Endocrine Abstracts

JOINT969

It has been experimentally demonstrated that exposure to endocrine disruptor chlorobenzenes (ClB) alter behaviour by increasing anxiety and aggression in male Wistar rats. Little is known about the effects of chlorobenzene on females, but research showing strong maternal aggression towards offspring is of particular interest. Our group aimed to investigate the background of this evidence by studying the effects of dietary route ClB exposure in animal models of neurotransmitter/hormone relapse. Our work was aimed to investigate noradrenergic and serotonergic coupled vasopressin (AVP) and oxytocin (OT) release induced by ClB exposures. In our experiments, we administered subtoxic doses of ClB mixtures (hexaClB +1,2,4-triClB=1:1, mixed chlorobenzenes: mClB) at doses of 0.1; 1.0; and 10.0 µg/bw.kg to Wistar ♀ rats in vivo via a stomach tube; 0, 30, 60, 90 days. Subtoxicity of the doses was confirmed by liver enzyme assays. AVP and OT, liver enzymes and other parameters required for assay were determined from blood samples taken according to experimental time windows. Primary monolayer cell cultures (NH) were prepared from neurohypophyseal sterile tissue samples at the end of the treatment periods. The AVP and OT separation kinetics of the resulting in vitro models were determined for mClB-treated and untreated NH cultures. We then followed the effects of adrenergic (norepinephrine: NE 10^-6M) and serotonergic (serotonin: 5HT 10^-6M) receptor activation on AVP and OT secretion. The results were expressed as mg protein content of the cultures. RIA procedures were used for hormone measurements. Protein contents were measured by the modified Lowry method. Serum toxicity enzymes were measured by enzyme kinetic assays. Our results showed that mClB enhanced AVP and OT clearance in relation to treatment doses and durations. Activation of NE and 5HT neurohypophyseal receptors significantly increased AVP and OT release. Since the role of these two neurotransmitters is dominant in aggression and anxiety, the strong behavioural disturbances induced by mClB in ♀ Wistar rats may be due to NE and 5HT mediated AVP and OT secretion.