Endocrine Abstracts

Thyroid hormone (TH) plays an important role for brain development. As the fetal thyroid gland only starts providing hormone at the end of pregnancy, the developing brain crucially depends on maternal thyroid hormone in early developmental periods. In previous studies, we have observed that in particular the central control of cardiovascular functions critically depends on maternal thyroid hormone for proper development; however, the precise window when the hormone is beneficial has remained to be determined. To address this question, we used mice expressing a mutant thyroid hormone receptor α1 (TRα1 + m), which exhibits a reduced sensitivity to the hormone. Under physiological conditions, this leads to a receptor-mediated hypothyroid phenotype; however, the receptor can be reactivated during any given time period by raising the circulating thyroid hormone levels pharmacologically. For this study, we mated male TRα1m mice with wildtype females and treated these dams either in the first or the second half of pregnancy with thyroid hormone. We then compared the resulting TRα1 + m offspring, in which TRα1 signaling had be reactivated during these developmental windows, with the resulting wildtype mice that were overexposed as embryos to thyroid hormonespecifically in these periods and untreated control offspring of both genders. In our study, we found a significant decrease of heart weight in male TRα1 + m independent of the treatment, suggesting that this phenotype is an acute and not a developmental action of the mutant TRα1. Most remarkably, we found a significant increase in heart rate in the wildtype male offspring that were exposed in the second half of the pregnancy to elevated thyroid hormone, underlining our previous findings that this period is absolutely crucial for the establishment of the central control of cardiovascular functions. Taken together our findings demonstrate that maternal thyroid hormone is of particular relevance for establishing the cardiovascular set points during the second half of pregnancy. The data therefore further advocate current initiatives to routinely monitor thyroid hormone levels during pregnancy to avoid adverse health effects in the offspring.