Figure 1.
Thyroid hormone synthesis. The thyroid gland makes both T4 and T3, although T4 predominates. The hypothalamus senses low TH in the circulation and responds by stimulating synthesis and secretion of TRH (thyroid releasing hormone), which in turn circulates and stimulates synthesis and secretion of TSH (thyroid stimulating hormone) by the pituitary. Circulating TSH then increases T4 and T3 production by the thyroid and ultimately in the circulation. Tissue-specific deiodinases (“DIO”) are expressed in peripheral tissues such as brain astrocytes to increase local concentrations of T3 from circulating T4. However, we propose that T4 may also act directly on TRs to regulate gene transcription in neurons in the absence of deiodinase 2 conversion to T3.