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Histology - Lecture 1 - Intro to Endocrine System and Pituitary Gland

Note. Make sure you know all of the learning objectives.
Fundamental structural differences between endocrine glands and exocrine glands.

Major structural differences between the cell types that secrete peptide hormones versus steroid hormones.

Basic functions and structures/subdivisions of the pituitary gland.

Major cell types of the pituitary gland and how to recognize them.

How the vasculature of the pituitary gland is organized to allow communication within the gland and to the rest of the body.

Fundamentals of releasing and inhibiting factors and pituitary gland hormones.

Introduction to disorders that arise due to disruptions of pituitary gland function.
What is the role of the endocrine system?
To mediate cell-cell communication necessary for integrating functions of different organs and tissues.
What are hormones?
Chemical messengers.
What are glands?
The tissues that are specialized for the secretion of hormones.
What six things can the endocrine system participate in?
1. Reproduction.
2. Growth and development.
3. Adaptation to hostile environment.
4. Control of the composition and volume of extracellular fluid. (Think ADH).
5. Control of energy production.
6. COntrol of the digestive tract and accessory tissues.
Developmental what do endocrine and exocrine glands develop from?
Epithelial sheets.
What is the difference between endocrine and exocrine secretion?
Exocrine secretion delivers its products into DUCTS.

Endocrine secretion releases hormones into blood or lymph, which then reaches the target tissues.
What are the two important properties of endocrine secretion that are important to understand?
1. Endocrine signaling is relatively SLOW. This is since endocrine signaling depends upon diffusion and blood flow. This can take minutes to days.

2. Endocrine hormones act at very LOW CONCENTRATIONS. This is since hormones are diluted in the blood system.
Describe the development of endocrine glands.
These are in the embryo as tubular invaginations or outgrowths of epithelial sheets. As the development proceeds their connection to the original epithelial sheet is lost.

Endocrine glands become penetrated by blood vessels. A rich capillary plexus forms in close relationship to secretory cells of the gland. This allows for endocrine function.
Describe the development of the exocrine glands.
These are in the embryo as tubular invaginations or outgrowths of epithelial sheets. As the development proceeds their connection to the original epithelial sheet is retained.
What type of capillaries are associated with most endocrine glands?
Fenestrated capillaries.

Recall: the fenestrae are 60-80nm in diameter and are spanned by an ultra thin diaphragm of radially oriented fibrils that allow small molecules and limited amounts of protein to diffuse.

Fenestrated capillaries have a continuous basal lamina that is continuous with pericytes.
What is the purpose of fenestrated capillaries?
To facilitate rapid exchange of fluid and small molecules across the capillary wall.

Recall: the kidney has fenestrated capillaries.
What type of capillaries are found in the adrenal cortex and the pituitary gland?
Sinusoidal (discontinuous) capillaries.

Recall: these have a large lumen that is 30-40um in diameter.

They possess number large fenestrae that LACK diaphragms.

The endothelial wall may be discontinuous and the basal lamina is discontinuous.

This enhances the change between the blood and surrounding tissue.
What are trophic hormones?
These are hormones produced by the anterior pituitary.
What are the major glands of the endocrine system?
1. Pituitary gland.
2. Adrenal gland.
3. Thyroid gland.
4. Parathyroid gland.
5. Gonads.
6. Pineal gland.
7. Pancreatic islets.
8. Intestinal mucous (CCK, gastrin)
9. Epithelial lining of the respiratory system.
10. Placenta.
What type of receptors are TSH and catecholamine receptors?
These are cell-surface receptors.
What type of receptors are insulin and GH receptors?
Catalytic receptors. Both insulin and GH use tyrosine kinase receptors.
What type of receptors are thyroid hormone and estrogen receptors?
Nuclear receptors.
Histologically how do you differentiate and endocrine cell from an exocrine cell?
Exocrine cells have more RER and secretory granules. The RER allows them to synthesize large amounts of protein. The secretory granules are mainly apically located and this is how the protein products are released. (So these cells are polarized) These secretory cells overlie a highly-developed Golgi apparatus, which modified the secretory granules.

