Diabetes & Endocrinology Welcome - Introduction and Case Launch

Question 1

what is the defintion of the endocrine system?

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

how fast may the response from the endocrine system be?

Answer 2

Response may be fast (within seconds) e.g. increased heart rate in response to adrenalin, or slow (over days) e.g. increased protein synthesis in response to growth hormone

Question 3

Endocrine hormones should not be confused with:

paracrine chemicals - what are they?

Answer 3

act local to the site of synthesis, do not travel to distant sites e.g. histamine

Question 4

Endocrine hormones should not be confused with:

autocrine chemicals - what are they?

Answer 4

act on/in the same cell that synthesises the hormone e.g. cytokines

Question 5

Endocrine hormones should not be confused with:

exocrine chemicals - what are they?

Answer 5

released from exocrine glands via ducts to the external environment including the GI tract e.g. saliva, sweat, bile

Question 6

The endocrine system, together with the ___________, communicates with and controls all body functions

Answer 6

The endocrine system, together with the nervous system, communicates with and controls all body functions

Question 7

How do endocrine hormones communicate with their target organs/tissues?

Answer 7

Hormones travel in the blood to their target organs/tissues

Tissues detect hormones through the presence of specific receptors for that chemical on/in the cells

No receptor = no response

Question 8

what is neural communication?

Answer 8

Neurotransmitters released from presynaptic neurons travel across the synaptic cleft to the postsynaptic cell to influence its activity. Neurotransmitter is the chemical released by the neuron but, in contrast to hormones, acts locally within the synaptic cleft.

The endocrine and nervous systems co-operate intimately to provide further control, particularly for long-term phenomena, e.g. growth.

Question 9

what is neuroendocrine communication?

Answer 9

endocrine and nervous systems combine

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

Question 10

Is the response to a hormones specific?

Answer 10

Although all hormones circulate throughout the body in the blood, the response to any one hormone is highly specific because only target cells have receptors for the hormone

Question 11

Can the same hormone have different effects in different target cells?

Answer 11

While the response of a target cell to any one hormone is highly specific, the same hormone can have different effects in different target cells. For example: Insulin

When insulin binds to receptors on skeletal muscle of adipose tissue, they take up glucose from the blood

When it binds to the liver - causes liver to convert glucose into glycogen for storage – glycogenesis

Also causes decreased production of new glucose as don’t want any more - gluconeogenesis

Question 12

what is the difference between autocirne and paracrine

Answer 12

Question 13

what is the function of hormones?

Answer 13

The function of hormones (and NTs) is to bring about changes in the activity of their target cells and tissues, (increase/decrease a particular activity)

Endocrine function is embedded in a number of physiological systems (reproductive, renal, gastrointestinal) as well as being a diffuse system of glands in it’s own right (thyroid gland, adrenal gland, pituitary gland, hypothalamus)

Question 14

is the endocrine system continuous?

Answer 14

The endocrine system is not anatomically continuous, but the various glands do form individual functional systems

Question 15

what are examples of endocrine glands?

(slides 11 and 12 summary of all endocrine glands - useful)

Answer 15

the hypothalamus and the pituitary, thyroid and parathyroid glands as well as

the pancreas and the adrenal glands (above the kidneys) as well as the kidneys themselves. You have already covered the GIT in GI block, and will study the ovary and testis in the Reproduction block (Yr 3).

Question 16

what are the features of an endocrine hormone?

Answer 16

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 17

what are the different classifications of endocrine hormones?

Answer 17

1. Peptide or protein hormones
2. Amine hormones
3. Steroid hormones

Question 18

what are peptide or protein hormones?

Answer 18

composed of chains of amino acids (most common)

may be small or large

Question 19

what are amine hormones?

Answer 19

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

Melatonin made by the pineal gland is the only one made from tryptophan and rest are made from tyrosine

Question 20

what are steroid hormones?

Answer 20

all derived from cholesterol

Question 21

what are peptide hormones made as before they are needed?

Answer 21

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

First made as preprohormones by the ribosomes and contains a signal sequence and then moves into the endoplasmic reticulum. May contains multiple copies separated by other peptide fragments separating the activate parts of the peptide hormones. Once signal sequence has moved it into the endoplasmic reticulum a prohormone is made then it moves into the golgi complex then the prohormones is packaged into vesicles with proteolytic enzymes and the prohormone is chopped up into active fragments

Vesicles stored until it is needed

Vesicles have hormone and enzymes in them

Question 22

what are preprohormones and where are they made?

Answer 22

The initial peptide hormone produced by ribosomes is large and inactive - preprohormone

Preprohormones contain one or more copies of the active hormone in their amino acid sequence

Question 23

Where are prehormones cleaved into smaller units and what does this produce?

Answer 23

Preprohormones are cleaved into smaller units in the endoplasmic reticulum to leave smaller but still inactive proteins called prohormones

Question 24

What and where are prohormones packed in?

Answer 24

Prohormones are packaged into vesicles in the golgi apparatus, along with proteolytic enzymes which break the prohormone down into active hormone and other fragments

Question 25

Where are hormones and fragments stored until they are needed?

