Examination of endocrine disruptor effects in neuroendocrine systems, in vivo and in vitro

Abstract

The effects of environmental loads (physical, chemical, biological) interfere with human homeostatic psycho-neuroendocrine-immune mechanisms. Clarifying the role of the triggered effects and their impact factors became an acute task for the 21st century. The aim of the present study was to investigate the effects of chemical (aromatic/halogenated hydrocarbons) and physical (extreme low frequency and dose electromagnetic fields: ELF-EMF) environmental loads as endocrine disruptors (ED). In addition, we have investigated the role of these factors in cell and individual exposure to clarify the mechanisms induced. We considered it particularly important to study the relationship between indirect and direct effects in cell transformation events associated with endocrine regulatory disorders. In our work, we developed in vivo (Wistar rat chlorobenzene treatment through gastric tube; ♀ Wistar rats treatment by subcutaneous estrogen implantation; treatment of turkey with ELF-EMF), and in vitro (neurohypophysis, adenohypophysis monolayer cell culture) exposure models and standardized them for general viability and/or specific functional attractors (mechanism cycles). The chemical agents tested were hexachlorobenzene: 1,2,4-trichlorobenzene = 1:1 (mClB); 1,4-dichlorobenzene (dClB); phenuron (PU), monuron (MU) and diuron (DU) as ED investigated for dose and time dependence. It has been found that said agents have ED effects on OT, AVP, ACTH and PRL release. Furthermore, we have determined the human toxicity potential(HTP) values for dClB in the chemical exposures studied. We have demonstrated that ELF-EMF is a cellular ED which modifies the functions of cell membrane receptors (G proteins) involved in regulatory mechanisms. We developed an adenohypophyseal prolactinoma (PRLOMA) model by estrogen stimulation through a positive feed-back mechanism. We have experimentally demonstrated that the functional derangement of the PRLOMA-like adenohypophysis with ED agents often triggers a non-compensable event cascade when compared to normal cell function. Based on our in vitro results, we also investigated the role of ED effects in the background of thyroid cell transformation disorders diagnosed in medical practice. We found a correlation between ED exposures and anti-TG or anti-TPO-labeled thyroid malignant tumors, respectively. Our findings reveal that mClB, PU, MU, DU, and ELF-EMF can be regarded as ED. In addition, we have demonstrated that chronic endocrine regulatory disorders may induce cell transformation so that the target cells of which show different behavior in their regulation compared to healthy cells. We have found a relationship between the real thyroid cell transformations (malignant tumors), the presence of anti-TG/anti-TPO markers and ED in the medical histories of the patients.