Endocrine cells only have a modest amount of RER, since they don't make much protein. Their secretory granules are found throughout the cells, rather than being concentrated in a pole. Also have a modest Golgi apparatus.

This is consistent with the large differences in the amount of protein being produced by each type of cell.
Histologically how do you differentiate endocrine cells that secrete steroids vs. peptides?
Endocrine cells that secrete steroid hormones are specialized for lipid metabolism.

They have abundant SER. This allows them to make cholesterol and modify it to make steroid hormones.

Have lipid droplets, there cholesterol is stored.

Have numerous mito, which are involved in steroid hormone synthesis. The first step in steroid hormone biosynthesis is cleavage of cholesterol side chain by P450-SCC, a mitochondrial enzyme.
What is unique about the mitochondria of steroid secreting cells?
They have a notable cristae ultrastructure.

Most mitochondria have a flattened lamellar cristae. But steroid secreting cells have tubular cristae. These looks like viruses on TEM.
What part of the brain is the hypothalamus a part of?
The diencephalon.
What is the master gland of the endocrine system?
The pituitary gland.
Describe the development of the pituitary.
The pituitary arises anteriorly from the oral ectoderm (Rathke's pouch) and posteriorly from the neural tissue (the developing diencephalon).
What are the three portions of the anterior pituitary?
1. Pars distalis. This is the bulk of the anterior pituitary.

2. Pars tuberalis (pars infundibularis). This is juxtaposed against the infunibular stalk. For a sheath surrounding it.

3. Pars intermedia. This abuts the posterior pituitary. Also called the intermediate lobe of the pituitary.
What are the parts of the posterior pituitary?
1. Pars nervosa (also called the infundibular process) This consists of axons from the magnocellular neurosecretory nuclei of the hypothalamus. This is the bulk of the lower posterior pituitary.

2. Infundibular stalk. Connects the pars nervosa with the median eminence. Is surrounded by the pars tuberalis of the anterior pituitary.

3. Median eminence. This is often considered to be part of the hypothalamus.
Have a slide that allows you to see a section of the hypothalamus and can check understanding of the gross portions of the hypothalamus.

Take a look at it.
What are the three major cells type of the pars distalis?
The three major cell types are identified on the basis of their staining reactions.

1. Acidophils - 40%, heavily stained, bright red cytoplasma in H&E.

2. Basophils - 10%, paler-staining cytoplasma, blue-ish in H&E.

3. Chromophobes - 50%, only the nucleus is stained in H&E. The cytoplasm doesn't stain.

Note: the cells within the pars distalis are arranged in thick cords, with different cell types intermingled.
What is an acidophil? What is a basophil?
An acidophil likes acid. Eosin is an acid that stains basic structures pink or red.

A basophil likes bases. Hematoxylin is a base that stains acidic structures, like nucleic acids, blue.
What type of hormones are secreted by the anterior pituitary?
The hormones secreted by the anterior pituitary are all of the peptide hormones.
What are the two types of acidophils that are found in the pars distalis?
1. Somatotrophs - These are the most common acidophils. They secrete GH, which is also called somatotrophin.

2. Mammotrophs - These secrete prolactin.
What are the three types of basophils that are found int he pars distalis?
1. Corticotrophs - These secrete ACTH and Lipotropic hormone (LPH), a precursor of beta-endorphin.

2. Thyrotrophs - These secrete TSH.

3. Gonadotrophs - These secrete FSH and LH.
What are the types of chromophobes in the pars distalis?
Some may represent degranulated chromophils and other may be undifferentiated cells.
What type of cells are the pars intermedia?
1. Polygonal basophilic cells - these cells produce several peptides from the preprohormone, Pro-Opiomelanocortin (POMC). This does to make ACTH, Beta-lipotropin, melanocyte stimulating hormone, and beta-endorphin.

2. Colloid-filled cysts lined by cuboidal epithelial cells.
What are the two major cells types of the pars nervosa?
1. Pituicytes.

