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Although measurements of blood triiodothyronine (T3), thyroxine (T4), and thyroid‐stimulating hormone (TSH) levels in rodent toxicity studies are useful for detection of antithyroid substances, assays for these measurements are expensive and can show high variability depending on blood sampling conditions. To develop more efficient methods for detecting thyroid disruptors, we compared histopathological and immunohistochemical findings in the thyroid and pituitary glands with blood hormone levels. Six‐week‐old male and female Sprague–Dawley rats (five rats per group) were treated with multiple doses of the thyroid peroxidase inhibitors propylthiouracil (PTU) and methimazole by gavage for 28 days. Significant decreases in serum T3 and T4 and increases in TSH were observed in the ≥1 mg/kg PTU and ≥3 mg/kg methimazole groups. An increase in TSH was also detected in male rats in the 0.3 mg/kg PTU group. Histopathological and immunohistochemical analyses revealed that follicular cell hypertrophy and decreased T4 and T3 expressions in the thyroid gland were induced at doses lower than doses at which significant changes in serum hormone levels were observed, suggesting that these findings may be more sensitive than blood hormone levels. Significant increases in thyroid weights, Ki67‐positive thyroid follicular cell counts, and TSH‐positive areas in the pituitary gland were detected at doses comparable with those at which changes in serum T4 and TSH levels were observed, indicating that these parameters may also be useful for evaluation of antithyroid effects. Combining these parameters may be effective for detecting antithyroid substances without relying on hormone measurements. In rats treated with PTU and MMI for 28 days, histopathological and immunohistochemical findings and serum hormone levels were compared to establish a simplified method for detecting antithyroid chemicals. The results demonstrated that histopathological analysis and T4 immunostaining in the thyroid gland were more sensitive parameters than blood hormone levels and that immunohistochemistry for thyroid Ki67 and pituitary TSH may also be useful for evaluation. [ABSTRACT FROM AUTHOR]

The aryl hydrocarbon receptor (AhR) is a ligand‐dependent transcription factor that binds to various environmental chemicals and contributes to numerous toxicological effects. However, the direct effects of AhR on the development of allergic diseases are not fully understood. The main aim of this study was to elucidate the action of AhR in the development of cutaneous allergies. Initially, the potential for a direct relationship between AhR and the immune cells was investigated in vitro, using murine bone marrow‐derived dendritic cells, human epidermal keratinocytes, and the mixed leukocyte reaction assay. Benzo[a]pyrene (BaP) and 6‐formylindolo[3,2‐b]carbazole were used as selective ligands for the AhR. Pretreatment with BaP and/or 6‐formylindolo[3,2‐b]carbazole significantly induced cytokine release by activated keratinocytes and T‐cell proliferation, whereas interleukin‐12 production in bone marrow‐derived dendritic cells was reduced by AhR activation. To confirm the in vitro results, in vivo experiments were also performed in T‐helper (Th)2‐type hapten toluene‐2,4‐diisocyanate‐ and Th1‐type hapten dinitrochlorobenzene‐induced mouse models of allergic dermatitis. Mice were orally administered BaP at 48, 24 and 4 hours before the final allergen challenge. In the Th2 model, ear‐swelling response and scratching behavior were promoted by BaP exposure, which supported the observed significant increases in local cytokine secretion. The infiltration of helper T cells, B cells and dendritic cells into the auricular lymph node was significantly enhanced by BaP administration, although Th1‐type immune responses were not influenced by AhR activation. Our findings demonstrate that AhR activation directly activates keratinocytes and T cells, which leads to the exacerbation of Th2‐type cutaneous allergy. To examine the direct action of aryl hydrocarbon receptor (AhR) in the development of cutaneous allergies, selective ligands for AhR were applied in vitro assays and mouse models of allergic dermatitis. Pretreatment with AhR ligands significantly induced cytokine release by keratinocytes and T‐cell proliferation. In the T‐helper 2‐type mouse model, both inflammatory and pruritic responses were promoted by AhR activation. Our findings demonstrate that AhR activation directly leads to the exacerbation of T‐helper 2‐type cutaneous allergy. [ABSTRACT FROM AUTHOR]