The Thyroid Gland

Felix E. Grissom, Ph.D

2219 Adams Bldg

Howard University

Tel. 202 806-4512

Thyroid Gland: Hormones and Iodine Metabolism

• C-cells – calcitonin (covered later)

• Follicule cells– Amine hormones:

– thyroxine, T1, T2 & T3

growth metabolism

• Thermogenic

Thyroid Gland: Hormones and Iodine Metabolism

Figure 23-7b: The thyroid gland

Thyroxine and its precursors: Structure & Synthesis

Figure 23-8: Thyroid hormones are made from tyrosine and iodine

Thyroxine and its precursors: Structure & Synthesis

Figure 23-9: Thyroid hormone synthesis

Thyroid Hormone:Transport

• T3 & T4 leave the thyroid gland by diffusion

• Both are transported in blood by three transport proteins, Thyroxine binding globulin (TBG), transthyretin and albumin

• A majority (70%) of T4 & T3 is bound to TBG

• Both enter their target cells by diffusion

Thyroxine and its precursors: Activity

• T4 mainly functions as a prohormone. T3 is the main active thyroid hormone and has the highest binding affinity for thyroid hormone receptor (TR).

• Thyroid hormone activity can be increased in plasma without new synthesis by converting T4 to T3.

• If too much thyroid activity is present T4 is converted to the inactive metabolite rT3 to reduce activity.

Thyroxine and its precursors: Activity

Regulation of thyroid Gland Activity

• Thyroid hormone feedback regulation of gland activity via suppression of TRH and TSH secretion

• Autoregulation of thyroid gland activity via the Wolfc-Chaikoff Effect

• Energy intake and adipose tissue stores regulation of thyroid gland activity via leptin and CNS regulation of TRH secretion

Thyroid Hormone Feedback Regulation

• Hypothalamic TRH stimulates pituitary thyrotrope cells to release thyroid stimulating hormone (TSH).

• TSH stimulates thyroid epithelial cells to release T3 and T4.

• T3 (mainly) stimulates a multitude of cell types resulting in the activities exhibited

• T4 & T3 feedback to inhibit pituitary & hypothalamic secretion of TSH and TRH

Regulation by Energy Intake/Adipose Stores

T3 & T4 Control Pathways & Diseases from Malfunction

• Hypothalamus

• Anterior Pituitary

• Thyroid

• Hypothyroidism

• Goiter (TSH )

• Grave's disease

T3 & T4 Control Pathways & Diseases from Malfunction

Figure 23-12: Thyroid hormone pathway

T3 & T4 Control Pathways & Diseases from Malfunction

Thyroid Gland Summary I• The thyroid gland is the source of tetraiodothyronine T4 and

triiodothyronine (T3). The basic unit of the thyroid gland is the follicle which consists of a single layer of epithelial cells surrounding a centrial lumen that contains colloid or stored hormone.

• T4 and T3 are synthesized from tyrosine and iodide by the enzyme peroxidase. Tyrosine is incorporated in peptide linkage within the protein thyroglobulin. After iodination, two iodotyrosine molecules are coupled to yield iodothyronines.

• Secretion of stored T4 & T3 requires retrieval of thyroglobulin from the follicle lumen by endocytosis. To support hormone synthesis, Iodine is actively concentrated by the gland and conserved within it by recycling the iodotyrosine molecules that escape coupling within the thyroglobulin.

• Thyrotropin (TSH) acts on the thyroid gland via its plasma membrane

receptor and cAMP to stimulate all steps in the production of T4 & T3. These steps include iodide uptake, iodination and coupling, and retrieval from thyroglobulin. TSH also stimulates glucose oxidation, protein synthesis, and growth of the thyroid epithelial cells. This last effect is partly mediated by insulin-like Growth factors.

Thyroid Gland Summary II• More than 99.5% of the T4 and T3 circulate bound to the protein thyroglobulin

(TBG), transthyretin, and albumin. Only the free fraction of T4 & T3 are biologically active. Changes in in TBG levels require corresponding changes in in thyroid hormone secretion to maintain normal concentrations of free T4 & T3.

• T4 functions largely as a prohormone. Monodeiodination of the outer ring yields 75% of the daily production of T3, which is the principle active hormone. Alternatively, monodeiodination of the inner ring yields reverse T3 (rT3), which is biologically inactive. Proportioning of T4 between T3 & rT3 regulates the availability of active hormone.

• T3 and, to a much lesser extent, T4 bind to a thyroid hormone receptor (TR) that itself exists linked to thyroid regulatory elements (TREs) in target DNA molecules. Activation results in expression or suppression of the expression of a large number of enzymes. As well as structural and other functional proteins.

• Thyroid hormone increases and is a major regulator of basal metabolic the rate. Oxygen utilization is increased by a mechanisms that include increases in in the size and number of mitochondria, Na,K-ATPase activity, and the rates of glucose and fatty acid oxidation and synthesis

Thyroid Gland Summary III• Additional important actions of thyroid hormone are to increase heart rate,

cardiac output, and ventilation and to decrease peripheral resistance. These actions require the the increased tissue oxygen demand. The corresponding increase in heat production leads to increased sweating. Substrate mobilization and disposal of metabolic products are enhanced.

• Other thyroid hormone effects on the central central nervous system and skeleton are crucial for normal growth and development. With children. in the absence the hormone, brain development is retarded and cretinism results. The stature shortens and the bones fail to mature. With adults, thyroid hormone increases the rate of bone resorption and the rates of skin and hair degradation.

• Hyperthyroidism and hypothyroidism are usually easily diagnosed. Both are very amenable to therapy.