A. HORMONAL MECHANISMS Flashcards
what does endocrine mean
internal/inside
what does exocrine mean
external/outside
what is a endocrine hormone
a chemical messenger secreted directly into the bloodstream from (ductless) endocrine gland which targets cell/tissue some distance from endocrine gland
DON’T LEAVE THE BODY
what is a exocrine hormone
a chemical messenger released through a duct or opening to body surface from exocrine gland (eg - sweat or salivary gland)
example of endocrine intercellular messenger in body
insulin which is released from islets of Langerhans (pancreas), enters bloodstream and acts on liver, adipose tissue, skeletal muscle which are are the 3 main metabolic organs in the body
what are autocrine hormones
released by cell into interstitial fluid and then acts on same cell
example of autocrine intercellular messenger in body
prostaglandins
what are paracrine hormones
released by cell, travels a short distance in interstitial fluid and then targets neighbouring cells
example of paracrine intercellular messenger in body
somatostatin on insulin secretion
what are neuroendocrine hormones/neurohormones
released from nerve cell/neuroendocrine cell along axon into bloodstream and then act on target cell
example of neuroendocrine intercellular messenger in body
oxytocin and arginine vasopressin (antidiuretic hormone) secreted from posterior pituitary gland
what are neurotransmitters
released from neurone, cross synaptic cleft and act on another neurone
example of neurotransmitter intercellular messenger in body
acetylcholine
what are peptide hormones
chains of amino acids and includes those released from hypothalamus, anterior and posterior pituitary, pancreas and GIT
what are steroid hormones
derived from cholesterol (in membrane) and includes cortisol, aldosterone (adrenal cortex) and sex hormones (gonads)
what are hormones derived from tyrosine
thyroid hormones and catecholamines (adrenal medulla)
eg - Adr, NA, dopamine
what are eicosanoids
prostaglandins
peptide hormone synthesis
NUCLEUS
- gene to mRNA by transcription
- mRNA to protein by translation
RER AND RIBOSOMES
- preprohormone which undergoes protein folding, disulphide bonding, glycosylation and ‘pre’ signal is cleaved
GOLGI COMPLEX
- prohormone which undergoes additional processing and cleavage
SECRETORY GRANULES
- hormone is packaged into granules, stored until released upon arrival of stimulus and then released by exocytosis
what is exocytosis
fusion with plasma membrane and hormone release
how do you increase the rate of peptide hormone release
increase the rate of exocytosis
steroid hormone synthesis
(no gene involved)
- there is a precursor molecule (cholesterol-based) and biosynthetic enzymes in SER and mitochondria
- the hormone is not stored
- the hormone is lipophilic so can pass easily through membrane
- not soluble in blood (aq) so makes weak, reversible bonds with plasma proteins
- hormone is released by simple diffusion
how do you increase the rate of steroid hormone release
increase steroid hormone production
what are peptide hormones half life
- minutes due to proteases in plasma
- the unbound/free hormone is biologically active
what are steroid hormones half life
- hours to days
- protected by plasma proteins
- metabolism is delayed and therefore there is a circulating reservoir of hormones and it can’t interact with target
peptide hormone action
Act on plasma membrane receptors as they are hydrophilic
- GPCR
eg: glucagon via GS, adenylyl cyclase/cAMP
- hormone binds to GPCR, effector then signal transduction occurs - tyrosine kinase receptor
eg: insulin
- hormone binds to receptor and signal transduction occurs
signal transduction causes a physiological response where there is altered activity of enzymes or ion channels or altered expression of specific proteins
steroid hormone action (and thyroid hormones)
Act on intracellular receptor as they are lipophilic
- cytosolic receptor
- hormone binds to receptor and then the complex binds to promoter region of DNA
- DNA to mRNA, increased or decreased gene expression causing changes to proteins and biological effects - nuclear receptor
- hormone diffuses into nucleus
intracellular receptors act as hormone-regulated transcription factors
how long does steroid hormone action take
hours/days as changing gene transcription but if there are plasma membrane receptors which will cause a faster effect
where are hormones metabolised
- by enzymes in liver, kidney or blood
- small proportion by target tissues
- excreted in urine or faeces
how does feedback regulation regulate hormone release
consequence of a process acts to regulate the rate at which the process occurs
what is negative feedback
consequence negatively controls process to maintain a set-point
(the basis of homeostasis)
what is positive feedback
consequence enhances or amplifies process further
(not homeostasis)
ie - chemical reaction which causes heat to be released, explosion?
example of simple regulation to regulate hormone release
beta-cell gland releases insulin from islets of Langerhans which targets liver/skeletal muscle/adipose tissue and causes a decrease in glucose concentration
example of feedback regulation in which the hypothalamic and pituitary tropic hormones are involves (endocrine axis)
if there is too high a level of peripheral hormones, negative feedback on anterior pituitary gland which decreases amount of tropic hormone released
what is the endocrine axis
interactions between the hypothalamus, pituitary and peripheral endocrine glands showing feedback regulation to maintain physiological homeostasis
how does neuroendocrine reflexes cause regulation of hormone release
input from higher centres in brain
example of a neuroendocrine reflex
increased production of cortisol due to feedback regulation of cortisol (stress hormone) production
how does diurnal (day-night) or circadian (around a day) rhythm cause regulation of hormone release
- cortisol levels are normally high in the morning and trough in the late evening
- with diseases there is a different pattern
- use when sampling for clinical or experimental reasons
what causes endocrine disease caused by hypersecretion
tumour or immunological factor (Graves’ disease)
what causes endocrine disease caused by hyposecretion
genetic deficiency of enzyme making hormone, immunological attack, destruction by disease, surgical removal
what causes endocrine disease caused by decreased target-cell responsiveness
at level of receptor or downstream enzyme
what is primary endocrine disease
associated with gland making the hormone
what is secondary endocrine disease
due to another condition or abnormal hypothalamic-pituitary secretion of tropic hormone
example of hypersecretion endocrine disease
Cushing’s syndrome (excess cortisol)
primary defect - tumour in adrenal cortex making too much
secondary defect - tumour in anterior pituitary producing too much ACTH
or due to a different condition with an ectopic ACTH-producing tumour
how to investigate endocrine disorders
- signs and symptoms
- endocrine investigations (hormone levels)
- imaging: tumour?
endocrine investigations
1) single point (base-line blood tests)
2) dynamic provocative tests to check integrity of feedback control
stimulation tests (used for hypo secretion)
- failure to stimulate indicates hormone insufficiency (confirmatory test)
suppression tests (used for hyper secretion)
- failure to suppress indicates autonomous secretion (tumour)
how to treat hormone deficiency
hormone replacement
how to treat hormone excess
drugs to block production or to block hormone receptor (antagonist)
how to treat decreased target-cell responsiveness
drugs to enhance cellular response to hormone
how to treat a tumour
radiotherapy or surgery