Thyroid and Parathyroid Glands
Study Guide/Handout

http://www.cytochemistry.net/Endocrine_System/thyroid_and_parathyroid.htm

Gwen V. Childs, Ph.D.
Shorey 9/32
childsgwenv@uams.edu

To help you with your study, follow the guide in the questions below.   The guide also refers to a set of lecture slides at:  Thyroid and Parathyroid Lecture Slides  Use the text in this handout and read pp 310-315, Gartner and Hiatt.  

The handout may also refer you to photos in Gartner and Hiatt, W.B. Saunders, Philadelphia;  and diagrams and tables in Histology and Cell Biology (ACE the Boards) Chapter 19, Burns B and Cave, D, Mosby, St. Louis. 

Test Yourself: How much do you know about the Thyroid and Parathyroid?

1) Locate the thyroid gland. 
2) Compare the region of origination (embryology) of the thyroid with that of the pituitary gland.
3) Review the blood supply of the thyroid.
4) How would you distinguish the thyroid?
5) If you eat a low iodine diet, you become hypothyroid.  Do you know why?
6) Define the steps taken by the thyroid follicular cell to produce and store its hormone, thyroxine or tri-iodothyronine.  
   a. Define each organelle system involved and the steps in the synthesis.
   b. How and where is the thyroid hormone (thyroxine, T4 or tri-iodothyronine, T3) stored? 
   c. Where is it iodinated? 
   d.What is the significance of the colloid in the follicles?
   e. How many thyroid hormone molecule  production sites are found in one thyroglobulin molecule? 
7) What happens when the thyroid epithelial cells are stimulated by TSH? Where is TSH produced?
8) Define the steps taken by the thyroid follicular cell to secrete thyroid hormone. What organelles are involved?
9) What happens to the thyroid gland if we have a low iodine diet?

Calcium regulation

Parafollicular cells

1) What are parafollicular cells and where are they found?
2) What hormones are produced by the parafollicular cells and what is their function? What bone cells are affected?

 The Parathyroid Glands

1) Where would you find the parathyroid glands? What histological features would you use to distinguish them?
3) Describe the chief cells and their function? What is the target cell (s) for the hormone product? How are the chief cells regulated?
4) What are oxyphil cells and how would you identify them?

Locate the thyroid gland in the body.

Isthmus is midway between the "Adams apple" and the suprasternal notch.
Gland=two lateral lobes + an isthmus + a pyramidal lobe.  See Figure 13-6, Gartner and Hiatt.

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From what region does the thyroid  originate?

Downward growth from the floor of the pharynx.  Structure called the
"Thyroglossal duct".   (Recall that the pituitary originates from the roof of the
pharynx). Grows down in front of the trachea, bifurcates to form the lateral lobes.

Review the blood supply of the thyroid.

From branches of the Common carotid artery (superior and inferior thyroid arteries and the thyroid ima artery).
Drains into the Internal jugular vein. 

How would you distinguish the thyroid? 

Made up of "sacs" called follicles lined with epithelial cells that are cuboidal-columnar. Follicles are filled with "colloid".  At the base of the cell are the fine capillaries. At  the apex of the cells you have the colloid. Very little connective tissue between the follicles except in certain places where there are calcitonin cells (to be discussed later)

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If you eat a low iodine diet, why do you become hypothyroid?

Thyroid hormone is actually made of two amino acids called tyrosines that are linked together.  When they are linked, the structure is called a "thyronine".  In order to be biologically active, the thyronine  molecules must have at least three iodine attached to the ring structures.  This is made by iodinating the tyrosines.   The bottom line is: even if the two amino acids are put together, these molecules are not biologically active if they lack iodine.

What organelles do the thyroid follicular cells use to make thyroid hormone?

The thyroid follicular cells produce a 660,000 MW glycoprotein called thyroglobulin.  It is produced by the organelle system that is designed to synthesize, package, and secrete glycoproteins. This would include the rough endoplasmic reticulum and the Golgi complex. The thyroid hormones are stored either as iodinated amino acids (tyrosines) in the thyroglobulin molecule.   

How do the cells produce and store the thyroglobulin?

Refer to the following web site for a cartoon of the steps.  Thyroid and Parathyroid Lecture Slides

  • Step 1.  Uptake of Iodide (active transport across basement membrane).  Iodide is then oxidized by thyroid peroxidase so it can be attached to thyroglobulin.  This happens at base of cell from the capillaries
  • Step 2.  Uptake of amino acids, sugars. Also at the base of the cell, next to the capillaries.
  • Step 3. Production of thyroglobulin:  mannose is one of the sugars added in the rough endoplasmic reticulum; galactose and fucose (for example) are added in the Golgi complex. 
  • Step 4. Packaging of the thyroglobulin by the Golgi complex. This happens above the nucleus.
  • Step 5. Secretion into the colloid by exocytosis.  See the top of the cells.
  • Step 6. Production of iodinated thyroglobulin:  As it is being secreted, the tyrosine residues on the thyroglobulin are iodinated, just outside the cell, near the plasma membrane.  Also, see the top of the cells.
  • Step 7. The thyroglobulin with its iodinated amino acids (tyrosines) is stored in the colloid.   

    Just for fun: How many thyroid hormone molecule production sites are stored in one thyroglobulin molecule?

