Introduction

Question 1

Define the endocrine system

Answer 1

The endocrine system is the collection of glands of an organism that secrete hormones directly into the circulatory system to be carried towards distant target organs

Question 2

Define hormone

Answer 2

A hormone is a regulatory substance produced in an organism and transported in tissue fluids such as blood to stimulate specific cells or tissues into action.

Question 3

Define neurohormone

Answer 3

A neurohormone is a hormone such as vasopressin or noradrenaline produced by nerve cells and secreted into the circulation.

Question 4

List the 6 features of an endocrine hormone

Answer 4

1. Produced by a cell or group of cells
2. Secreted from those cells into the blood
3. Transported via the blood to distant targets
4. Exert their effects at very low concentrations (act in the range 10-9 -10-12 M)
5. Act by binding to receptors on target tissues
6. Have their action terminated, often via negative feedback loops

Question 5

How do we classify endocrine hormones?

Answer 5

Peptide or protein hormones – composed of chains of amino acids (most common), big variation in size from 3 aa to long chains

Steroid hormones – all derived from cholesterol

Amine hormones – all derived from one of two amino acids (tryptophan or tyrosine)

Question 6

How are peptide hormones stored?

Answer 6

Stored in advance - vesicles form containing pro hormone along with proteolytic enzymes that cleave it to form active hormones. Released when triggered and all the contents are expelled into plasma

Question 7

What inactive peptide is linked to insulin as its prohormone form, and what is its clinical significance?

Answer 7

C-peptide
Reflects endogenous insulin production, though levels are roughly 5x higher than blood insulin as insulin is metabolised faster

Question 8

Describe the mechanisms of action of peptide hormones

Answer 8

Water soluble so transported via blood to specific cell surface receptors
Linked to either GPCRs (fast responses) or TK receptors (slow responses)

Question 9

Give some examples of peptide hormones

Answer 9

Insulin
Thyrotropin-releasing hormone (TRH)
Follicle stimulating hormone (FSH)

Question 10

Why are GPCR responses fast and TK responses slow?

Answer 10

G Protein Couple Receptor: Activates 2nd messenger system and/or ion channels leading to modification of existing proteins. Rapid response

Tyrosine Kinase Linked Receptor: Alters gene expression. Slower, longer lasting activity. Second messengers may also alter gene expression. Exception to this is insulin receptor.

Question 11

What type of receptor is the insulin receptor?

Answer 11

Tyrosine kinase receptor

Question 12

Describe steroid hormones

Answer 12

Lipophilic as they are lipids derived from cholesterol. Produced on demand (not released from stores as highly lipophilic and therefore would leak out of vesicles)

Question 13

Describe the transport of steroid hormones to their target sites

Answer 13

Once synthesized they diffuse across the membrane into the ISF and the blood. 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 14

What is the half life of steroid hormones?

Answer 14

60-90 mins

Question 15

What is the half life of amine hormones?

Answer 15

2 mins

Question 16

Where are some steroid hormones produced, giving examples of what these glands produce?

Answer 16

Gonads (testes and ovary) – sex steroids e.g. testosterone, oestrogen and progesterone

Placenta – chorionic gonadotropin (hCG, pregnancy tests), sex steroids

Kidney - Vitamin D3

Adrenal cortex - corticosteriods

Question 17

What are all steroid hormones derived from?

Answer 17

Cholesterol

Question 18

Describe the mechanism of action of steroid hormones

Answer 18

Lipophilic so once transported to the site of action can diffuse over cell membrane to either cytoplasmic or nuclear receptors to alter gene expression (causes lag time for response, hours to days)

Some evidence they can bind cell surface receptors for rapid responses

Question 19

Describe the formation of amine hormones

Answer 19

Most amine hormones are derived from tyrosine

All but one, melatonin, which is derived from tryptophan

Question 20

What are the two classes of amine hormone, and how do they differ in their mechanisms of action?

Answer 20

Catecholamines - similar to peptide hormones, hydrophilic e.g. dopamine, norepinephrine (neurons) and epinephrine (adrenal medulla)
Thyroid hormones - similar to steroid hormones, lipophilic e.g. triiodothyronine (T3) and thyroxine/thyroid hormone (T4)

Question 21

Describe the law of mass action in terms of hydrophobic amine hormones

Answer 21

The Law of Mass Action dictates that as free hormone leaves the plasma (taken up by cells), more of the hormone is released from the carriers. Typically only minute quantities of hormone are required for physiological functions.

Question 22

Why must the bound:unbound ratio of amine hormones be maintained?

Answer 22

As hormone is taken up, more is released from carrier. This allows for a reservoir of hormone ready for action for prolonged activity

Question 23

Which hormones have short half lives in plasma (around minutes) and why?

Answer 23

Peptide hormones
Catecholamines from amine hormones

Hydrophilic, prone to degradation before reaching target, require continued secretion for prolonged action. Also are excreted rapidly

Question 24

What hormones have long half lives in plasma and why?

Answer 24

Steroid hormones
Thyroid hormones from amine hormones

Are lipophilic, so circulate in plasma bound to specific transport plasma proteins (eg thryoxine-binding globulin, or albumin) so have longer half-life in plasma, usually hours to days. Also alter protein synthesis via modifying gene expression thus effect also persists for hours to days e.g. anti-inflammatory steroids switch of the production of inflammatory proteins. Also are slowly excreted as they are bound.

Question 25

How are hormones removed?

Answer 25

Excretion by kidneys into urine

Metabolised by the liver

Question 26

How is hormone secretion regulated?

Answer 26

Negative feedback loops (by physiological response or product, short loop vs long loop)
Neural feedback loop

Question 27

What is growth hormones affect on insulin receptor expression?

Answer 27

GH causes down regulation of insulin receptors (those with acromegaly can present with suspected diabetes)

Question 28

What is a permissive effect?

Answer 28

Permissive effect refers to the presence of one hormone enhancing the effect of another e.g. epinephrine causes only modest lipolysis in adipose tissue, but when thyroid hormones are also present, greatly increased lipolysis occurs.

Question 29

How many people in Scotland have diabetes?

Answer 29

1 in 20

Question 30

What % of inpatients have diabetes?

Answer 30

15-20%

Question 31

What % of total inpatient expenditure is spent on patients with diabetes?

Answer 31

12%