title: Effect of prolonged exposure to low concentrations of formaldehyde on the corticotropin releasing hormone neurons in the hypothalamus and adrenocorticotropic hormone cells in the pituitary gland in female mice.
abstract: We examine the effect on the hypothalamus-pituitary-adrenal gland (HPA) axis of prolonged exposure to low levels of formaldehyde in female C3H/He mice, using immunocytochemical and RT-PCR methods. Two groups of female mice were exposed to differing concentrations (0, 80, 400, 2000 ppb) of formaldehyde inhalation for 16 h/day, 5 days/week, for 12 weeks. The corticotropin releasing hormone (CRH)-immunoreactive (ir) neurons in the hypothalamus were then examined, together with the adrenocorticotropin hormone (ACTH)-ir cells and ACTH mRNA in the pituitary. One group comprised sham control mice. The other group was made allergic by injection of ovalbumin (OVA) and alum prior to exposure to formaldehyde, since most sick building syndrome (SBS) sufferers are women with allergic disease. These animals were further exposed to aerosolized OVA as a booster four times during the exposure period. Our results showed a dose-dependent increase in the number of CRH-ir neurons in the non-allergy (NAG) group. A similar pattern was found in ACTH-ir cells and ACTH mRNA. The allergy (AG) model group showed an increase in basal levels of all markers of HPA activity. Moreover, the AG mice appeared to respond to the lowest concentration of formaldehyde, and all indices of HPA activity were reduced at the highest concentrations of formaldehyde. These results relate to an important clinical issue and also have implications in the broader area of HPA regulation. We conclude that our experimental system may be a suitable animal model for SBS and/or multiple chemical sensitivity (MCS).
authors.affiliation: Laboratory of Veterinary Anatomy, Graduate School of Agriculture and Biological Sciences, Osaka Prefecture University, Gakuen-cho 1-1, Sakai, Osaka, 599-8531 Japan.
authors.forename: Dwi Kesuma
authors.initials: DK
authors.lastname: Sari
authors.forename: Sachi
authors.initials: S
authors.lastname: Kuwahara
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Tsukamoto
authors.forename: Hajime
authors.initials: H
authors.lastname: Hori
authors.forename: Naoki
authors.initials: N
authors.lastname: Kunugita
authors.forename: Keiichi
authors.initials: K
authors.lastname: Arashidani
authors.forename: Hidekazu
authors.initials: H
authors.lastname: Fujimaki
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Sasaki
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000096:biosynthesis*; D000818:Animals; D003346:Corticotropin-Releasing Hormone / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004781:Environmental Exposure; D005260:Female; D005557:Formaldehyde / Q000008:administration & dosage*; D007031:Hypothalamus / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010047:Ovalbumin / Q000633:toxicity; D010903:Pituitary Gland, Anterior / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism
chemical_list: D005557:Formaldehyde; D000324:Adrenocorticotropic Hormone; D010047:Ovalbumin; D003346:Corticotropin-Releasing Hormone