THE PITUITARY GLAND
Study guide/Handout

Web address: http://www.cytochemistry.net/Endocrine_System/pituitary.htm

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

To help you with your study of the Endocrine System, read pp 301-309, Chapter 13, Gartner and Hiatt, W.B. Saunders, Philadelphia, PA follow the guide in the questions below.  Use the text in this handout (which is also on the above web site) for the answers.  The handout may also refer you to photos in Gartner and Hiatt;  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 hypophysis?

1. How do endocrine cells communicate with their target system? How do neuroendocrine cells communicate with their targets? 
2. Distinguish autocrine, paracrine, and endocrine regulation?   What is juxtacrine regulation?
3. Locate the hypophysis and name its various parts.
4. What is the embryologic origin of each of the various parts of the hypophysis?
5. Compare and contrast the blood supply to the posterior and anterior lobes.
6. How is the neurovascular link in the stalk/infundibular region designed to support the function of the pituitary?
7. Describe the organization of the posterior lobe and infundibular stalk. Where are oxytocin or vasopressin produced and packaged? What are Herring Bodies?
8. The anterior pituitary cells produce protein, peptide or glycoprotein hormones.  What organelles would you expect to find in the cells?
9.  How are the pars distalis or anterior lobe cells organized to perform their functions. Where are each of the major hormones stored and what is the function of each hormone?  
10. What can happen if there is too much GH before puberty?  What can happen if there is too much GH after puberty?
11. What is the function of the pars tuberalis and pars intermedia (intermediate lobe?)
12. What are the various routes through which anterior lobe cells can be regulated?
13 Distinguish positive and negative feedback as applied to the endocrine system
14. Compare and contrast the anatomical pathways for oxytocin or vasopressin with those that send releasing hormones to the anterior lobe.
 

A. INTRODUCTION AND DEFINITIONS

For illustrations, consult the brief slide presentation at: http://www.cytochemistry.net/Endocrine_System/Endocrine_System_Intro.htm
(note: these are best viewed with Explorer 4.0 or greater.)

1. Endocrine gland/cells: secrete product called hormone into the blood stream that affects other cells or systems.
2. Hormone: from root "horare" ="to arouse". Hormones are chemicals that may stimulate, inhibit, or maintain status quo of a system or group of cells. May be diverse--proteins, peptides, amines, steroids.
3. Neuroendocrine: A nerve cell produces a hormone and secretes it into the blood stream. The nerve cell itself may be affected by hormones from other nerve or endocrine cells. 
4. Mechanisms of Regulation  
a. Endocrine: Cell in one organ secretes a hormone that travels via blood stream to another organ and regulates a target cell
b. Paracrine: Cell in a given organ secretes a hormone that affects another cell type in same organ.
c. Autocrine: Cell produces hormone that regulates cells in its own population, or family.
d. Juxtacrine: Cell produces a hormone or growth factor that regulates its neighboring (adjacent) cell.  May be a tethered ligand, bound in the membrane of the signaling cell.

B. ANATOMY OF THE HYPOPHYSIS

For more illustrations, consult the slide presentation at:
http://www.cytochemistry.net/Endocrine_System/Pituitary_lecture_slides.htm

(note: these are best viewed with Explorer 4.0 or greater.)

1. Locate the hypophysis: This gland is in a depression at the base of the skull in the sphenoid bone called the "sella turcica". Connected by a stalk of neural tissue to the brain.  (Figure in text)

2. Major divisions of Adenohypophysis:

Major cellular portion is the pars distalis or anterior lobe.
A small collar of cells around the stalk is called the pars tuberalis. 
The section attached to the neurohypophysis is called the pars intermedia, or intermediate lobe.

3. Divisions of Neurohypophysis:

Fibrous process attached to the adenohypophysis is called the infundibular process or posterior lobe, or pars nervosa.  
Stalk connecting pituitary to brain is called the infundibular stalk.  
Region of nervous tissue at the top of the stalk (floor of the third ventricle) is called median eminence.

