Endocrine Flashcards
What are the four different types of hormones based on their mechanism of signalling
Endocrine hormones - chemical messengers that travel through circulation to reach distant target cells
Paracrine hormones - travel a relatively short distance
Autocrine hormones - act on the cells that synthesise and secrete them
Juxtacrine hormones - act on the cells in direct contact with them
How are hormones classified based on composition
Peptide hormones
Amino acid derivatives
Lipid derivatives
What are peptide hormones
Relative short, defined amino acid chains e.g. insulin, glucagon
Bind receptors at the plasma membrane
Exert their biological effects through plasma membrane receptors
What are amino acid derivatives
Derived from tyrosine e.g. epinephrine, norepinephrine (catecholamines) and thyroxine and triiodothyronine (thyroid hormones)
What are lipid derivative hormones
Steroid hormones derived from cholesterol e.g. testosterone, oestradiol, progesterone, cortisol, aldosterone
Exert their biological effects through intracellular receptors
How are hormones classed based on mechanism of action
- Receptors for protein based hormones exist on plasma membranes
- Receptors for lipid based hormones exist inside the cell
What are the 8 typical steps in signal transduction
- Synthesis of the signalling molecule
- Release from the signalling cell
- Transport to the target cell
- Binding to and activation of the target receptor
- Transmission of one or more intracellular signals from the
activated receptor - Arrival of the message at the final destination of the cell
- Changes in cellular function in response to the signal
- Termination of the signal and subsequent termination of the
cellular response - Binding of hormone to its receptors is non-
covalent & reversible
What are plasma membrane receptors composed of
– An extracellular domain (binds hormone)
– A membrane spanning region (hydrophobic)
– An intracellular domain (interacts with intracellular molecules)
Hormone binding causes conformational change of the receptor
Give an example of a plasma membrane receptor and explain how it works
– Interacts with and activates a G protein
– G proteins interact with and activate plasma membrane enzymes
– Activated enzymes catalyse biochemical reactions which result in
an increase in a second messenger
– The second messenger brings about a cellular response to the
hormones signal
Explain how lipid hormones exert their biological effects
Inactive receptors are bound in large protein complexes in the
cytosol
* Protein complexes contain inhibitor proteins such as Heat
Shock Proteins (e.g.HSP90)
– Confine the inactive receptors to the cytosol
* On binding of the ligand to its homodimeric receptor, inhibitor
proteins dissociate
* The active receptor translocates to the nucleus
* Ligand-receptor complexes bind DNA directly at hormone
response elements (HREs)
– Regulates gene transcription
What is the role of hormones in physiological homeostasis
Hormones alter the operation of target cells by changing the types, quantities or activities of important proteins
– Stimulate the synthesis of proteins not already present in the cell by activation of gene transcription
– Increase/decrease the rate of gene transcription and protein translation
– Turn on/off an existing protein by modification of its shape or structure (e.g. activation/inactivation of proteins through phosphorylation)
What is the role of the hypothalamus
Regulates the neuroendocrine system
Central nervous system receives information from internal and external sensors about danger, hunger, diet, blood composition
Hypothalamus regulates the production of appropriate hormones by endocrine
glands
What are the six components of organisation of the endocrine system
Stimulus
Neuronal response
Releasing factors -> hypothalamus
Stimulating factors -> pituitary gland
Effector hormones -> endocrine gland
Response -> target cell
Write about feedback control of endocrine secretion
- Hypothalamus secretes a releasing hormone which stimulates
hormone production from the pituitary gland - Endocrine hormones produced act on target cells to maintain
physiological homeostasis - Once homeostasis is restored hormone production must be
reduced
Positive or negative feedback
What is negative feedback
Most common mechanism of hormonal regulation
Hormone 1 stimulates production of hormone 2 which feeds back to inhibit cell production of hormone 1
What is positive feedback
Hormone 1 stimulates production of hormone 2 which stimulates production of hormone 1
Give an example of negative feedback
LH from pituitary
stimulates testis to produce
testosterone which feeds
back to inhibit LH secretion
from the pituitary
Give an example of positive feedback
LH stimulates ovaries
to secrete oestrogen which
stimulates LH secretion
from the pituitary (surge of
LH at ovulation)
Write about signal amplification
- At each level in the signalling cascade,
a small signal elicits a much larger
response - Hormones are very potent only
present in trace amounts - Endocrine systems allow amplification
of the initial signal
What is an endocrine disorder
A process which changes the amount or activity of a hormone results in an endocrine disorder
- Overproduction
- Underproduction
- Resistance to the hormone action
What is an endocrine disorder
A process which changes the amount or activity of a hormone results in an endocrine disorder
- Overproduction
- Underproduction
- Resistance to the hormone action
List seven endocrine disorders
Diabetes Mellitus
Acromegaly
Addison’s disease
Cushing’s Syndrome
Hyperthyroidism
Hypothyroidism
Prolactinoma
Write about acromegaly
Increase in growth hormone
Write about addison’s disease
Decreased hormones of the adrenal glands
Write about cushings syndrome
Cortisol levels up
Write about hyperthyroidism
Thyroid up
Grave’s disease -> thyroid hormone up
Write about hypothyroidism
Thyroid down
Hashimoto’s thyroiditis -> thyroid hormone down
Write about prolactinoma
Prolactin by the pituituary gland up
Write about overproduction endocrine disorders
Hormone excess can occur when an endocrine gland overproduces it e.g. tumours in an endocrine tissue may lead to unregulated hormone production
Ectopic production of the hormone e.g. a tumour in a non-endocrine tissue acquires the ability to secrete the hormone
Write about underproduction endocrine disorders
Hormonal deficiencies develop when the endocrine cells are
damaged/destroyed:
– Direct infection
– Ischemia (i.e. oxygen starvation)
– Compression (e.g. by a tumour)
– Autoimmune condition
Can also be due to:
– Decreased stimulation of hormone production by
upstream hormones
– Genetic defects in production of the mature hormone e.g.
