Hypothalamo-Pituitary-Adrenal Gland Axis in Mice Inhaling Toluene Prior to Low-Level Long-Term Exposure to Formaldehyde

Abstract

ABSTRACT. 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.

Pituitary Remodeling Throughout Life: Are Resident Stem Cells Involved?

“…Another study also showed an expansion of cells expressing Pomc mRNA (as analyzed by in situ hybridization) 2-3 h after applying a cold stressor in rats (84). Exposure to chemical stressors (such as formaldehyde) also results in a rise of ACTH + cell proportion as analyzed in mice (85). Following exposure of rats to increased ambient temperature, ACTH + cells show reduced volume density, likely due to elevated secretion of ACTH from the corticotrope cells, which is concordant with the higher levels of ACTH (and corticosterone) found in the circulation (86).…”

Indoor Volatile Organic Compounds and Chemical Sensitivity Reactions

“…The toluene inhalation experiment consisted of two related studies. To mimic the preinhalation trigger produced by high-dose toluene, mice were exposed to 500 ppm toluene for three consecutive days prior to FA inhalation [32]. After the three days, groups of mice were exposed to various doses of (0, 80, 400, and 2000 ppb) FA as before [33].…”

Thymocytes are activated by toluene inhalation through the transcription factors NF‐κB, STAT5 and NF‐AT

“…As toluene is so widely used, the risk of being exposed to it continues to increase both indoors and outdoors (Arlien‐Soborg et al ., 1992). The central nervous system (CNS) has been characterized as the primary target of toluene, in cases of both acute and chronic exposure (Ahmed et al ., 2007; Sari et al ., 2005; Win‐Shwe et al ., 2007); however, there are few reports on the influence of toluene on naive cells in the immune system.…”