E1 - Review of Hormonal Mechanisms Flashcards
What are the characteristics of a hormone?
- Chemical messengers that normally ‘arouse/excite’
- Secreted directly into the bloodstream from (ductless) endocrine gland
- Target cell/tissue is a long distance from gland
What are the 4 types of intercellular messengers in the body and their characteristics?
- Endocrine (internal/ductless/distance to target/in blood circulation e.g. insulin)
- Autocrine (affects own cell locally e.g. prostaglandins) & Paracrine (within interstitial fluid to neighbouring cell e.g. somatostatin)
- Neuroendocrine - nerve fibres/endo (e.g. hormone made in nerve cell then stored in secretory granules of the axon terminus; e.g. from posterior pituitary gland releasing ADH; arginine vasopressin)
- Neurotransmitter (made by neurones, travels short distance across synaptic cleft e.g. ACh, Glu)
What are the 3 main types of hormones according to chemical structure?
- Peptide hormone
- Steroid hormone
- Hormones derived from tyrosine (starting hormone)
What do peptide hormones consist of? Give examples.
- Chains of amino acids, from 3AAs to 180AAs
- Includes those from hypothalamus, anterior/posterior pituitary gland, pancreas, GIT.
What are steroid hormones derived from? Give examples.
- Cholesterol
- E.g. Adrenal cortex: cortisol, aldosterone
Gonads: sex hormones
Give examples of hormones derived from tyrosine and their characteristic properties.
- Thyroid hormones
- Catecholamines (e.g. adrenaline/noradrenaline/dopamine; has catechol group - lots of NH2)
What are the 5 steps of peptide hormone synthesis?
- ) Gene > mRNA (transcription), mRNA > protein (translation; making a protein from mRNA
- ) PREPROHORMONE made in ribosomes (on RER/in cytoplasm), peptide chain also undergoes protein folding/disulphide bridging and glycosylation attachment of carbohydrates)
- ) Peptide travels through RER stack and ‘pre’ signal peptide bit is cleaved; leaving a PROHORMONE which is packaged into vesicles to the Golgi complex
- ) Peptide undergoes further processing through Golgi complex stack, packaged into secretory granules to form the mature HORMONE
- ) Hormone stored in secretory granules until its required/stimulus; where secretory granule moves towards plasma membrane, fuses then expulsion of hormone into circulation (exocytosis)
What does the ‘pre’ part of the preprohormone entail?
Hydrophobic short sequence; signal peptide (telling cell the protein needs processing/packaging for exporting)
What is the difference in hormone release re. peptide and steroid hormones?
Peptide; release dependent on exocytosis (hormone stored in secretory granules)
Steroid; release dependent on hormone synthesis (biosynthetic enzyme activity) and is via simple diffusion; not stored.
How are steroid hormones released via simple diffusion?
Due to the lipophilicity of steroid hormones; they are attracted to the phospholipid bilayer (plasma membrane) and are led out of the cell that way.
How do steroid hormones travel in the blood?
Once release from an endocrine cell via simple diffusion, they are bound by plasma proteins.
Why do peptide hormones circulate as free hormones/how does it affect half-life?
- Due to solubility; hydrophilic, water soluble nature; likes aqueous environments
- But proteases present in the blood/at target tissue, thus half-life is matter of minutes
What is half-life?
Time taken for initial concentration to fall by 50%
How do steroid/thyroid hormones achieve the longer half-life of hours - days and what advantages does this pose?
- Bound reversibly to plasma proteins (weak bonding; can’t travel as free hormone as lipophilic - not water soluble)
- Protects hormone, delaying metabolism and providing a circulating reservoir
Do peptide hormones act intracellularly at the target cell?
No; they are hydrophilic and thus cannot cross the fatty plasma membrane.
They interact via cell surface receptors in the plasma membrane.
What are the two main types of cell surface receptors for peptide hormones? Give examples of their substrates.
- G-protein e.g. glucagon
- Tyrosine kinase e.g. insulin
What changes occur upon peptide hormone docking?
- Signal transduction of hormone via 2nd messenger
- Physiological changes; altered activity of enzymes or ion channels
- Altered gene expression of specific proteins
Where are intracellular receptors located for steroid hormones?
- Cytosolic
- Nuclear (usually)
What are the consequences of steroid hormone binding?
- An increase or decrease in gene expression (depending on whether stimulating/inhibiting)
What does an increase in gene expression from a stimulating steroid hormone entail?
- Upregulation of gene = increased transcription/translation = more protein present = greater enzyme activity/more ion channels present etc)
Where are hormones metabolised?
Most hormones metabolised by enzymes in liver, kidney and/or blood; little metabolism by target tissues (most of the hormone already metabolised before arriving to target)
How are hormones excreted?
- Via the kidney = urine
- Via the gut = faeces
What are the two feedback regulation processes?
- Negative feedback; consequence (B) negatively controls process (A) to maintain a set point; narrow range maintained.
- Positive feedback; consequence (B) amplifies/enhances process (A) further
What is simple feedback regulation?
- Gland releases hormone, hormone acts at target tissue, target tissue’s response influences OG gland.
What is the endocrine axis?
Interactions between hypothalamus (releasing hormone), anterior pituitary (tropic hormone) and peripheral endocrine glands (peripheral hormone) in series with feedback regulation of hormone secretion
What occurs re. the endocrine axis if the level of peripheral hormone is too high?
- Negative feedback loop to anterior pituitary (direct) and hypothalamus (indirect)
- Thus less release of releasing hormone from hypothalamus
- Thus less release of tropic hormone from the anterior pituitary
- Restoring peripheral hormone level to the set point
What are neuroendocrine reflexes?
Regulatory input from higher centres in the brain above the hypothalamus e.g. STRESS on cortisol release = more produced to deal with stress situation.
What do diurnal and circadian mean?
- Day-night
- Around a day
How does diurnal rhythm influence hormone release in relation to cortisol?
- Body prepares you with high levels of cortisol at the start of the day (to deal w/mini-stresses)
- Body produces more cortisol at late-evening period to deal with rest of the day
- Body produces cortisol during sleep in preparation for the next day
What are the 3 endocrine disorders?
- Hypersecretion (hormone excess) e.g. tumour or immunological factor like Graves’ disease
- Hyposecretion (lack of hormone) e.g. lack of enzyme genetically, immunological attack, destruction by disease, surgical removal
- Decreased target-cell responsiveness; at receptor level or downstream enzyme
What is the difference between a primary disorder and a secondary disorder (relating to endocrine)?
- Primary; dysfunction originating in the peripheral endocrine itself (the OG)
- Secondary; under/overstimulation of the anterior pituitary one above the endocrine axis/excess production of preceding tropic hormone from external source
What investigations/tests are undertaken for suspect endocrine abnormalities?
- ) Signs & symptoms
- ) Endocrine investigations (hormone levels)
- ) Imaging (CT scan etc)
What endocrine investigations/hormone level tests are available?
a. ) Single-point (baseline)
b. ) Dynamic/provocative; checking integrity of feedback control
What testing method is used for suspected hyposecretion and how does it show it?
Stimulation; hormone levels rise in the norm, failure to stimulate indicates hormone insufficiency (often regarded as confirmatory test)
What testing method is used for suspected hypersecretion and how does it show it?
Suppression; hormone levels fall in the norm, failure to suppress indicates autonomous secretion (tumour).
What is the treatment for hormone deficiency?
Synthetic hormone replacement
What is the treatment for excess hormone?
Drugs to block productoin
What is the treatment for decreased target-cell responsiveness?
Drugs to enhance cellular response to hormone
