Interactive Effects of Exercise, Sex Hormones, and Transient Congenital Hypothyroidism on Long-Term Potentiation in Hippocampal Slices of Rat Offspring

Introduction: The long-term adverse effects of transient thyroid function abnormalities at birth on intellectual development are proven. The effect of exercise increases in the presence of sex hormones. The current study aimed at investigating the possibility that a combination of sex hormones and exercise has synergistic effects on neural plasticity in Transient Congenital Hypothyroidism (TCH) rats. Methods: To induce hypothyroidism in the mothers, Propylthiouracil (PTU) was added to drinking water (100 mg/L) on the 6th day of gestation and continued until the 21st Postnatal Day. From Postnatal Day (PND) 28 to 47, the female and male pups received 17 beta-estradiol and testosterone, respectively. The mild treadmill exercise began 30 minutes after the sex hormones or vehicle administration. On PND 48, electrophysiological experiments were performed on brain slices. Results: Increase of Long-Term Potentiation (LTP) was observed in sedentary-non-hormone female rats of TCH group, compared with that of the control. The exercise enhanced LTP in control rats, but the hormones showed no significant effect. The effect of exercise and sex hormone was not significant in the TCH group. The combination of exercise and testosterone enhanced LTP in TCH male rats, while the combination of exercise and estradiol or each of them individually did not produce such an effect on LTP in TCH female rats. Conclusion The study findings showed an increase in excitatory transmission despite the returning of thyroid hormone levels to normal range in TCH female rats. Also a combination treatment including exercise and testosterone enhanced LTP in male rats of TCH group, which was a gender-specific event.