2. Terminal portions of the axons.

Note: when looking at a histological slide of the pars nervosa you will not see many cells. It will look sparse because most of the space is taken up by the unmyelinated axons.
What are pituicytes?
These occupy 25% of the volume of the pars nervosa and are the only truly intrinsic cell population.

They do NOT secrete hormones, they are supporting cells.
Describe the terminal portions of the axons in the pars nervosa.
These are unmyelinated axons that arise from the cell bodies located in the supraoptic and paraventricular nuclei of the hypothalamus (these are called the magnocellular neureosecretory nuclei).

These contain ADH and Oxytocin, which are complexes to a neurophysin in the terminal swellings of the axons.
What are Herring bodies?
These are the terminal swellings of the axons of the pars nervosa that contain either ADH or oxytocin with its associated neurophysin.

Terminal axonal swellings arising from neuronal cell bodies located in magnocellular neurosecretory nuclei of the hypothalamus.
What are neurophysins?
These are carrier proteins generated from the same precursors as the hormones.

Neurophysin 1 for oxytocin.

Neurophysin 2 for ADH.
Describe the secretion from the posterior pituitary.
Secretion of peptide hormones DIRECTLY INTO BLOOD.

Hormones are released from axon terminals of hypothalamic magnocellular neurons.

Hormones are released into the perivascular space of the sinusoidal capillaries of the pars nervosa.
Describe the vasculature of the posterior pituitary.
The INFERIOR HYPOPHYSEAL ARTERY serves most of the pars nervosa.

Magnocellular neurons of the hypothalamus release oxytocin and ADH directly into the perivascular space of the sinusoidal capillaries of the pars nervosa.

These hormones are then conveyed into the general circulation by the veins that drain the neurohypophysis. Mainly the HYPOPHYSEAL VEINS.
Describe the secretion from the anterior pituitary.
Secretion of regulating hormones (releasing and inhibiting factors) into the HYPOPHYSEAL PORTAL SYSTEM.

Portal vessels deliver regulating factors to the ANTERIOR PITUITARY, where they act on cells to regulate their secretion of the pituitary hormones.

Each type of anterior pituitary cell is controlled by a specific releasing/inhibiting factor.
Describe the vasculature of the anterior pituitary.
The SUPERIOR HYPOPHYSEAL ARTERIES give rise to the PRIMARY capillary plexus, located within the median eminence.

These capillaries reconverge to form the HYPOPHYSEAL VEINS, which descend the talks and penetrate the anterior pituitary and empty into the SECONDARY capillary plexus.

The secondary capillary plexus consists of FENESTRATED capillaries coming off the hypophyseal portal veins in the pars distalis.

Key point: This portal system of veins is how hypothalamic releasing and inhibiting factors reach the anterior pituitary.
Where do hypothalamic neurons secrete into?
The primary capillary plexus within the median eminence of the hypophyseal portal system.
Clinical consideration note: Pituitary adenomas.
Pituitary adenomas are COMMON tumors of the anterior pituitary.

Frequently destroy surrounding bone and neural tissue. Though pituitary adenomas are benign, they can produce problems either from a mass effect (usually visual problems from pressing on the optic chiasm and/or headaches) or from production of hormones such as prolactin or ACTH.

Treated by surgical removal.
Histologically how would you identify a pituitary adenoma?
Need to see a monotonous appearance of cells. So the pituitary doesn't have a great diversity of cells anymore, it just looks uniform.
Clinical consideration note: Tumors of somatotrophs.
Produce excess growth hormone.

Can cause GIGANTISM in children. Abnormally large size from excessive growth of the long bones. Accompanied by muscular weakness and sexual impotence (usually).

Caused by hyperpituitarism before normal ossification is complete.

Can cause ACROMEGALY in adults. Characterized by a gradual and permanent enlargement of the flat bones (as the lower jaw) and of the hands and feet, abdominal organs, nose, lips, and tongue

Develops after ossification is complete.
Make sure you can identify Herring bodies on a zoomed in slide of the posterior pituitary.