Answer 25

Hormones and fragments are stored in vesicles in the endocrine cells until release is triggered then all vesicle contents are released into plasma (co-secretion)

Question 26

what is C-peptide and what is it useful for?

Answer 26

C-peptide is the inactive fragment cleaved from the insulin prohormone

Levels of C-peptide in plasma or urine are often measured to indicate endogenous insulin production from the pancreas (produced in equal amounts)

However, because insulin is metabolised faster, levels of C-peptide are typically about 5x higher than endogenous insulin

Measuring inactive fragments in plasma can be useful clinically e.g. C-peptide in diabetes

Question 27

why measure C-peptide and not insulin directly?

Answer 27

Insulin that is produced is metabolised quickly and c peptide hangs around for longer

If patient is type 1 diabetic, want to stabilise blood levels quickly

You don’t know whether you are measuring the patients own insulin or whether it’s the insulin they are taking so measure C-peptide and this tells you the levels of insulin made by the patients own pancreas

Question 28

what is the process of peptide hormones being made?

Answer 28

The initial peptide hormone produced by ribosomes is large and inactive - preprohormone. Preprohormones contain one or more copies of the active hormone in their amino acid sequence

Preprohormones are cleaved into smaller units in the endoplasmic reticulum to leave smaller but still inactive proteins called prohormones

Prohormones are packaged into vesicles in the golgi apparatus, along with proteolytic enzymes which break the prohormone down into active hormone and other fragments

Hormones and fragments are stored in vesicles in the endocrine cells until release is triggered then all vesicle contents are released into plasma (co-secretion)

Measuring inactive fragments in plasma can be useful clinically e.g. C-peptide in diabetes

Question 29

are peptide hormones water soluble and what does this mean?

Answer 29

Water soluble so dissolve easily in plasma making transport via the blood simple and easy

Water solubility however means cannot cross cell membrane so bind to membrane bound receptors on target cell

Question 30

what happens when peptide hormones binds to membrane bound receptors on the target cell?

Answer 30

Once bound these receptors generally create relatively fast biological responses (seconds to minutes)

Most peptide hormones work via modulating either the 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 31

Peptide hormones work by activating what on signalling pathways and how do these work?

Answer 31

Most peptide hormones work via modulating either the 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 32

where do peptide hormones bind to receptors?

Answer 32

They are Hydrophillic/lipophobic = Binds to a cell surface receptor

(water loving and lipid hating)

Question 33

what is the process of peptide hormones activating G protein coupled receptors?

Answer 33

Activates 2nd messenger system and/or ion channels leading to modification of existing proteins. Rapid response

G proteins can also directly act on ion channels and change ion conduction

Question 34

what is the process of peptide hormones activating tyrosine kinase linked receptors?

Answer 34

Alters gene expression

Slower, longer lasting activity

Question 35

what are amine hormones derived from?

Answer 35

Most are derived from the amino acid tyrosine

Only amine hormone not derived from tyrosine is melatonin which is derived from tryptophan. Melatonin regulates circadian rhythm

Question 36

What different type of hormones can tyrosine make?

Answer 36

catecholamines

thyroid hormones

Question 37

What are different catecholamines made from tyrosine? and what is their mechanism of action like?

Answer 37

Dopamine (CNS neurotransmitter)

Norepinephrine (neurotransmitter)

Epinephrine (hormone released by adrenal medulla)

Similar mechanism of action to peptide hormones (hydrophilic)

Question 38

What are different thyroid hormones made from tyrosine? and what is their mechanism of action like?

Answer 38

Similar mechanism of action to steroid hormones (lipophilic)

Question 39

what are steroid hormones?

Answer 39

lipids derived from cholesterol

Question 40

Are steroid hormones made before they are needed?

Answer 40

Unlike the other types of hormones, steroid hormones are synthesized directly as needed, rather than being stored and released

Question 41

why are steroid hormones made as they are needed?

Answer 41

This is because they are highly lipophilic (lipid soluble) so cannot be retained within lipid membranes

Not stored as they can easily move across the membrane

Question 42

What happens once steroid hormones are synthesized?

Answer 42

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

Question 43

How are steroid hormones transported?

Answer 43

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)

Don’t dissolve very well in water so don’t transport great in plasma

Bind to transport proteins prevents them from enzyme degradation

Question 44

what are steroid hormones produced by?

Answer 44

1. Gonads (testes and ovary) – sex steroids
2. Placenta - hCG, sex steroids
3. Kidney - Vitamin D3
4. Adrenal cortex - corticosteriods

Question 45

All steroid hormones are derived from what?

Answer 45

cholesterol

Question 46

How is it determined which specific steroid hormoned is produced?

Answer 46

Which specific steroid hormone is ultimately produced is determined by different cells having different enzymes synthesising different derivatives of cholesterol

Question 47

what is the mechanism of action of steroid hormones?

