Introduction to endocrine

Question 1

Define what the endocrine system is

Answer 1

A system that integrates and controls organ function via the secretion of chemicals (hormones) from cells, tissues or glands…

…which are then carried in the blood to target organs, distal from the site of hormone synthesis, where they influence the activity of that target organ

Question 2

In a basic sense, what are the differences between the following:

a) endocrine
b) paracrine
c) autocrine
d) exocrine

Answer 2

Endocrine - hormones released into blood

Paracrine - act locally to the site of synthesis/secretion (eg histamine)

Autocrine - acts on the same cell that produced/secreted it (eg cytokines)

Exocrine - secreted to outside environment via ducts

Question 3

In order for endocrine communication to happen, there must be _________ on the cells of the target tissue

Answer 3

Receptors

Tissues detect hormones through the presence of specific receptors for that chemical on/in the cells. No receptor = no response

Question 4

How does neuroendocrine communication work?

Answer 4

Nerves release hormones which enter blood and travel to their target cells e.g. hypothalamic – posterior pituitary axis.

Question 5

What are the different types of endocrine hormones?

What are they derived from/made from?

Answer 5

Peptide or protein hormones (most common) - amino acid chains

Amine hormones - derived from tyrosine or tryptophan

Steroid hormones - all derived from cholesterol

Question 6

How are peptide hormones produced?

Answer 6

Synthesised in cells as preprohormone in advance of need then cleaved into prohormone and stored in vesicles until required

Question 7

Describe what happens in stage (1)

Answer 7

Preprohormone polypeptide synthesised from mRNA strand

The chain contains a ‘signal sequence’ of amino acids - which causes it to be directed into the ER’s lumen

Question 8

What happens at stage (2)

Answer 8

Enzymes in the Endoplasmic reticulum chop off the signal sequences from the preprohormone to make a prohormone (still inactive)

The prohormone is then packaged into a transport vesicle and moves towards to golgi

Question 9

What happens at stage (3)

Answer 9

the prohormone moves through the golgi complex and passed out the other end in a secretory vesicle

Question 10

What happens in stage (4)?

Answer 10

Secretory vesicles bud off the golgi complex

These contain the prohormone and enzymes - which chop the prohormone into 1 or more active peptides (+ fragments)

Question 11

What happens in stage 5 & 6?

Answer 11

Secretory vesicle releases its contents into ECF through exocytosis. This is called co-secretion - as both hormone and fragments are yeeted out.

The hormone then moves from the ECF to the blood to be transported to its target

Question 12

Co-secretion involves the secretion of hormones alongside their inactive fragments.

Give an example of how measuring the levels of these inactive fragments be clinically useful

Answer 12

C-peptide levels can be measured for diabetic patients

(measuring insulin levels does not differentiate between endogenous and synthetic insulin)

Question 13

How do peptide hormones travel around the body?

Answer 13

Peptide hormones are water-soluble (hydrophilic) so dissolve in plasma but not across membranes.

This means receptors for peptide hormones are on target cell membranes, not intracellular

Question 14

How long does it take peptide hormones to produce a biological response?

Answer 14

Generally fast-acting - (seconds to minutes)

Question 15

What signalling pathways are peptide hormones typically involved with?

Answer 15

Most peptide hormones work via modulating either GPCR or tyrosine kinase linked signalling pathways

These pathways phosphorylate existing proteins in the cell and modify their function e.g. open or close ion channels, activate or inactivate enzymes

Question 16

What is the GCPR signalling pathway?

Answer 16

G-coupled protein receptors - found on membrane

Hormone binding activates 2nd messenger system and/or ion channels leading to modification of existing proteins.

Rapid response

Question 17

What is the effect of hormones binding to Tyrosine kinase linked signalling pathways?

Answer 17

Alters gene expression - (although GCPR 2nd messengers can do this)

Slower, longer lasting activity

Question 18

What are amine hormones?

Answer 18

Hormones derived from amino acid Tyrosine - apart from melatonin which is derived from tryptophan

Examples - Dopamine, Norepinephrine (NA), Epinephrine (adrenaline), Thyroxine, Triiodothyronine

Question 19

The amine hormones derived from tyrosine can be split into two groups.

What are these groups?

Answer 19

Catecholamines & Thyroid hormones

Catecholamines - Dopamine, Adrenaline, NA:

• Hydrophilic
• Similar mechanisms of action to peptide hormones

Thyroid hormones - Thyroxine, Triiodothyronine:

• ​Lipophilic
• Similar mechanisms of action to Steroid hormones.

Question 20

What are steroid hormones derived from?

Answer 20

Hormones derived from cholesterol

Question 21

How are steroid hormones stored?

Answer 21

Steroid hormones arent really stored - they are synthesised directly when needed

This is because they are lipophilic so just diffuse across membranes (cant be contained) into the ISF, blood

Question 22

How are steroid hormones transported around the body?

Answer 22

Being poorly soluble in water - they are transported bound to carrier proteins such as albumin.

This stabilises their transport through the plasma and protects them from enzymatic degradation, phenomenally increasing their half life (60-90mins vs 2mins for amine hormones).

Question 23

What organs/tissues produce steroid hormones?

Answer 23

Gonads (testes/ovaries) - Sex steroids

Placenta - Human Chorionic gonadotropin (hCG), sex steroids

Kidney - vitamin D3

Adrenal cortex - corticosteroids (cortisol, aldosterone)

Question 24

What determines what steroid hormone is produced from cholesterol?

Answer 24

Depends on what cell (what tissue) is doing the altering - gonad cells will do different stuff than kidney etc

Question 25

Where are receptors for steroid hormones located?

Answer 25

Intracellularly - either cytoplasmic or nuclear

Activation will cause activation or repression of gene function within that cell (genomic effect) - leading to increased/decreased synthesis of specific proteins

This takes a while compared to the other hormone types

Question 26

Hello, this diagram is of how steroid hormones work. Describe what happens at each stage

Answer 26

Question 27

When talking about lipophilic hormones such as steroid hormones - we need to know what ‘free hormones’ are

What does this mean?

Answer 27

Lipophilic hormones are mainly transported in plasma bound to transport proteins - such as albumin

However - a small portion of the steroid hormones remain unbound (free)

The ratio of free to complexed steroid hormone is usually very small. The extent of protein binding can have important effects on the hormone’s actions

Question 28

In your plasma, most steroid hormones are complexed with albumin and a small amount is not

What happens when the free steroid hormones are taken up by cells?

Answer 28

Law of mass action states that when free hormone leaves the plasma - that more hormone is released by the carriers

Thus the concentration of free hormone remains the same (ish)

Question 29

Give examples of the carrier proteins used to transport lipophilic hormones such as steroids or thyroid hormones

Answer 29

Some specific transporters:

• corticosteroid-binding globulin

Non-specific (carry lots of different ones):

• Albumin

Question 30

What are the benefits of using transporter proteins to transport lipophilic hormones?

Answer 30

Increases solubility –> required for blood-mediated transport

Protects from degradation –> increased half life (> 60 min)

Question 31

In most endocrine pathways, secretion is responsive to _______ _______ reflexes

Answer 31

In most endocrine pathways, secretion is responsive to negative feedback reflexes

An example of this is parathyroid hormone - its release stimulates increased plasma [Ca²⁺], but increased [Ca²⁺] inhibits the release of parathyroid hormone

Question 32

Why are single measurements of hormone levels in a patients blood not very useful in many ways?

Answer 32

Hormones tend to be released in short bursts - thus [hormone] varies widely depending on the environment, time etc

Clinical relevance is that single values of [hormone] may be misleading