For more illustrations, check out your text or http://www.cytochemistry.net/Endocrine_System/Pituitary_lecture_slides.htm
(note: these are best viewed with Explorer 4.0 or greater.)

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C. EMBRYOLOGY: What is the origin of each of the parts of the hypophysis?

pitdraw2.jpg (26752 bytes)

Rathke's pouch grows up from mouth to meet brain and a process grows down from the diencephalon of the brain.  Rathke's Pouch becomes the Adenohypophysis. The neural process  from the diencephalon becomes the Neurohypophysis.  Eventually loses connection with the mouth.  But the stalk retains its connection with the brain.

D. BLOOD SUPPLY TO THE HYPOPHYSIS.

See slide show illustrating the pituitary blood supply (note: these are best viewed with Explorer 4.0 or greater.):

Adenohypophysis- Superior hypophyseal arteries from internal carotids and the posterior communicating artery of the circle of Willis branch to form a capillary plexus in the pars tuberalis and median eminence region.

These capillary loops distribute throughout the stalk/median eminence region. What might be the significance of this distribution?  (Answer. This increases the surface area so that many axonal endings can lie against the capillaries). 

These capillaries then send long portal vessels down to the anterior lobe/pars distalis to communicate with a second capillary bed. This second capillary bed is a sinusoidal type (fenestrated with diaphragms) and provides the supply to the cells of the anterior lobe. Venous drainage is to Y-shaped veins that may be shunted into the posterior lobe. From there, drainage is to the cavernous sinus.

Key concept:
Blood supply sets up an important neurovascular link between the hypothalamus and the pituitary gland. Axonal endings in the median eminence contain stores of regulatory hormones that control the anterior pituitary cells. At the appropriate time, these are secreted and carried down the portal vessels to the anterior lobe target cell. The short distance makes this an efficient delivery system for these hormones.

Neurohypophysis- Inferior hypophyseal arteries, also from internal carotid, penetrate the posterior lobe and branch to form a capillary bed. Drainage is to the cavernous sinus. A few inferior hypophyseal arteries also supply the outer part of the anterior lobe. For the most part, the arterial supply is separate from that of the adenohypophysis. However, the venous supply from the anterior lobe may connect with that from the posterior lobe. This vascular link may provide regulatory hormones from the anterior lobe that affect secretion from the posterior lobe.
 

E. REGULATION OF THE ANTERIOR LOBE CELLS

pitdraw5.jpg (28566 bytes)Neurovascular links: How do the anterior pituitary cells communicate with the outside world and regulate one another?

1) Communication from the brain: Nerve cells in the hypothalamus (in specific nuclei) produce hormones that regulate each of the anterior pituitary cells. Most of the above cell types have a releasing hormone (named after the cell it stimulates) that is produced in a set of neurons and sent via an axon to the median eminence. There it is released into the pituitary portal blood. Some of the cells have an inhibitory hormone that also regulates secretion. These hormones are stored in granules in the axons until they are released. This is the neurovascular link we talked about earlier. The capillary network in the pituitary stalk provides a broad surface area for the secretion of these hormones. Some hormones may stimulate more than one pituitary cell. Some cells have more than one stimulating hormone. In that case, the axons may store these hormones together so that the cells receive maximal stimulation.

2)
Communication from the target cells.. Target cells in the periphery may secrete hormones into the blood stream that will affect the pituitary cells.  This is called "feedback".   If their products stimulate the pituitary cell, they are inducing positive feedback; if they inhibit the pituitary cell, they  induce negative feedback.  

