Regulation of Thyroid Function by Retinol Saturase

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Thyroid hormones are major regulators of growth, cell differentiation, and energy homeostasis. These hormones are synthesized in follicular epithelial cells of the thyroid gland and secreted into the blood. Upon the uptake into tissues, locally expressed deiodinases then fine-tune thyroid hormone action in a cell type-specific manner. We found that the enzyme Retinol Saturase (RetSat), a NAD(P)H or FADH-dependent oxidoreductase initially shown to reduce retinol to 13,14-dihydroretinol that may also catalyze other reactions, is strongly expressed in murine and human thyroid gland. Moreover, RetSat expression in the murine thyroid was altered by iodide feeding, a known modulator of thyroid function. To dissect the function of RetSat in the thyroid, we generated a new genetic mouse model that deletes RetSat specifically in thyrocytes. Preliminary data gained from these mice implicate RetSat in the synthesis of thyroid hormones. Hence, this proposal aims at investigating the underlying mechanisms, characterize the phenotypical consequences, and elucidate RetSat’s role in hypo-and hyperthyroid states. Addressing these question will decipher the function of RetSat in the thyroid gland and may identify a novel pharmacologic target to treat thyroid dysfunction and related metabolic pathologies.