Nongenomic activation of phosphatidylinositol 3-kinase by thyroid hormone

Purpose of review A nongenomic action that does not directly and initially influence gene expression but rather causes a rapid effect such as activation of signaling cascades, has been recently described. The involvement of a thyroid hormone receptor, however, is not clear. In this review, we focus on the recent advances made in our understanding of the mechanism concerning a thyroid hormone receptor-mediated nongenomic action of thyroid hormone. Recent findings It was recently reported that thyroid hormone induces the activation of phosphatidylinositol 3OH-kinase which generates phosphatidylinositol 3,4,5-triphosphate, leading to the activation of the downstream signaling molecules such as protein kinase B. This nongenomic action of thyroid hormone requires binding with the thyroid hormone receptor. Moreover, the interaction between the thyroid hormone receptor and the regulatory subunit of phosphatidylinositol 3OH-kinase, p85α, was demonstrated in human skin fibroblasts, thyroid tissue extracts and a rat pituitary cell line GH4C1. Summary The phosphatidylinositol 3OH-kinase pathway plays critical roles in cell survival and differentiation through regulating enormous downstream molecules. Understanding of the thyroid hormone action on this pathway will provide a new insight into the physiological and pathological roles played by thyroid hormone.