Introduction to Endocrinology

Question 1

Name the 3 ways hormones can be classified?

Answer 1

1. Protein/polypeptide hormones
2. Steroid hormones
3. Miscellaneous-Thyriod hormones because they have iodine in their structure

Question 2

What are steriod hormones derived from?

Answer 2

Derived from cholesterol

Question 3

List the steps for hormone synthesis?

EXAMPLE: Adrenocorticotropic Hormone (ACTH)

Prohormone of ACTH: Pro-opiomelanocortin (POMC)

Also draw a diagram

Answer 3

• Specific mRNA sythesized within cell nucleus
• Translation of specific mRNA to prohormone,POMC, in rough ER
• Prohormone transported to Golgi apparatus where processed by proteolytic enzymes to mature, active hormone (these hormones are located within the vesicles)
• By the time the vesicle has reached the plasma memebrane, the proteolytic enzyme has activated the enzyme
• Cleavage of the pro-hormone leads to generation of the active hormone
• Vesicles filled with active hormone (e.g. ACTH) accumulate near the cell surface - when a signal arrives, you get exocytosis and the ACTH is released into the blood

Question 4

Which blood vessels are pituitary hormones secreted into?

Answer 4

Pituitary capillary

Question 5

In which cell is Cortisol produced?

Answer 5

adrenal cortical cell

Question 6

List the steps for Hormone Synthesis?

Answer 6

• LDL rich in cholesterol transferred into cell by endocytosis and are stored as Fatty Acid Esters (seen as fat droplets).
• To synthesise steroid hormones you need to break down the fatty acid esters to liberate cholesterol
• Esterase enzymes break down the fatty acid esters
• The cholesterol molecule is carried into the mitachondria using the StAR protein.

STEROID HORMONES ARE MADE IN THE MITOCHONDRIA

This is one of the rate limiting steps in steroid hormone production

The more StAR proteins you have, the more cholesterol you can get into the mitochondrion and the more steroid hormone you can produce

When cholesterol enters the mitochondrion, there are lots of enzymes that allows the step-wise conversion of the cholesterol into the steroid hormone of choice

The enzymes present in certain cells determines the final steroid hormone product (e.g. adrenal cortical cells have a set of enzymes that produced cortisol

• once mature hormone produced, it can freely diffuse across the cell membrane into the circulation

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Question 7

What is the role of esterase?

Answer 7

Breaks down fatty acids and liberates cholesterol

Question 8

What does the StAR protein do?

Answer 8

Carries cholesterol into the mitachondria

Question 9

Where are steriod hormones mostly stored?

Answer 9

In the blood, proteins like albumin bind to hormones. There are also specific binding globulins (i.e. CBG).

Write a question about their function

Question 10

What is the DIFFERENCE BETWEEN POLYPEPTIDE HORMONE AND STEROID HORMONE SECRETION:

Answer 10

Protein/polypeptide hormones are stored in vesicles in the cell, awaiting a stimulus triggering exocytosis

Steroid hormones are secreted into the blood stream as soon as they are produced - they’re very lipid soluble

Question 11

How are protein hormones transported in the blood ?

Answer 11

Protein/polypeptide hormones are secreted into the blood and travel UNBOUND to the site of action

Question 12

Why do protein hormones have very short half lives?

Answer 12

Protein/polypeptide hormones are secreted into the blood and travel UNBOUND to the site of action

Protein/polypeptide hormones, as a result, have VERY SHORT HALF LIFES

They aren’t bound to any plasma proteins in the blood so they are sensitive to enzymatic break down

Half life is usually a matter of minutes

Question 13

How are steriod hormones transported in the blood?

Talk about all the different ways it is transported in the blood.

Answer 13

Stored in the BLOOD

They bind to a number of plasma proteins

Albumin - present in large amount in the plasma - it can mop up a large amount of most steroid hormones but the interaction isn’t very specific

For each individual steroid hormone there tends to be a fairly specific plasma protein which forms a much stronger binding (e.g. Cortisol - Corticosteroid Binding Globulin (CBG))

The vast majority of steroid hormone will be bound to plasma proteins in the blood

There is a small amount of free steroid hormone in the blood

Question 14

What is the difference between steriod hormones unbound by a plasma protein or bound to a plasma protein?

Answer 14

NOTE: If the steroid hormone is bound to a plasma protein then it is not leaving the blood stream - only free steroid hormone can move into the tissues

Question 15

Write down the equilibrium for plasma protein, hormone and protein bound hormone

Answer 15

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Question 16

Referring to the steriod hormone equilibrium.

What will happen if you have an uptake of steriod hormone by the tissue?

Answer 16

EXAMPLE: Cortisol is a stress hormone.

At times of stress, more of the free cortisol enters the tissues and the concentration of free cortisol begins to fall.

Some of the protein bound hormone releases to try and maintain the free steroid hormone levels in the blood

If the tissues start to use up more steroid hormone - it stimulates the endocrine cells to produce more of the steroid hormone

Question 17

Referring to the steriod hormone equilibrium.

What will happen if you have a rise in plasma protein level?

Answer 17

The more plasma proteins you have, the more likely it is that the plasma proteins are going to bind to steroid hormone and so more protein bound hormone is formed.

The equilibrium is maintained.

EXAMPLE: Pregnancy - plasma proteins that bind to cortisol

Plasma proteins that bind to cortisol rise massively during pregnancy

This sends a message to the endocrine cells to increase steroid hormone synthesis

This maintains the level of free cholesterol in the blood

Anything that shifts the equilibrium will stimulate the endocrine cells to produce more steroid hormone.

Question 18

What is the mechanism of action for a peptide hormone.

Use ACTH as an example

Answer 18

Protein/polypeptide hormones aren’t generally lipid soluble so you need a protein receptor to recognise the hormone - ACTH Receptor (in the adrenal gland)

The receptors are usually G-protein coupled receptors

Binding of ACTH to the ACTH receptor activates Adenylate Cyclase which causes an increase in cAMP production from ATP

Increase in cAMP activates Protein Kinase A

Esterase is phosphorylated which liberates cholesterol

In addition, the phosphorylation of StAR Protein activates the StAR Protein - allowing cholesterol to move into the mitochondrion

This stimulates steroid hormone production

The protein/polypeptide hormone ACTH influences the production of steroid hormone cortisol

Question 19

What is the mechanism of action for a steriod hormone.

Answer 19

Only free steroid hormones can get into cells

They are very lipid soluble so can diffuse through the membrane

Steroid Hormones bind to INTRACELLULAR RECEPTORS

Once bound to the receptor, they translocate to the nucleus and have a massive effect on DNA Transcription and subsequent translation

Steroid hormone have a massive effect by changing the protein machinery within the cell

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Question 20

What is the mechanism of action for a peptide hormone.

Use cortisol as an example

Answer 20

Free Cortisol enters cell by passive diffusion

Binds to specific Glucocorticoid (GC) receptors in cell cytoplasm

This hormone-receptor complex travels to nucleus & binds to specific DNA binding sites

Leads to changes in transcription rates of specific genes and production of mRNA

Translation of mRNA to protein within endoplasmic reticulum

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Question 21

State the negtative feedback mechanism for cortisol.

Start of with ACTH

Answer 21

Anterior pituitary is stimulated by stress

Protein/polypeptide hormone ACTH is released

ACTH acts on the adrenal gland to increase cortisol production

Cortisol enters the bloodstream and carries out its function to decrease stress

Cortisol returns to the anterior pituitary and switches ACTH off (end consequence is that Cortisol production is also switched off)