Sustained pituitary T3 production explains the T4-mediated TSH feedback mechanism

Endocrinology. 2023 Oct 21:bqad155. doi: 10.1210/endocr/bqad155. Online ahead of print.ABSTRACTThe regulation of thyroid activity and thyroid hormone (TH) secretion is based on feedback mechanisms that involve the anterior pituitary thyrotropin (TSH) and medial basal hypothalamus (MBH) TSH-releasing hormone (TRH). Plasma T3 levels can be "sensed" directly by the anterior pituitary and MBH, plasma T4 levels require local conversion of T4 to T3, which is mediated by the type 2 deiodinase (D2). To study D2-mediated T4 to T3 conversion and T3 production in the anterior pituitary gland, we used mouse pituitary explants incubated with 125I-T4 for 48 h to measure T3 production at different concentrations of free T4. The results were compared to cultures of D1 or D2-expressing cells, as well as freshly isolated mouse tissue. These studies revealed a unique regulation of the D2 pathway in the anterior pituitary gland, distinct from that observed in non-pituitary tissues. In the anterior pituitary, increasing T4 levels reduced D2 activity slightly but caused a direct increase in T3 production. However, the same changes in T4 levels decreased T3 production in human HSkM cells and murine C2C12 cells (both skeletal muscle) and mouse bone marrow tissue, which reached zero at 50pM free T4. In contrast, the increase in T4 levels caused the pig kidney LLC-PK1 cells and kidney fragments to proportionally increase T3 production. These findings have important implications for both physiology and...
Source: Endocrinology - Category: Endocrinology Authors: Source Type: research