protein kinase pathway leading to cell proliferation. By blocking tumor LA uptake, melatonin effectively blocks the production of 13-HODE and thus, markedly attenuates tumor growth. A similar effect of melatonin is observed in tissue-isolated, ER+ MCF-7 human breast cancer xenografts and nitrosomethylurea (NMU)-induced rat mammary cancers. When male rats bearing tissue-isolated hepatomas are exposed either to constant bright light (300 lux) or dim light (0.25 lux) during the dark phase of a 12L:12D photoperiod, the latency to onset was significantly reduced while the growth of tumors was markedly increased over a 4 wk period as compared with control tumors in 12L:12D-exposed rats. In constant light- and dim light during darkness-exposed rats, melatonin levels were completely suppressed while tumor growth, LA uptake and 13-HODE production were markedly increased. Similar results were obtained in constant bright light-exposed female rats bearing tissue-isolated NMU-induced mammary cancers or MCF-7 human breast cancer xenografts. To date, these studies provide the most definitive experimental evidence that light exposure during darkness increases the risk of cancer progression via elimination of the nocturnal melatonin signal and its suppression of tumor LA uptake and metabolism to 13-HODE....

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Journal Article 2002; 23(Suppl 2): 43-47 PubMed PMID: 12163847 Citation  Keywords:  Animals, Hormones:physiology, Humans, Models, Biological, Neoplasms:physiopathology, Neurosecretory Systems:physiology,.   

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....

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