THE HYPOPHYSIS

February 17, 1998

Gwen V. Childs, Ph.D.

10-104 MRB, X1942

Reading Assignment: Bloom and Fawcett, Chapter on Hypophysis

TEST YOURSELF:

1. How do endocrine cells communicate with their target system? How do neuroendocrine cells communicate with their targets?
2. What is the embryologic origin of each of the various parts of the hypophysis?
3. Distinguish autocrine, paracrine, and endocrine regulation?   What is juxtacrine regulation?
4. Describe the organization of the posterior lobe and infundibular stalk. Where are oxytocin or vasopressin produced and packaged? What are Herring Bodies?
5. 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?
6. How is the neurovascular link designed to enhance the function of the pituitary?
7. What are the various routes through which anterior lobe cells can be regulated?
8 Distinguish positive and negative feedback as applied to the endocrine system.
9. Compare and contrast the anatomical pathways for oxytocin or vasopressin with those that send releasing hormones to the anterior lobe.
10. Compare and contrast the blood supply to the posterior and anterior lobes.

A. INTRODUCTION AND DEFINITIONS.

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 signalling cell..

B. ANATOMY OF THE HYPOPHYSIS

1. Location: 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.

2. Major divisions of each region:

a.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.

b.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.

 

 

 

C. EMBRYOLOGY

Rathke's pouch grows up from mouth to meet brain and a process grows down from the diencephalon. Rathke's Pouch becomes the adenohypophysis. The neural process becomes the neurohypophysis.

D. BLOOD SUPPLY TO THE HYPOPHYSIS.

a.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 which then sends capillary loops to the stalk/median eminence region. This increases the surface area so that many axonal endings can lie against the capillaries. These capillaries send long portal vessels down to the anterior lobe 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.

Bood 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. 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: 1) oxytocin which is important during uterine contractions (stimulates myometrium) and lactation (stimulates myoepithelial cells) and 2) 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. Different cells produce oxytocin or vasopressin in each nucleus. 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.

F. CYTOLOGY AND HISTOLOGY OF THE ANTERIOR LOBE 

How are these endocrine cells designed to perform their function? All of the anterior lobe endocrine cells produce protein/peptide hormones. Therefore, they 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 may 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. Tumors, therefore, have the same classification. This helps only to narrow down a potential product from a tumor. A Tumor can actually be multihormonal. 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. Thus the cells are further divided as follows: You will not be able to distinguish the subcategories on slides that are not immunolabeled for the hormones.   However, you can distinguish acidophils, basophils and chromophobes.

1) Acidopils: Most abundant produce growth hormone/somatotropin (GH). These cells are ovoid and very active during growth and development. GH stimulates growth of long bones (at epiphyseal plates); Another group 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.

2) Basophils: One type produces adrenocorticotropin (ACTH) and beta-endorphin. ACTH stimulates the adrenal cortex 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 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.

3) 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.

G. Pars tuberalis: consists of gonadotropes and thyrotropes (basophils).  Anteior lobe cells wrapped around pituitary stalk.

H. Pars intermedia: consists of corticotropes that produce another peptide called melanocyte stimulating hormone (in addition to ACTH and beta endorphin). Mostly gone in humans (adult), although present in fetal state.   Prominent in lower mammals.

I. REGULATION OF THE ANTERIOR LOBE CELLS

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 hypothalmus (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. If their products stimulate the pituitary cell, they are inducing positive feedback; inhibitory hormones induce negative feedback.

Feedback: The way hormones communicate with target or source cells. Positive feedback=stimulatory and negative feedback=inhibitory.

3) Communication within the pituitary. Pituitary cells control other pituitary cells locally by secreting hormones. This is called paracrine regulation. For example, some gonadotropes produce renin and angiotensin II is found in the same granules with LH. A-II can stimulate the release of both ACTH and prolactin. Thus, if one stimulates gonadotropes, one may also activate corticotropes and prolactin cells.   Subsets of all pituitary cell types produce epidermal growth factor and other growth factors which may stimulate and facilitate function locally.

4) 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. Or, we are now learning that subpopulations of a pituitary cell type may actually produce separate activating or inhibiting hormones for subsets of cells in the same family. An example in the gonadotrope population are the subsets that produce stimulatory peptides for FSH called activin and also inhibitory peptides called inhibin and follistatin.

5) 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.  This might be particularly important if you need a "cocktail" of hormones to serve different functions.  For example, if 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. So, there appear to 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.. 

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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; e.g. gastrin) 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.