Study of neurogenic involvement in arginine-vasopressin and oxytocin release under basal and environmentally stimulated conditions

The arginine-vasopressin (AVP)-ergic and oxytocin (OXT)-ergic neuroendocrine systems have multiple functions in homeostatic maintenance. Their (co)existence, the interactions between them and the regulatory elements involved, e.g. the neurogenic systems related to monoamines such as serotonin (5-HT), norepinephrine (NE) or epinephrine (E) or the neuropeptide galanin (GAL) are at the center of scientific interest and have been partially described to date. However, these studies are related mainly to the higher levels of release located in either intrahypothalamic or other central nervous superior areas, and only slightly to the neurohypophysis (NH), which could also be a site of AVP and OXT expression. We have estabished that primary NH cultures may be used to study the release of AVP and OXT, and our group has already partially identified the involvement of some neurogenic monoamine regulators. We set out to acquire a more profound understanding of the roles of a wider range of neurogenic systems, under basal and stimulated conditions at the level of NH. We therefore attempted to elucidate the roles of NE and E and to identify the acting receptors. We set out to reveal the interactions between GAL and the monoamines of interest in AVP and OXT release. To attain these aims, we performed incubation procedures with related receptor agonists and/or antagonists on cultured pituicytes. If the secreted amounts of AVP and OXT are modulated, physiological or behavioral disturbances may appear. Homeostasis can be implemented by behavior including the largely AVP- and OXT-mediated anxiety and aggression. Independently or in interaction with neurogens and/or others, and incidentally influenced by internal-external stimuli, AVP and OXT are involved in a broad range of behavioral traits. Various external impacts affect hormonal release at different regulatory levels in the brain. Nevertheless, besides chemization, we should increasingly calculate with the relevance of ambient endocrine disruptor substances as possible external-environmental stimuli which may be capable of disturbing behavior and the underlying AVP and OXT mechanisms. We have therefore examined the consequences of a chosen environmental stimulus on anxiety and aggression and on AVP and OXT release in vivo and in vitro. We wished to know, how this stimulus can disturb the release, and how the changes can be interpreted in terms of a NH model. To provoke the stimulated condition, adult male rats were exposed to chlorobenzenes for 30, 60 or 90 days, after which AVP- and OXT-mediated behavior was examined in open-field, elevated plus maze and resident-intruder tests. NH cultures were prepared from the rats, and further incubation procedures with some relevant neurogenic regulators (5-HT and NE) were performed to study the release in vitro. The AVP and OXT levels of NH supernatants and the AVP, OXT and adrenocorticotrophic hormone (ACTH) levels of the blood were measured with immunologic methods. Similarly to the monoamines examined earlier, NE and E increased the AVP and OXT release in NH cultures in vitro. We concluded that α1-receptors are involved in E-stimulated AVP and OXT release, and β2-receptors in NE-stimulated AVP and OXT release. GAL interacted with all the monoamines, decreasing or inhibiting their effects enhancing AVP and OXT release. The plasma AVP, OXT and ACTH levels were increased, to extents depending on the duration and dose of the exposure. The 5-HT- and NE-stimulated release of AVP and OXT in our NH model was disturbed following the external impact. Several anxiety-related and aggressive behavioral elements were also enhanced following exposure, while certain explorative and locomotive elements of the animals were decreased. As both physiological and behavioral elements were modulated by chronic, subtoxic doses of chlorobenzenes, it was concluded that low doses of such environmental endocrine disruptors may pose potential risks of anxiogenic and/or aggressive consequences in exposed subjects