Principles of Endocrinology

Question 1

What is an endocrine gland?

Answer 1

A group of cells which secrete ‘messenger’ molecules directly into the bloodstream.

Question 2

What is a hormone?

Answer 2

The bioactive ‘messenger’ molecule secreted by an endocrine gland into the blood i.e. not simply a metabolite or energy substrate.

Question 3

What is endocrine?

Answer 3

Relates to hormone’s action on target cells AT A DISTNACE from source.

Question 4

What is paracrine?

Answer 4

Relates to hormone’s action ON NEARBY TARGET CELLS e.g. within immediate area around source.

Question 5

What is autocrine?

Answer 5

Relates to hormone having an effect ON ITS OWN IMMEDIATE SOURCE (self).

Question 6

What are the three hormone classifications?

Answer 6

Protein/polypeptide hormones Steroid hormones Miscellaneous

Question 7

What is a protein/polypeptide hormone?

Answer 7

Made of amino acids. Many are originally produced as precursors (called prohormones). They are cleaved by enzymes to produce to active hormone.

Question 8

Example of protein hormone?

Answer 8

ACTH (from POMC)

Question 9

What is a steroid hormone?

Answer 9

Synthesis of steroid hormones begins with cholesterol – this is the precursor. All hormones therefore have cholesterol backbones.

Question 10

Example of steroid hormone?

Answer 10

Cortisol

Question 11

How are protein hormones synthesised and released into bloodstream?

Answer 11

1. Transcription of mRNA of the protein hormone is initiated by a chemical signal. 2. Amino acids transported into cell. 3. Specific mRNA is translated to prohormone in the RER using the amino acids. 4. Transformed to the active hormone by the Golgi apparatus – Golgi packages prohormone with proteolytic enzymes which generate mature active hormone. 5. Vesicle that contains hormone brought to edge of cell and released into CAPILLARY by exocytosis when a signal comes along.

Question 12

How are steroid hormones synthesised and released into bloodstream?

Answer 12

1. LDL, a source of cholesterol is transported into cells by receptors – endocytosis. 2. Cholesterol is removed from LDL and stored as fatty acid esters in cytoplasmic vacuoles, through esterification. 3. When you want to make the hormone, esterase liberates cholesterol from the esters, and StAR protein drives it into the mitochondria where the enzymes for hormone synthesis are found. This process is the rate limiting step. 4. Mature hormone is produced. Steroid hormone is fat soluble so not stored and perfuses across membrane into capillaries by simple diffusion.

Question 13

What does cholesterol backbone look like?

Answer 13

Ignore the CH2/CH3 tail.

Question 14

What are the differences between protein and steroid hormones in how they operate? (x2)

Answer 14

Protein hormones are stored within cells. Once proteins are secreted into the blood, their actions are very short-lived. Steroid hormones are stored in the blood stream by binding to certain plasma proteins. Effects are very long-lasting (explanation later).

Question 15

What are the two ways steroid hormones are stored? (x2)

Answer 15

Albumin can weakly bind many steroid hormones. More importantly, there are specific binding proteins for most steroid hormones e.g. cortisol – cortisol-steroid binding globulin (CBG). These bind with high affinity.

Question 16

Describe the nature of blood and the proportions of stored steroid hormones. How are they stored in the blood?

Answer 16

Vast majority of steroid hormone is bound to plasma proteins. Stored because it cannot get out of the blood. There’s always a SMALL pool of free steroid hormone – this is the active hormone that can move in and out of cells. Therefore, there is a dynamic equilibrium therefore set up – Hormone + Plasma Protein –> Protein Bound Hormone.

Question 17

Describe the nature of blood and the proportions of stored steroid hormones. How are they stored?

Answer 17

Vast majority of steroid hormone is bound to plasma proteins. Stored because it cannot get out of the blood. There’s always a SMALL pool of free steroid hormone – this is the active hormone that can move in and out of cells. Therefore, there is a dynamic equilibrium therefore set up – Hormone + Plasma Protein –> Protein Bound Hormone.

Question 18

How can proportions of plasma protein and free steroid hormone be adjusted? (x3) Why is it important?

Answer 18

Adjustment of secretion rates of the hormone. When steroid hormone gets into cell and removed from blood stream (equilibrium adjusted to restore free hormone levels). When plasma protein concentration is altered. Ensures that free hormone available to the tissues remains CONSTANT.

Question 19

What example would plasma protein concentration would change?

Answer 19

Pregnancy results in increased CBG levels and therefore, cortisol levels rise to ensure constant level of free hormone available to tissues.

Question 20

If a steroid hormone is heavily plasma protein bound, can it still access tissues?

Answer 20

YES – this question is obviously trying to catch you out. Will always be some free hormone, even if the hormone that is bound is bound heavily.

Question 21

Where does ACTH act?

Answer 21

Adrenal cortical cell. Adrenal cortex!

Question 22

What is the mechanism of ACTH interaction with its target cell i.e. how does it bring about its response? What is this response?

Answer 22

THIS IS GENERAL FOR PROTEIN HORMONES. 1. ACTH binds to the Gs-protein coupled receptor. 2. Leads to dissociation of alpha subunit of Gs protein from beta and gamma subunits. 3. Leads to activation of adenylate cyclase which converts ATP to cAMP. 4. cAMP binds to cAMP dependent Protein Kinases. 5. Protein Kinases activates cholesterol esterase which converts cholesterol esters to free cholesterol AND activates StAR protein which mediates transfer of cholesterol inside mitochondria. NB: I know we refer to cholesterol as the process it stimulates, but remember that the stimulus is our ACTH. LOOK AT CELL SIGNALLING IN TISSUES IN MCD FOR GREATER DETAIL ON ACTIVATION!!!!!!!!!

Question 23

What is the mechanism of cortisol interaction with its target cell and how does it bring about a response?

Answer 23

THIS IS GENERAL FOR STEROID HORMONES. 1. Free cortisol enters target cell by simple diffusion because are lipid soluble. 2. Receptors are found intracellularly because of this. Cortisol binds to Glucocorticoid receptors in cell cytoplasm. 3. This hormone-receptor complex translocates to the nucleus where it binds to specific DNA binding sites. 4. There, it can upregulate/downregulate transcription.

Question 24

Why are steroid hormones considered very powerful?

Answer 24

Because they influence transcription rates and production of mRNA. So profound effects on cell function. Long-lasting too because transcription takes a while for effects to fabricate. SLOW PROCESS.

Question 25

NEED TO LOOK AT DIFFERENT RECEPTORS (ONLY HOW THEY WORK and very briefly the intracellular mechanisms hormones induce for ones I have not covered.)

Answer 25

Found in MCD: Tissues – Cell signalling.

Question 26

Give an example with hormones already discussed how a negative feedback system works.

Answer 26

Most endocrine systems operate in a negative feedback loop. e.g. You are stressed: Activate the anterior pituitary gland to produce ACTH. This protein polypeptide hormone is secreted to activate the adrenal gland to produce cortisol – this is your stress hormone which is what you need. Cortisol has effects on cells, but also has an effect on the cell responsible for produced ACTH in the pituitary, switching off its function. This is negative feedback system.

Question 27

Why is negative feedback system important in endocrinology?

Answer 27

Negative feedback system regulates the body’s exposure to hormones.