Thyroid & Parathyroid TH affects virtually all systems of the body Acts as a modulator of a wide-variety of physiological processes Critical role in growth & development Nervous system depends on it Its presence seems to be required for normal functioning (modulates, not initiate) Deranged thyroid function is most prevalent endocrine disease (4-5% of USA).

Copyright © 2014 John Wiley & Sons, Inc. All rights reserved.

Copyright © 2014 John Wiley & Sons, Inc. All rights reserved. Thyroid Gland “Butterfly” gland - inferior to the larynx and anterior to the trachea. It has right and left lateral lobes connected by an isthmus. Some also have a pyramidal lobe projecting from the isthmus. Copyright © 2014 John Wiley & Sons, Inc. All rights reserved.

Copyright © 2014 John Wiley & Sons, Inc. All rights reserved. Thyroid Gland

Copyright © 2014 John Wiley & Sons, Inc. All rights reserved. Thyroid Hormones The thyroid synthesizes two hormones: thyroxine (T4) and triiodothyronine (T3) from the a.a. tyrosine. These two iodinated hormones have a diverse number of functions within and between members of the different vertebrates. These hormones are necessary for normal growth and development and without them somatic and mental growth are retarded. Copyright © 2014 John Wiley & Sons, Inc. All rights reserved.

Thyroid Follicles The functional units of the thyroid are the individual thyroid follicles These consist of a cuboidal epithelium arranged as a single layer surrounding a lumen that contains colloid material (thick gelatin material) Follicular cells synthesize a protein, called thyroglobulin, which is released into the colloidal space by vesicular exocytosis. Thyroglobulin is the substrate for tyrosine iodination and subsequent synthesis of thyroid hormones. In the mammal, so called clear cells, (C), are present within the follicular wall and the extracellular space between the follicles. C cells are the source of calcitonin, important for Ca homeostasis

Copyright © 2014 John Wiley & Sons, Inc. All rights reserved. Thyroid Follicles Follicular cells are stimulated by TSH to produce thyroid hormones: thyroxine (tetraiodothyronine, T4) Most abundant; Less potent triiodothyronine (T3) Less abundant; More potent Parafollicular cells produce: - calcitonin - helps regulate calcium homeostasis.

Release of TH Nervous Thyroid is richly supplied with sympathetic and parasympathetic nerves Sympathetic innervation of the thyroid may provide for prompt, short-term alterations in the rate of thyroid hormone secretion. Endocrine Thyroid can also respond to TSH releasing histamine and serotonin, which may directly initiate thyroid hormone secretion or increase blood flow.

Copyright © 2014 John Wiley & Sons, Inc. All rights reserved. TH Synthesis T3 and T4 are synthesized and secreted in an 8 step process. Thyroid hormone biosynthesis and secretion. Iodide (I–) is transported into the thyroid follicular cell by the sodium/iodide symporter (NIS) in the basal membrane and diffuses passively into the lumen through the iodide channel called pendrin (P). Thyroglobulin (TG) is synthesized by microsomes on the rough endoplasmic reticulum (ER), processed in the cisternae of the ER and the Golgi where it is packaged into secretory granules and released into the follicular lumen. In the presence of hydrogen peroxide (H2O2) produced in the luminal membrane by thyroid oxidase (TO), the thyroid peroxidase (TPO) oxidizes iodide, which reacts with tyrosine residues in TG in the follicular lumen to produce monoiodotyrosyl (MIT) and diiodotyrosyl (DIT) within the peptide chain. The TPO reaction also catalyzes the coupling of iodotyrosines to form thyroxine (T4) and some triiodothyronine (T3, not shown) within TG. Secretion of T4 begins with phagocytosis of TG, fusion of TG-laden endosomes with lysosomes and proteolytic digestion to peptide fragments (PF), MIT, DIT, and T4. T4 is released from the cell at the basal membrane. MIT and DIT are deiodinated by iodotyrosine deiodinase (ITDI) and recycled. Copyright © 2014 John Wiley & Sons, Inc. All rights reserved.

TH Synthesis Oddities Thyroxine (T4), the major secretory product, is not the biologically active form 2. Thyroid hormones are covalently bound to iodine. Availability of iodine is often limited so cellular mechanisms have evolved for utilization and conservation of I2 Thyroid follicular cells are able to trap I2 at the base of the cell and transport it against an electrical gradient across the cell. Accumulation of I2 by the thyroid requires energy.

TH Synthesis Oddities 3. TH’s are partially synthesized extracellularly Luminal surface of follicular cells TH is stored in the follicular lumen – an extracellular compartment 4. TH’s are doubly secreted The precursor molecule, thyroglobulin, is released from apical surface of follicular cells into the lumen Then…it is taken up again by the follicular cells and degraded. This releases T4/T3 which are then secreted into the blood from the basolateral surface of follicular cells

Copyright © 2014 John Wiley & Sons, Inc. All rights reserved. TH Actions Thyroid hormones: Increase basal metabolic rate (BMR) Help maintain normal body temperature Stimulate protein synthesis Increase the use of glucose and fatty acids for ATP production Upregulate beta (β) receptors that attach to catecholamines Work with hGH and insulin to accelerate body growth Copyright © 2014 John Wiley & Sons, Inc. All rights reserved.

Copyright © 2014 John Wiley & Sons, Inc. All rights reserved. TH Release Thyrotropin-releasing hormone (TRH) Hypothalamus Thyroid-stimulating hormone (TSH) Anterior pituitary Thyroid gland is stimulated to synthesize and release Thyroid hormones (T3/T4) 5 step process. Copyright © 2014 John Wiley & Sons, Inc. All rights reserved.

Copyright © 2014 John Wiley & Sons, Inc. All rights reserved. Thyroid Gland

Control of TH Secretion T4  negative feed back on TSH & TRH Exposure to cold activates the AP-thyroid axis. Rapid release of TSH in infants and rats (not in adult humans). An acute neuroendocrine reflex exists for TSH release in mammals and human infants Mediated by peripheral sensory receptors then relayed to the hypothalamus where stimulation of TRH release occurs

Important TH Functions TH influence most bodily functions and are often permissive for the actions of other hormones. TH are obligatory with GH for early growth and development. TH are unique in that they exert effects within almost every tissue of the body throughout life.

Copyright © 2014 John Wiley & Sons, Inc. All rights reserved. Thyroid Gland

Copyright © 2014 John Wiley & Sons, Inc. All rights reserved. Parathyroid Glands Located on the posterior aspect of each lobe of the thyroid gland are 2 parathyroid glands (one inferior and one superior)- total of 4. Copyright © 2014 John Wiley & Sons, Inc. All rights reserved.

Parathyroid Glands Parathyroid glands contain 2 types of cells: Copyright © 2014 John Wiley & Sons, Inc. All rights reserved. Parathyroid Glands Parathyroid glands contain 2 types of cells: Chief cells (principal cells) produce: Parathyroid hormone (PTH, parathormone) Oxyphil cells -function unknown in normal parathyroid glands; secrete excess PTH in cases of parathyroid cancer PTH is the single most important hormone for controlling blood calcium. Blood calcium low: PTH stimulates osteoclasts, calcium reabsorption in kidneys, activation of vitamin D for digestive uptake of calcium

Copyright © 2014 John Wiley & Sons, Inc. All rights reserved. Parathyroid Glands Calcitonin produced by the thyroid gland works in conjunction with PTH and calcitriol to regulate calcium homeostasis. Copyright © 2014 John Wiley & Sons, Inc. All rights reserved.

Copyright © 2014 John Wiley & Sons, Inc. All rights reserved. Parathyroid Glands