enzymes missing from the biosynthetic pathway
Write about hormone resistance endocrine disorders
A state where the hormone is present at normal or
increased levels, but the expected physiological response
does not exist
– e.g. insulin resistance in type 2 diabetes mellitus
* Can be due to a receptor defect or downstream
signalling defect
– i.e. genetic defect in a hormone recepto
classify endocrine disorders
Primary 1’ disease
Seconday
Tertiary
What is a primary disease
Defect in the end/target endocrine gland
What is a secondary disease
Defect in the pituitary gland (stimulating factor)
What is a tertiary disease
Defect in the hypothalamus (releasing factor)
What is a tertiary disease
Defect in the hypothalamus (releasing factor)
Write about primary hypothyroidism
1’ defect directly involves the endocrine gland:
– e.g. 1 hypothyroidism due to underactive thyroid gland and
reduction in thyroxine (T4) production
Write about secondary hypothyroidism
2’ defect involves the pituitary gland:
– e.g. 2’ hypothyroidism due to decreased production of thyroid
stimulating hormone (TSH) from the pituitary gland
Write about tertiary hypothyroidism
3’ defect involves the hypothalamus:
– e.g. 3’ hypothyroidism due to decreased production of
thryotropin releasing hormone (TRH) from the hypothalamus
Describe the synthesis of thyroid hormones
Tyrosine + iodine forms T3 and T4
Write about thyroid hormones
The thyroid gland produces thyroxine (T4) and tri-
iodothryonine (T3) in response to TSH
– ‘Stored’ in thyroglobulin & bound to protein in the blood
* Gland mainly produces T4
– Converted to T3 in liver and kidney
* T3 is the more potent thyroid hormone
* Thyroid hormones regulate metabolism, growth and development in virtually all cells through their regulation of gene expression
* Usually only a very small fraction of a circulating hormone is free (unbound) and biologically active
* 99% of T3 and T4 are bound to transport proteins in the blood:
– Thyroid binding globulin ~ 70%
– Transthyretin ~ 20%
– Albumin ~ 10%
* Carrier protein association increases the hormones stability and half life in circulation
* Only the free hormone is active
What are four symptoms of hypothyroidism
Sluggish metabolism
Weight gain
Tiredness
Depression
What causes hypothyroidism
Inflammation
Surgery/anti-thyroid drugs
Congenital hypothyroidism
Iodine deficiency
What are four symptoms of hyperthyroidism
Increased heart rate
Increased metabolic rate
Weight loss
Sweating
What causes hyperthyroidism
Grave’s disease
Adenoma
Inflammation
Iodine excess
Write about thyroid function tests
- First line tests for the laboratory assessment of thyroid function
are TSH, free-T4 (and free-T3)
– Thyroid stimulating hormone approximately 0.4-4.5 mIU/L
– Free-thyroxine (FT4) approximately 10-30 pmol/L
– Free- tri-iodothryonine (FT3) approximately 3-9 pmol/L - The pattern of results obtained from these tests can point
towards the cause of the disorder
What is the best single test to assess thyroid function
Thyroid stimulating hormone
If it is normal a disorder can generally be excluded
What does Los TSH plus low FT4 indicate
2’ hypothyroidism
What does low TSH plus high FT4 indicate
1’ hyperthyroidism
What does high TSH plus low FT4 indicate
1’ hypothyroidism
What does high TSH plus high FT4 suggest
2’ hyperthyroidism
