New insights into morphological, stereological and functional studies of the adrenal gland under exposure to the potent goitrogen thiourea.

Abstract

Thiourea (thiophen-3-yl-acetic acid) is a well established antithyroid drug used for treating hyperactivity of the thyroid gland as it blocks the conversion of thyroxine (T4) to triiodothyronine (T3) in peripheral tissues. Human exposures to thiourea include contaminated drinking water and vegetables for its extensive use in fertilizers. Chronic thiourea exposure can cause thyroid dysfunction leading to redox imbalance. However, such effects on morphological, quantitative, functional and hypothalamo-pituitary-adrenocortical axis (HPA) analysis of the adrenal gland are yet to be explored. The aim was to explore the effect of thiourea on structural and functional status of the adrenocortical region with special reference to the HPA axis. Control rats were fed a normal laboratory standardized diet whereas to experimental rats, thiourea at a dose of 0.3 mg/day/Kg body weight was administered orally, once every day for consecutive 28 days. Histology and histometry, including morphometry of the adrenal, adrenal Δ5 3β HSD and 17β HSD activity, LPO level and serum corticosterone profile were assessed. Statistical significance was studied by ‘Mann-Whitney U’ test at p<0.05. Hypertrophy and hyperplasia of the adrenocortical cells was found especially in the layer zona fasciculata (p=0.0027) and enhanced adrenal Δ5 3β HSD activity (p=0.0067) in comparison to that of the control. Increased lipid peroxidation (p=0.0054) and up-regulated corticosterone release (p=0.0064) through adrenocortical stress signalling pathway were also noted. Stereological analysis of the left adrenal gland showed significant increase in volume (p=0.0025) and mass of cells (p=0.0031) in adrenocortical region in comparison to that of control animals. This study concludes that thiourea, in addition to its antithyroidal activity, develops stress in the adrenal as evident by enhanced lipid peroxidation in the gland that in turn through the HPA axis causes hypertrophy and hyperplasia of adrenocortical cells to enhance synthesis and release of corticosterone secretion to counteract the stress developed under the influence of this potent chemical agent.