Negative Regulation of the Thyrotropin Gene by Thyroid Hormone

Thyroid hormone (T3 and T4) is secreted from the thyroid gland, and is known to reduce the level of serum thyrotropin (thyroid-stimulating hormone, TSH) in the pituitary gland (Sarapura et al., 2002; Shupnik et al., 1989) (Fig. 1A). This is a typical example of negative feedback between the pituitary and endocrine organs, and is a key component of thyroid hormone homeostasis. TSH is one of the peptide hormones generated in the anterior pituitary, and is a heterodimer composed of an ┙ chain (┙-glycoprotein subunit, ┙GSU) and a ┚ chain (TSH┚) (Shupnik et al., 1989). While ┙GSU is common to follicle stimulating hormone (FSH), luteinizing hormone (LH) and chorionic gonadotropin (CG), TSH┚ is specific to TSH alone. Although the concentration of serum T4 is much higher than that of T3, T4 is converted to T3 by deiodinase (Dio) in the TSH-producing cells (thyrotrophs) of the pituitary (Christoffolete et al., 2006), and T3 exhibits biological activity as a thyroid hormone (Gereben et al., 2008). T3 inhibits expression of both TSH┚ and ┙GSU at the transcriptional level (Shupnik et al., 1989). The magnitude of T3-induced repression of the TSH┚ gene is greater than that of ┙GSU. Here, we provide an overview of the molecular mechanisms involved in T3-induced negative regulation of the TSH┚ gene and its related genes.