    • Two thyroglobulins are put together in the Golgi complex (creating a dimer) just before secretion.  
    • The gene for each thyroglobulin monomer codes for  four sites that contain enough tyrosines to support production of the hormones, one is at the N terminal and 3 are at the C terminal. 
    • So, there may be a total of 8 sites. Not all of these contain tyrosines that are linked together, however to make the thyronines.  A number are simply MIT's and DIT's.  

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What happens when the thyroid epithelial cells are stimulated by TSH? Where is TSH produced?

TSH is produced in the pars distalis of the pituitary gland (anterior lobe) by basophils called thyrotropes (or Thyroid stimulating hormone cells).  These cells are in turn stimulated by thyrotropin releasing hormone (TRH) from the hypothalamus.  TSH stimulates all of the processes described above, including gene expression and iodine uptake. 

Define the steps taken by the thyroid follicular cell to secrete thyroid hormone. What organelles are involved?

  • Step 1. Stimulation by TSH.  This process is ongoing along with the synthesis process in the same cells.  The cartoon above shows it in two cells for the sake of simplicity.  TSH also stimulates growth in the thyroid follicular cells (to a columnar cell type).  This happens at the bottom of the cell where TSH interacts with the receptor.
  • Step 2. Uptake into vacuoles by pinocytosis.  This happens at the top of the cell where it touches the colloid.
  • Step 3. Vesicles carrying lysosomal enzymes merge with vacuoles, forming lysosomes.  This happens near the cell middle.
  • Step 4. Thyroglobulin is broken down releasing the thyroid hormones.  The remaining iodinated thyrosines are deiodinated so they and the iodine can be recycled. 
  • Step 5. Thyroid hormones  are secreted from the lateral and basal surfaces of the cell. 

What happens to the thyroid gland if we have a low iodine diet? What is a goiter?

Clinical note: Thyroid cells grow taller as they are stimulated.  They also make more colloid. It is possible to create a much larger thyroid by hyperstimulation.  This is called a goiter.  There are different kinds of goiters, depending on the problem.  One kind could form if the iodine in the diet was too low. The thyroid could make thyroglobulin, but not iodinate it.  If thyroid hormone levels in the blood stream drop, then the pituitary thinks it needs to secrete more TSH.  As more TSH is secreted, the thyroid follicular cells grow and make more thyroglobulin.  The result is a much larger thyroid gland, but not more thyroid hormone. So, the pituitary gets the message again that more stimulation is needed, and TSH continues to be secreted.  This is a great example of what happens when "negative feedback" is shut down.

Calcium Metabolism:  Maintain proper calcium levels.

More Photos and cartoons can be found at:  Thyroid and Parathyroid Lecture Slides

What are parafollicular cells and where are they found?

Parafollicular cells are also called "C cells".  They are found in the interstitial spaces outside the thyroid follicles in the middle third of the lateral lobes.  As all endocrine cells, they lie next to capillaries so they can secrete their hormone into the bloodstream.  

The hormone they produce is "calcitonin".  They respond to high blood levels of calcium.  When calcium levels are too high, they secrete calcitonin and this hormone inhibits osteoclastic activity. What is the function of osteoclasts?    Osteoclastic activity releases calcium that goes into the blood stream for use by the cells in the body. How does it do this?

Calcitonin is a polypeptide so it is produced by rough endoplasmic reticulum and stored in secretory granules.  The cells can only be identified with certainty by immunolabeling for calcitonin. 

C Cells or parafollicular cells labeled for calcitonin.  You can see the outlines of the thyroid follicular cells lining the follicles.

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Where would you find the parathyroid glands? What histological features would you use to distinguish them?

There are at least 4 parathyroid glands found embedded in the capsule of the thyroid at its dorsal surface. 

The glands are distinguished by the presence of the following:

  • Clumps of adipose cells
  • Clusters of acidophilic cells called "oxyphil cells"
  • Scattered light basophilic or clear "chief cells".

The photos in the text show each of the cell types well.  Below are drawings of oxyphil and chief cells. 

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Describe the chief cell and its function? What is/are the target cell (s) for its product? How are the chief cells regulated?
 

Chief cells are lightly staining cells that make parathyroid hormone.  This is a polypeptide so it is made on rough endoplasmic reticulum, packaged by the Golgi complex, and stored in secretory granules. 

A drop in calcium levels will stimulate release and synthesis of parathyroid hormone.  Therefore, regulation is by levels of serum calcium. 

Parathyroid hormone then works on three target cell types to raise serum calcium. These include:

  • Osteoblasts
  • Kidney proximal tubule cells
  • GI tract absorptive cells

What are oxyphil cells and how would you identify them?

Oxyphil cells are usually in clusters.  They are distinguished by dense red (acidophilia) staining and a dense, centrally located nucleus.  At the electron microscopic level, the above drawing shows that  the cytoplasm is filled with mitochondria. 

What other cell type in the body has this many mitochondria?

The function of oxyphil cells is not known.  However, it clearly functions to help you identify the parathyroid gland, since its presence is diagnostic of the gland.

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Last update: 10/13/2001
Web address: http://www.cytochemistry.net/Endocrine_System/thyroid_and_parathyroid.htm

Gwen V. Childs, Ph.D.
University of Arkansas for Medical Sciences
Shorey 9/32; (501) 686-7020
For questions or comments email:  childsgwenv@uams.edu

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