Note: Removal of a target organ (such as the ovary, testes, adrenal, or thyroid) removes a source of feedback and has major effects on the pituitary cells. Often it stimulates both hypertrophy and hyperplasia of specific cell types because the pituitary "thinks" that it needs to give the target organ more stimulation.  Thus, that feedback is very valuable to let the pituitary know how much stimulation the body needs. 

pitdraw4.jpg (33068 bytes)

F. ORGANIZATION OF THE PARS NERVOSA

1. How is the posterior lobe organized?  The posterior lobe consists of axons, and axonal endings and glial cells (called pituicytes). In other words, it is basically white matter. The nerve endings store two peptide hormones:

a) oxytocin which is important during uterine contractions (stimulates myometrium) and lactation (stimulates myoepithelial cells)  and

b) antidiuretic hormone (ADH) which stimulates water absorption by the collecting tubules. ADH is also called vasopressin because it is a vasoconstrictor. These hormones are stored in secretory granules in the nerve endings in the posterior lobe and released at the appropriate time into the capillaries.

2) Where are the cell bodies that belong to these axons? These cell bodies are in the paraventricular and supraoptic nuclei in the hypothalamus (which is a brain region on the floor of the third ventricle). Different cells produce oxytocin or vasopressin. Oxytocin and vasopressin are synthesized on the rough endoplasmic reticulum and packaged in granules by the Golgi complex. Then they are sent down the axon which travels to the median eminence. Some of the axons end there. Others go down to the posterior lobe and end on the capillaries in this region. Some endings are so large, they accumulate many storage granules. These endings are called Herring Bodies.

3) How are these cells controlled? Control of release of oxytocin can be at all points in the circuitry, at the site of the cell body in the hypothalamus, at the median eminence, and at the site of the ending in the pars nervosa/posterior lobe. Control can be either via blood supply or via direct nerve fiber communication up in the brain.

pitdraw6.jpg (93824 bytes)G. CYTOLOGY AND HISTOLOGY OF THE ANTERIOR LOBE 

How are the anterior pituitary cells designed to perform their function?  

All of the anterior lobe endocrine cells produce protein/peptide hormones.  What organelles would you expect to find?

All the hormone producing cells in the pituitary contain rough endoplasmic reticulum, a prominent Golgi Complex, and secretory granules in which the hormone is stored. When stimulated, the cells release the granules and  also begin to synthesize more of the hormone.  The cells may be polarized so that the secretory apparatus points towards the side adjacent to the blood vessel.  Many of the cell types produce distinctive granules so that they can be identified at the electron microscopic level by the size and shape of their granules. 

How are the cells organized to produce the different hormones? Based on staining characteristics at the light microscopic level, the cell are divided into 3 classes. Red or orange staining cells are called acidophils, blue or purple cells are basophils and cells with little stain are called chromophobes.   Consult your text for photographs.   

 The terms acidophilia or basophilia, when applied to the pituitary, actually were derived from special stains applied to the pituitary that turned each cell type a different color.  The red cells were called acidophils, the bluish/purple cells were called basophils, colorless cells were called chromophobes..  Actually however, the researchers in those days used a set of acid dyes and the staining characteristics have NOTHING to do with true "acidophilia and basophilia".  In truth, the best basophils are the "acidophils".  What does it mean when a cell is showing a high degree of "basophilia" (with the use of basic dyes). 

Clinical note: Why is it important to know this?  Pituitary tumors have the same classification and reference is often made to acidophilic adenomas, etc. It is important to recognize that this tinctorial stain helps only to narrow down a potential product from a tumor. A Tumor can actually be multihormonal in that it may be derived from a multipotential stem cell.   

Researchers have linked individual hormones to these different classes of cells by immunolabeling them for the hormones and by observing cytological changes in different physiological states. You will only  be able to distinguish pituitary cell types for sure on slides that are  immunolabeled for the hormones.   However, you can distinguish acidophils, basophils and chromophobes and arrive at the following categories:

  Acidophils: Most abundant; usually in the posterolateral region of the human pituitary. 
Produce growth hormone/somatotropin (GH). These cells are ovoid and very active during growth and development. GH stimulates growth of long bones (where does this occur?).
Another group of acidophils is more abundant during pregnancy and lactation. These produce prolactin which helps in the production of milk and during lactation. 
Some acidophils produce both growth hormone and prolactin; they are called mammosomatotropes. (mammo" stems from the word mammary gland which reflects the prolactin function).

