Behavioral development in adolescent rats of perinatal hypothyroidism and its relations to androgen receptor gene expression in hippocampus

Abstract

To investigate the behavioral development in adolescent rats of perinatal hypothyroidism and its relation to androgen receptor (AR) gene expression in the hippocampus. Perinatal hypothyroidism was induced by gavages 50 mg/d of propylthiouracil solution in 48 dams starting at embryonic day 15 through the lactation period. Twenty-four pups (M:F=1) of perinatal hypothyroidism were injected intraperitoneally with 2 microg T(4)/100 g BW daily from the day of birth to the age of 21 days (treatment group); 24 pups (M:F=1) without treatment were designated as hypothyroidism group. And 24 normal pups (M:F=1) served as the control group. The effects of perinatal hypothyroidism on the abilities to learn and retain memory traces and on behavior were observed in rats of both sexes at 60 days. Experiments were performed using models of conditioned "open" field test and passive avoidance reflexes. Hippocampus samples were collected and AR mRNA was detected by competitive RT-PCR. Perinatal hypothyroidism caused an increase of crossing number and decrease of rearing and defecation in both sexes. In treatment groups, only the crossing number in male didn't reach the normal level (P >0.05). In passive avoidance test, hypothyroidism groups showed more mistakes in both sexes and shorter latencies in males, the females performed better than males (P <0.01). The treatment groups performed significantly better than the age-matched hypothyroidism groups and reached the normal level (P >0.05). AR mRNA levels in hippocampus of hypothyroid group were lower than those of the controls in males, and the levels in treatment groups were significantly higher in comparison with the hypothyroidism groups (P <0.01). There were no significant differences among the three female groups (P >0.05). In male group, there was negative correlation between the number of crossing and AR mRNA in the hippocampus (r=-0.537, P=0.001), negative correlation between the number of mistake and AR mRNA (r=-0.532, P=0.001), and positive correlation between the latency and AR mRNA (r=0.564, P=0.000). Perinatal hypothyroidism results in hyperactivity and anti-anxiety effects on adolescent rats, the sex difference is depleted, and also causes learning and memory impairment but the degree of influence higher in male than female. The decreased level of AR mRNA expression in hippocampus contributes to the change of behavioral ability in adolescent male.