Developmentally-induced Hypothyroidism Alters mRNA Expression of Cerebral Angiotensin II Type 1 and Type 2 Receptors of Offspring in a Mouse Model

The impact of hypothyroidism on cerebral renin-angiotensin system (RAS) remains poorly understood. This study was aimed to examine the impact of methimazole (MMI)-induced hypothyroidism on mRNA expression of angiotensin 11 type 1 receptor-a (AT1a) and type 2 (AT2) receptors in the mouse brain. Pregnant C57BL/6J mice in hypothyroid (H) group received an administration of 0.03% MMI in the drinking water from gestational day 10, and at postnatal day (P) 7, these dams were divided into two subgroups: perinatal hypothyroid (H1) and permanent hypothyroid (H2) groups. Dams in the HI group stopped receiving MM1, and their litters received pure water after weaning (P21). Dams in the H2 group continued to receive MMI treatment until weaning, and their litters received MMI treatment until sacrifice. The relative expressions of cerebral AT1a and AT2 mRNA were determined by quantitative real-time polymerase chain reaction (PCR). In the H I group, the cerebral AT1a mRNA expression of offspring was significantly decreased during their first two postnatal weeks. and recovered to normal level thereafter. However, cerebral AT1a mRNA expression of H2 group was reduced persistently during postnatal development. Conversely, cerebral AT2 mRNA expression in the 112 group was significantly increased compared with the controls at P14 and P21. In conclusion, we found that developmentally-induced hypothyroidism may alter mRNA expression of cerebral AT1a and AT2 in the mouse offspring.