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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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Journal Article 2002; 23(Suppl 2): 37-42 PubMed PMID: 12163846 Citation  Keywords:  Aging:metabolism, Animals, Estrogen Replacement Therapy, Estrogens, Non-Steroidal:therapeutic use, Female, Homeostasis:physiology, Humans, Isoflavones, Menopause:physiology, Neurosecretory Systems:metabolism, Phytoestrogens, Plant Preparations, Receptors,.   

: Endocrine modulation by natural and synthetic chemicals and the eventually resulting beneficial or adverse effects for human and animal health are controversially debated not only among scientists but particularly in the public. Most information is available on so-called environmental estrogens, however the amount of information on substances interfering with other hormonal axes steadily increases, particularly on those exhibiting (anti)androgenic activities. The aim of this paper is to summarize existing data and to give an overview on the potential pathways leading to interferences of environmental hormones with homeostasis and eventually resulting health effects. Experimental evidence suggests the hypothesis that fetal and neonatal organisms may be at risk if exposed to environmental estrogens. In contrary, it appears as if phytoestrogens, particularly those with selective estrogen receptor modulator- (SERM-)like activities have the potential to be useful in medical application, both as dietary means and as pharmaceuticals. Lacking valid information about the detailed analysis of the molecular mode of action for environmental estrogens, the possibility for an ultimate classification of environmental estrogens in "dangerous endocrine disruptors" and phytoestrogens in "useful pharmaceuticals" cannot be supported conclusively. Nevertheless both activities are likely....

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Journal Article 2002; 23(Suppl 2): 28-36 PubMed PMID: 12163845 Citation  Keywords:  Animals, Humans, Light:adverse effects, Melatonin:physiology, Neoplasms:etiology, Photoperiod, Pineal Gland:physiology,.   

: The role of the modulation of the pineal gland function in development of cancer is discussed in the review. An inhibition of the pineal function with pinealectomy or with the exposure to the constant light regimen stimulates mammary carcinogenesis, whereas the light deprivation inhibits the carcinogenesis. Epidemiological observations on increased risk of breast cancer in night shift workers, flight attendants, radio and telegraph operators and on decreased risk in blind women are in accordance with the results of experiments in rodents. Treatment with pineal indole hormone melatonin inhibits carcinogenesis in pinealectomized rats or animals kept at the standard light/dark regimen (LD) or at the constant illumination (LL) regimen....

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Journal Article 2002; 23(Suppl 2): 23-27 PubMed PMID: 12163844 Citation  Keywords:  Animals, Biological Clocks:physiology, Humans, Light, Melatonin:physiology, Pineal Gland:physiology, Seasons,.   

: In mammals including man, the most important zeitgeber for endogenous rhythms is the environmental light/dark cycle. Mammals perceive light through the eyes and that perception is relayed to the suprachiasmatic nucleus (SCN) by means of neuronal signals. The SCN, in turn, innervates the pineal gland, resulting in the production and release of melatonin almost exclusively during night-time hours. Thus, besides object recognition, eyes serve as the sensory organ for detecting the presence or absence of light. The way that light entrains the SCN is still a matter of intense research. It has been shown, for example, that the light intensities required for affecting melatonin rhythms are much higher than the intensities needed for object identification. On the other hand, even in rodents who completely lack the "classical" photoreceptors of the retina, their endogenous rhythms still can be synchronized by normal light/dark cycles. These two observations led to the hypothesis that there must be photoreceptors, apart from the known (object-identifying) retinal photoreceptors, which are responsible for the entrainment of internal rhythms. Very recently, a number of reports showed that in fact a completely new type of retinal photoreceptor, located in ganglion cells, may be responsible for entraining the SCN. It contains a photopigment, melanopsin, which shares homologies with rhodopsin, but also is evolutionarily older. Compared to rods or cones, the melanopsin-containing neurons are rare, but evenly distributed within the retina, indicating that they serve as a global, integrating light sensor. These ganglion cells apparently project directly into the SCN. Taken together, these new developments in photo-chronobiology open new areas of research. It will be of special interest, for example, to determine how the photosensitive ganglion cells and their dendrites integrate the environmental light stimuli....

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Journal Article 2002; 23(Suppl 2): 17-22 PubMed PMID: 12163843 Citation  Keywords:  Breast Neoplasms:epidemiology, Circadian Rhythm:physiology, Female, Humans, Light, Melatonin:physiology, Photoreceptor Cells, Vertebrate:physiology, Risk Factors,.   

: The impact of breast cancer on women across the world has been extensive and severe. As prevalence of breast cancer is greatest in industrialized regions, exposure to light at night has been proposed as a potential risk factor. This theory is supported by the epidemiological observations of decreased breast cancer in blind women and increased breast cancer in women who do shift-work. In addition, human, animal and in vitro studies which have investigated the melatonin-cancer dynamic indicate an apparent relationship between light, melatonin and cancer, albeit complex. Recent developments in understanding melatonin regulation by light in humans are examined, with particular attention to factors that contribute to the sensitivity of the light-induced melatonin suppression response. Specifically, the role of spectral characteristics of light is addressed, and recent relevant action spectrum studies in humans and other mammalian species are discussed. Across five action spectra for circadian and other non-visual responses, a peak sensitivity between 446-484 nm was identified. Under highly controlled exposure circumstances, less than 1 lux of monochromatic light elicited a significant suppression of nocturnal melatonin. In view of the possible link between light exposure, melatonin suppression and cancer risk, it is important to continue to identify the basic related ocular physiology. Visual performance, rather than circadian function, has been the primary focus of architectural lighting systems. It is now necessary to reevaluate lighting strategies, with consideration of circadian influences, in an effort to maximize physiological homeostasis and health....

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Journal Article 2002; 23(Suppl 2): 14-16 PubMed PMID: 12163842 Citation  Keywords:  Humans, Light:adverse effects, Lighting, Physical Phenomena, Physics, Sunlight:adverse effects,.   

: The physical properties of light, both natural and artificial, play a significant role in its interaction with humans. Although there is a yet-to-be-explained duality between light as waves and light as photons, we do understand many of the characteristics of light that affect living things. Here I review the general history of light and its properties, especially those that affect human health....

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Journal Article 2002; 23(Suppl 2): 9-13 PubMed PMID: 12163841 Citation  Keywords:  Animals, DNA Damage, Humans, Light:adverse effects, Melatonin:metabolism, Neoplasms:etiology, Neurodegenerative Diseases:etiology,.   

: This brief review summarizes some of the biological effects of light exposure at an inappropriate time (during the normal dark period) and the potential negative physiological consequences of this light exposure. Two major systems are significantly influenced by light at night. Thus, the circadian system and melatonin synthesis are altered when light is extended into the normal dark period or when the dark period is interrupted by light. This summary reviews the potential sequelae of chronic inappropriate light exposure and the suppression of endogenous melatonin levels. Given that melatonin is a free radical scavenger and antioxidant, conditions that involve free radical damage may be aggravated by light suppression of melatonin levels. The conditions of particular interest for this review are excessive DNA damage (which potentially leads to cancer), cellular destruction in neurodegenerative diseases and aging itself. Further research should be conducted to more accurately define the potential negative impact of light at abnormal times on animal and human pathophysiology....

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Editorial 2002; 23(Suppl 2): 4-6 PubMed PMID: 12163840 Citation  Keywords:  Congresses as Topic, Humans, Neuroendocrinology:organization & administration, Societies, Medical,.   

: 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....

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