The effects of intracerebroventricularly administered apelin-13 on hypothalamus-hypophysis-thyroid axis in rats

Apelin is a peptide hormone called as the ligand for the G protein-coupled APJ receptor. Apelins and their receptors are expressed in the central nervous system, including the hypothalamus and numerous other peripheral tissues. Since APJ is expressed particularly intense in the hypothalamus and thyroid gland, Apelin is thought to play many roles on hypothalamus-pituitary-thyroid axis and energy metabolism. The present study was designed to investigate the effects of chronic intracerebroventricular (icv) administration of two different doses of apelin-13 on hypothalamus-hypophysis-thyroid axis and energy metabolism. In this study, fourty Sprague Dawley male rats were used, and were divided randomly into 4 groups (n=10 in each). No operation was applied to the rats in the control group. Rats in the experimental groups, apelin-13 at 1 and 10 nmol doses, and rats in sham group, the same amount of artificial cerebrospinal fluid was injected icv for seven days (10 µl/h). After seven days, animals were decapitated and their brain, blood, white and brown adipose tissues were taken. TRH mRNA levels in hypothalamus, uncoupling protein 1 (UCP1) mRNA levels in white and brown adipose tissues, UCP3 mRNA levels in muscle tissue of the groups were determined by RT-PCR method. Serum T3 and T4 levels were measured by using ELISA method. The levels of hypothalamic TRH mRNA were not different between the groups. While serum TSH levels significantly increased compared to control group (p<0.05, p<0.01) levels, no difference was observed between sham and apelin groups. Serum T3 and T4 levels were significantly lower in sham and apelin treated groups compared with the control group (p<0.05, p<0.01 ve p<0.001). According to the sham group, only high dose apelin-13 administration was significantly decreased in serum T3 and T4 levels. Apelin-13 administration dose-dependently reduced UCP1 mRNA expression in white and brown adipose tissue and UCP3 mRNA expression in muscle tissue. Our results showed that the infusion of high doses of apelin-13 caused decreases serum T3 and T4 levels in the rats. In addition to, the UCP3 mRNA levels in the muscle tissue and UCP1 mRNA levels in the adipose tissues were significantly decreased by both doses of apelin-13. These results suggested that apelin-13 caused a decrease of energy expenditure by partially inhibiting hypothalamus-hypophysis-thyroid axis.