Thyroid Gland Function
Primary Hormones and Their Production
The thyroid gland produces two potent hormones—thyroxine (T4) and triiodothyronine (T3)—that regulate basal metabolic processes and oxygen consumption in nearly all body tissues. 1 The gland is a butterfly-shaped organ located in the front of the neck just above the trachea, weighing approximately 15-20 grams in adults. 1
Thyroid hormone production is primarily regulated by thyroid stimulating hormone (TSH) from the pituitary gland, which controls multiple aspects of thyroid hormone synthesis including stimulation of iodide uptake, activation of thyroid peroxidase enzyme, regulation of oxidation and organification of iodide, control of secretion of T4 and T3 into circulation, and influence on post-translational modifications of thyroglobulin. 2
TSH itself is regulated by thyrotropin-releasing hormone (TRH) from the hypothalamus, creating a feedback loop where thyroid hormones inhibit both TRH and TSH production at the transcriptional level. 3
Metabolic and Developmental Functions
Thyroid hormones influence basal metabolic processes by enhancing oxygen consumption in nearly all body tissues, making them crucial for energy homeostasis. 1, 4
The major target tissues for thyroid hormone action are the brain, liver, muscle, heart, and adipose tissue, where they regulate metabolism, growth, and cellular function. 4
Beyond metabolism, thyroid hormones influence linear growth, brain function (including intelligence and memory), neural development, dentition, and bone development. 1
Hormone Metabolism and Activation
Circulating T4 produced by the thyroid can be metabolized through several pathways: activation of thyroid hormone, deactivation of thyroid hormone, or excretion of thyroid hormone and subsequent metabolites. 5
The major classical pathways of thyroid hormone metabolism are deiodination, sulfation, glucuronidation, and ether-link cleavage, which determine local thyroid hormone levels and action at the tissue level. 5
Adequate iodine intake is essential for proper thyroid hormone synthesis, with daily requirements of 150 μg/day in adults, and iron and selenium are also crucial for proper thyroid function. 2
Cellular Mechanism of Action
Thyroid hormones exert their effects through thyroid hormone receptors (TRs) by controlling the expression of target genes, with transcriptional activity modulated by multiple factors including various TR isoforms, diverse thyroid hormone response elements, different heterodimeric partners, coregulators, and cellular location of TRs. 6
The thyroid hormone receptor ligand-dependent activation function (AF-2) domain plays an unanticipated role in thyroid hormone negative regulation of the hypothalamic-pituitary-thyroid axis. 3
Regulatory Feedback System
The hypothalamic-pituitary-thyroid axis operates through a complex mechanism where hypothalamic TRH stimulates TSH secretion from the anterior pituitary, TSH then initiates thyroid hormone synthesis and release from the thyroid gland, and thyroid hormones inhibit both TRH and TSH synthesis to maintain homeostasis. 3
Although opposing TRH and thyroid hormone inputs regulate this axis, transgenic animal studies revealed an unexpected, dominant role for TRH in regulating the hypothalamic-pituitary-thyroid axis, contrary to the previous belief that thyroid hormone negative feedback at the pituitary was the primary regulator. 3