Diabetes and Endocrinology Welcome Introduction & Case Launch

Question 1

Define the term ‘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.

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 2

Define the term ‘hormone’.

Answer 2

a

Question 3

Define the term ‘neurohormone’.

Answer 3

a

Question 4

Define the term ‘endocrinology’.

Answer 4

a

Question 5

Describe the ‘life history’ of a typical hormone.

Answer 5

a

Question 6

Classify hormones according to their chemistry and mechanisms of action upon target cells.

Answer 6

Peptide or protein hormones – composed of chains of amino acids (most common).

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

Steroid hormones – all derived from cholesterol.

Question 7

State in logical sequence the factors that determine the availability of a hormone or neurohormone to its target cells.

Answer 7

a

Question 8

List major categories of physiological function that are governed by endocrine pathways and mechanisms.

Answer 8

a

Question 9

Describe the main routes and types of signal that determine the rates of hormone synthesis and secretion by a typical endocrine cell.

Answer 9

a

Question 10

Endocrine hormones should not be confused with;

Answer 10

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

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

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

Question 11

Describe endocrine communication.

Answer 11

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 12

Describe neural communication.

Answer 12

Neurotransmitters released from presynaptic neurons travel across the synaptic cleft to the postsynaptic cell to influence its activity.

Question 13

Describe how endocrine and neural communication contrast one another.

Answer 13

Neurotransmitter is the chemical released by the neuron and acts locally within the synaptic cleft.
In contrast, hormones released by endocrine cells act distally.

Question 14

Why do the endocrine and neural communication cooperate?

Answer 14

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

Question 15

Describe neuroendocrine communication.

Answer 15

The endocrine and nervous systems combine. Nerves release hormones, which enter blood and travel to their target cells e.g. hypothalamic – posterior pituitary axis.

Question 16

How is the response to a hormone highly specific?

Answer 16

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 17

What is the function of hormones (and neurotransmitters)?

Answer 17

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).

Question 18

In what systems is endocrine function involved?

Answer 18

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 19

Is the endocrine system anatomically continuous?

Answer 19

No - the various glands form individual functional systems.

Question 20

Describe the features of an endocrine hormone.

Answer 20

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

Question 21

Describe the synthesis of a peptide hormone (and give examples).

Answer 21

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).

e.g. TRH, FSH, insulin.

Question 22

Describe the clinical use of C-peptide in diabetes.

Answer 22

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.

Question 23

Describe the mechanism of action of peptide hormones.

Answer 23

Water soluble so dissolve easily in plasma making transport via the blood simple and easy. However, water solubility means they cannot cross cell membrane so they must bind to membrane bound receptors on the target cell.

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 24

State the two receptors through which peptide hormone is transducted.

Answer 24

G protein-coupled receptor - activates 2nd messenger system and/or ion channels leading to modification of existing proteins. Rapid response.
OR
Tyrosine kinase linked receptor: alters gene expression*. Slower, longer lasting activity.

*2nd messengers may also alter gene expression.

Question 25

Describe the synthesis of amine hormones (and give examples).

Answer 25

Most are derived from the amino acid, tyrosine. The only exception is melatonin, which is derived from tryptophan.

Catecholamines have a similar mechanism of action to peptide hormones (hydrophilic).
e.g. dopamine (CNS NT), norepinephrine (NT), epinephrine (hormone released by adrenal medulla).

Thyroid hormones have a similar mechanism of action as steroid hormones (lipophilic).
e.g. thyroxine, triiodothyronine.

Question 26

Describe the synthesis of steroid hormones.

Answer 26

Unlike the other types of hormones, steroid hormones are synthesised directly as needed, rather than being stored and released. This is because they are highly lipophilic so cannot be retained within lipid membranes. Once synthesised 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 27

State organs that produce steroid hormones and give examples of the hormones they produce.

Answer 27

Gonads (testes and ovary) – sex steroids

Placenta - hCG, sex steroids

Kidney - Vitamin D3

Adrenal cortex - corticosteriods

Question 28

How are specific steroids produced?

Answer 28

All steroid hormones are derived from cholesterol. Which specific steroid hormone is ultimately produced is determined by different cells having different enzymes synthesising different derivatives of cholesterol.

(This common ancestry also explains why there are cross effects of excess steroids).

Question 29

Describe the mechanism of action of steroid hormones.

Answer 29

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

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

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 evidence suggests steroids may occasionally bind to cell surface receptors causing a rapid response.

Question 30

Define the term ‘free hormone’.

Answer 30

A hormone-protein complex ratio much in favour of bound (complexed) hormone.

Question 31

Describe the Law of Mass Action.

Answer 31

As free hormone leaves the plasma (taken up by cells), more hormone is released from carriers. Typically only minute quantities of hormone are required for physiological functions.

• Allows for a reservoir of hormone ready for action
• Prolonged activity

Question 32

Describe the unique physiological activity of free hormones.

Answer 32

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.

Question 33

Explain how to calculate total plasma [hormone].

Answer 33

Free hormone + complexed hormone.

Question 34

What determines [hormone] in plasma?

Answer 34

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

Question 35

What determines hormone secretion? Give examples.

Answer 35

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

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

Question 36

Name multiple control mechanisms, which act on insulin.

Answer 36

Plasma [glucose], autonomic nerve activity, presence of food in the gut, plus additional hormones such as glucagon all influence [insulin] in plasma.