We studied the change in the hypothalamo-pituitary-adrenal gland (HPA) axis upon adding prior
toluene inhalation to our previous
formaldehyde inhalation experiments to determine whether short term exposure to relatively high levels of
toluene triggers
multiple chemical sensitivity (MCS). Data come from immunocytochemical, morphometrical and RT-PCR measurements. Four groups of adult female mice were exposed to differing concentrations (0, 80, 400, and 2,000 ppb) of
formaldehyde for 16 hr/day, 5 days/week for twelve weeks, after the mice were exposed intranasally to 500 ppm
toluene per mouse for 6 hr/day, for 3 days. We found that the number of
corticotropin releasing hormone (CRH)-immunoreactive (ir) neurons was up-regulated according to the amount of
formaldehyde as well as inhalation of
formaldehyde alone in our previous experiment. The proportion of
adrenocorticotropin hormone (
ACTH)-ir cells increased according to the
formaldehyde concentration, though there was no significant difference between the 400 and 2,000 groups. The number of
ACTH-ir cells was higher in the 400 group than in the other groups (0, 80, and 2,000). Expression of
ACTH-
mRNA was also up-regulated according to the quantity of
formaldehyde. The sinusoid in the anterior pituitary showed more dilatation in the 400 and 2,000 groups than in the control group, especially in the 2,000 group. We propose that exposure to
toluene prior to inhalation of
formaldehyde has no effect on the HPA axis and as a trigger of MCS, although greater sinusoid dilatation was found in the anterior pituitary gland at higher concentrations of
formaldehyde.