Intro to endocrinology

Question 1

What are the 3 groups hormones are classified under?

Answer 1

1. Protein/Polypeptide hormones
2. Steroid hormones
3. Miscellaneous hormones

Question 2

What is an example of a protein/polypeptide hormone and where is it produced?

Answer 2

Adrenocorticotropic Hormone (ACTH)
- Produced at the anterior pituitary

Question 3

What is the basic concept in the synthesis of protein/polypeptide hormones?

Answer 3

Produced as inactive prohormones and then cleaved to give the hormone

Question 4

What is the prohormone of ACTH?

Answer 4

Pro-opiomelanocortin (POMC)

Question 5

What are all anterior pituitary hormones?

Answer 5

Polypeptides

Question 6

How are protein/polypeptide hormones synthesised?

Answer 6

1. Use blood supply –> provides amino acids
2. DNA transcribed to form Prohormone
3. mRNA moves into cytoplasm –> binds to rER
4. Prohormone endocytosed into golgi apparatus
5. Golgi adds enzymes to vesicles containing pro-hormone
6. Enzymes cleave prohormone which leads to the making of active hormone.
7. protein hormone always stored in secretory granules
8. When signal arrives –> exocytosis –> ACTH released into blood

Question 7

What are all steroid hormones derived from?

Answer 7

Cholesterol

Question 8

How is cholesterol stored in cells and what do they look like in the cell?

Answer 8

Cholesterol is delivered in the form of LDLs.

The cholesterol is stored as Fatty Acid Esters which appear as fat droplets

Question 9

Where are most steroid hormones produced?

What enzyme breaks down fatty acid esters?

Answer 9

Adrenal Glands or Gonads.

Esterase

Question 10

Where does steroid hormone synthesis take place within the cell?

Answer 10

Mitochondria

Question 11

How does cholesterol get into the mitochondrion and what is this step called?

Answer 11

Via StAR proteins (steroidogenic acute regulatory proteins)

• One of the rate limiting steps in steroid hormone production
• More StAR proteins = more cholesterol into mitochondria = more steroid hormone produced

Question 12

How are steroid hormones synthesised?

Answer 12

1. Cholesterol delivered to cell in form of LDLs
2. Stored in cell as Fatty Acid Esters + appear as fat droplets
3. Esterase enzymes break down fatty acid esters to liberate cholesterol
4. Cholesterol gets into mitochondrion via StAR proteins
5. When cholesterol enters the mitochondrion, there are lots of enzymes that allows the step-wise conversion of cholesterol into steroid hormone of choice e.g. cortisol
6. Which is then secreted into cytoplasm from the mitochondrion

Question 13

As all steroid hormones are derived from cholesterol, what determines the final hormone produced?

Answer 13

The combination of enzymes that are found within the cell

Question 14

In terms of secretion, how are steroid hormones and peptide hormones different?

Answer 14

• Steroid hormones = secreted immediately into the blood as they are produced becuase they are very lipid soluble
• Protein/Polypeptide hormones = packaged into vesicles and remain by the cell surface awaiting a signal before they are exocytosed.

Question 15

State some key features of protein/polypeptide hormones and state how they are stored.

Answer 15

Protein/polypeptide hormones:

• secreted into the blood and travel unbound to site of action
• are stored in the tissues that produce them
• have a very short half-life (matter of minutes)
• are not bound to any plasma proteins in the blood so sensitive to enzymatic break down

Question 16

How are steroid hormones transported/stored?

Answer 16

• Stored in the blood
• Bound to carrier proteins such as albumin (interaction with this is not specific) or other specific carriers such as cortisol and corticosteroid binding globulin.

Question 17

Are all steroid hormones bound to plasma proteins in the blood?

Answer 17

• Vast majority are - does not leave the bloodstream

- Small amount of free steroid hormone in the blood - only this can move into the tissues

Question 18

State 3 ways in which the steroid hormone equilibrium in the blood can be shifted. Give examples

Answer 18

1. Uptake of steroid hormones by tissue
2. Rise in plasma protein levels.
   - More plasma proteins = more likely that the plasma proteins will bind to the hormone = more protein bound hormone formed
3. Cortisol is a stress hormone and in times of stress, more of the free cortisol enters the tissues so the free cortisol levels fall. In pregnancy more plasma proteins are synthesised.

Question 19

Describe the mechanism of action of ACTH in stimulating cortisol production.

Answer 19

1. ACTH receptors are usually G-protein coupled receptors.
2. Binding of ACTH to the ACTH receptor activates adenylate cyclase, which converts ATP to cAMP.
3. The increase in cAMP activates Protein Kinase A.
4. Esterase is phosphorylated, and so cholesterol is liberated.
5. Phosphorylation of the StAR protein activates the StAR protein allowing cholesterol to move into the mitochondrion.
6. This then stimulates steroid hormone production.

Question 20

What type of receptor do steroid hormones bind to?

Answer 20

Intracellular receptors - once steroid hormone binds to the receptor, they translocate to the nucleus and act as transcription factors

Question 21

Describe the negative feedback loop of ACTH and cortisol.

Answer 21

1. The anterior pituitary is stimulated by stress
2. ACTH is released
3. ACTH acts on the adrenal gland to increase cortisol production.
4. Cortisol enters the bloodstream and carries out its function to decrease stress
5. Cortisol returns to the anterior pituitary and switches off cortisol production.

Question 22

When can you get a positive feedback loop?

Answer 22

With LH and Oestrogen.