Clinical note: A GH secreting tumor before puberty stimulates growth in length of long bones at the epiphyseal plate and "Gigantism".  After puberty, the epiphyseal plates have closed.  A GH tumor stimulates bone thickening (intramembranous bone formation) and the distinctive changes of "Acromegaly".  Examples will be shown in lecture.

Basophils:  
One type produces adrenocorticotropin (ACTH) and beta-endorphin. ACTH stimulates the adrenal cortex "zona fasciculata" during the flight or fight response to stress. Beta-endorphin is an internal analgesic, which may also aid the system during the stress response. The runner's "high" stems from endorphins.
The second type produces the gonadotropins. Luteinizing hormone (LH) stimulates ovulation and formation of the corpus luteum; or testosterone production by the Leydig cells. Follicle stimulating hormone (FSH) stimulates the growth and development of the follicle and the function of the Sertoli cells in the testes. 
The third type of basophil produces Thyroid stimulating hormone (TSH) which stimulates the thyroid gland to regulate basal metabolism in the body. 
Some basophils produce more than one of these hormones.
  Chromophobes: These may be resting or reserve cells. Or they may have secreted all of their product. Probably not a separate cell type, but a poorly granulated version of either a basophil or an acidophil.  Could be secreting very actively.

G. Pars tuberalis: consists of gonadotropes and thyrotropes (basophils) although the proportions vary with the species. These are basically a layer of anterior lobe cells wrapped around pituitary stalk. Don't really know the significance.

H. Pars intermedia: consists of corticotropes that produce another peptide called melanocyte stimulating hormone (MSH) (in addition to ACTH and beta endorphin). Mostly gone in humans (adult), although present in fetal state.   Prominent in lower mammals and may receive innervation.  Significance uncertain except it seems to respond to certain types of stress (sound).

 Consult Table 19.1 in Burns and Cave for a nice listing of all of the above cell types and hormones. 

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Some cutting edge research "stuff": The anterior pituitary is like an endocrine "neighborhood".  Cells visit with each other, work together to support an outside system (like "block parties, quilting bees"), or provide support, inhibition or stimulation for each other. Collectively, this working together or "synergy" may produce more efficient regulation of the endocrine system. The following are some examples:

Paracrine Communication within the pituitary. Pituitary cells control other pituitary cells locally by secreting hormones or growth factors. This is called paracrine or juxtacrine regulation.   For example, subsets of all pituitary cell types produce epidermal growth factor and other growth factors which may stimulate and facilitate function locally. 
Autocrine regulation is another form of local control. Some of the cells may be able to shut secretion down in their own population if the blood level of the hormone gets too high. This is also called ultrashort-loop negative feedback.   Perhaps only certain of the cells "get to secrete".  The rest may be shut down unless more is needed.  
Transitional support for one another.  It is believed that subsets of most pituitary cell types are multipotential and can add to the population of another cell type as needed.  Subsets can also divide and add to the population.  This might be particularly important if you needed a "cocktail" of hormones to serve different functions.  For example, supposing you are stressed in a cold environment, you might need ACTH and Beta endorphin in response to stress and pain associated with cold.  You would also need TSH to stimulate the thyroid to raise the metabolic rate. We are learning that there may be cells that can serve both functions and produce both TSH and ACTH or Beta endorphin in a  cocktail that can meet the body's need to respond appropriately to cold stress. 

In summary, the anterior pituitary cells produce the 6 main hormones described above. In addition, numerous other types of peptides (some of which are also found in the brain and GI tract and all the major growth factors are produced by some of the pituitary cells (e.g., Nerve growth factor, epidermal growth factor, fibroblast growth factor, etc). These peptides and factors may be used to communicate with either the periphery, brain or locally with each other as paracrine or autocrine regulators.

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