Introduction Flashcards
Define the endocrine system
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
Define hormone
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.
Define neurohormone
A neurohormone is a hormone such as vasopressin or noradrenaline produced by nerve cells and secreted into the circulation.
List the 6 features of an endocrine hormone
- 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
How do we classify endocrine hormones?
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)
How are peptide hormones stored?
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
What inactive peptide is linked to insulin as its prohormone form, and what is its clinical significance?
C-peptide
Reflects endogenous insulin production, though levels are roughly 5x higher than blood insulin as insulin is metabolised faster
Describe the mechanisms of action of peptide hormones
Water soluble so transported via blood to specific cell surface receptors
Linked to either GPCRs (fast responses) or TK receptors (slow responses)
Give some examples of peptide hormones
Insulin
Thyrotropin-releasing hormone (TRH)
Follicle stimulating hormone (FSH)
Why are GPCR responses fast and TK responses slow?
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.
What type of receptor is the insulin receptor?
Tyrosine kinase receptor
Describe steroid hormones
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)
Describe the transport of steroid hormones to their target sites
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)
What is the half life of steroid hormones?
60-90 mins
What is the half life of amine hormones?
2 mins
Where are some steroid hormones produced, giving examples of what these glands produce?
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
What are all steroid hormones derived from?
Cholesterol
Describe the mechanism of action of steroid hormones
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
Describe the formation of amine hormones
Most amine hormones are derived from tyrosine
All but one, melatonin, which is derived from tryptophan
What are the two classes of amine hormone, and how do they differ in their mechanisms of action?
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)
Describe the law of mass action in terms of hydrophobic amine hormones
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.
Why must the bound:unbound ratio of amine hormones be maintained?
As hormone is taken up, more is released from carrier. This allows for a reservoir of hormone ready for action for prolonged activity
Which hormones have short half lives in plasma (around minutes) and why?
Peptide hormones
Catecholamines from amine hormones
Hydrophilic, prone to degradation before reaching target, require continued secretion for prolonged action. Also are excreted rapidly
What hormones have long half lives in plasma and why?
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.
How are hormones removed?
Excretion by kidneys into urine
Metabolised by the liver
How is hormone secretion regulated?
Negative feedback loops (by physiological response or product, short loop vs long loop)
Neural feedback loop
What is growth hormones affect on insulin receptor expression?
GH causes down regulation of insulin receptors (those with acromegaly can present with suspected diabetes)
What is a permissive effect?
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.
How many people in Scotland have diabetes?
1 in 20
What % of inpatients have diabetes?
15-20%
What % of total inpatient expenditure is spent on patients with diabetes?
12%