Answer 47

Because steroid hormones are lipophilic they cross the plasma membrane easily, both into and out of cells. As such their receptors are located inside cells (cytoplasmic or nuclear receptors) and trigger either activation or repression (inhibition) of gene function within the nucleus = genomic effec

Genes control the synthesis of protein so these hormones either increase­ or decrease protein synthesis

Question 48

Do steroid hormones easily cross the cell membrane?

Answer 48

Because steroid hormones are lipophilic they cross the plasma membrane easily, both into and out of cells

Question 49

What is the speed of the mechanism of action of steroid hormones?

Answer 49

This is a relatively slow process so there is a lag time between hormone release and biological effect (hours to days) but effect persists for around the same time. Some evidences suggests steroids may occasionally bind to cell surface receptors → rapid response

Question 50

When are steroid hormones active and non active?

Answer 50

Inactive when bound to carrier protein and only active when free

only unbound hormones can diffuse into the target cell

Amount of free hormone in the plasma stays pretty constant and stable

Question 51

what is the importance of free hormones?

Answer 51

There is a small amount of unbound free steroid/thyroid hormone in the plasma and this is the physiologically important fraction

Only free hormone can diffuse across capillary walls to target cells

Free hormone : hormone-protein complex ratio much in favour of bound (complexed) hormon

The extent of protein binding can have important effects on the hormone’s actions but in health levels of free (active) hormone remain constant. The Law of Mass Action dictates that as free hormone leaves the plasma (taken up by cells) more hormone is released from the carriers. Typically only minute quantities of hormone are required for physiological functions

Free hormone + complexed hormone = Total plasma [hormone]

Question 52

how do steroid/thyroid hormones bind to carrie rproteins and what effects does this cause?

Answer 52

Question 53

what is the importance of bound and unbound hormones?

Answer 53

bound: unbound ratio must be maintained
- as steroid taken up; more is released from carrier
- allows for a reservoir of hormone ready for action
- prolonged activity

Question 54

can only bound or unbound steroid enter cells?

Answer 54

unbound

Question 55

Summary of peptide and catecholamine hormones?

Answer 55

are water soluble, transported in solution in the plasma

are vulnerable to degradation before they reach their target

have a short half-life in the plasma, (time taken for [plasma] concentration to fall by a half), usually minutes. Prolonged action therefore requires continued secretion

Question 56

Summary of steroid (AND thyroid) hormones?

Answer 56

are lipophilic, once made they diffuse across the cell membrane into the blood

circulate in plasma bound to specific transport plasma proteins (eg thryoxine-binding globulin, or albumin) so have longer half-life, usually hours to days

Alter protein synthesis via modifying gene expression thus effect also persists for hours to days

Question 57

What is hormone secretion determined by?

Most endocrine pathways are responsive to what kind of reflexes?

Answer 57

[Hormone]plasma is determined by the balance between secretion and degradation/excretion

In most endocrine pathways, secretion is responsive to negative feedback reflexes e.g. parathyroid hormone

Question 58

Some endocrine pathways also respond to ________ feedback loops e.g. adrenaline

Answer 58

neural

Question 59

Can the secretion of hormones be subject to multiple control mechanisms?

Answer 59

In addition, the secretion of some hormones can be subject to multiple control mechanisms, insulin being one example. Plasma [glucose], autonomic nerve activity, presence of food in the gut, plus additional hormones such as glucagon all influence [insulin]plasma

Question 60

When normal plasma hormone concentration is disrupted homeostatic responses are initiated to reduce impact on end function e.g.

Prolonged exposure to low [hormone]plasma often leads to what?

Answer 60

leads to up-regulation of receptor number (increases tissue sensitivity to hormone)

Question 61

When normal plasma hormone concentration is disrupted homeostatic responses are initiated to reduce impact on end function e.g.

• prolonged exposure to high [hormone]plasma typically leads to what?

Answer 61

leads to down-regulation of receptor number (decreases tissue sensitivity to hormone)

Question 62

Prolonged exposure to high or low hormone concentration in the plasma may affect not only the ________ own receptors but also ________ for other hormones (permissive or antagonistic effects).

Answer 62

May affect not only the hormone’s** own receptors but also **receptors for other hormones (permissive or antagonistic effects)

Question 63

what are the permissive effects of a hormone?

Answer 63

the presence of one hormone enhances the effect of another eg epinephrine causes only modest lipolysis in adipose tissue, but when thyroid hormones are also present, greatly increased lipolysis occurs.

TH causes increased­ synthesis of receptors for epinephrine on adipocytes. TH itself has no effect on lipolysis but is permissive to epinephrine

Question 64

what is the antagonistic effects of a hormone?

Answer 64

The presence of one hormone reduces the effect of another e.g. Growth hormone impairs the response to insulin by decreasing the number of insulin receptors on tissues

Question 65

Most hormones are released in ____ bursts so [hormone] varies widely. Clinical relevance is that single values of [hormone] may be _________. 24 hour monitoring may be required to give the true picture of hormone levels.

Answer 65

Most hormones are released in short bursts so [hormone] varies widely. Clinical relevance is that single values of [hormone] may be misleading. 24 hour monitoring may be required to give the true picture of hormone levels.