Receptors and Signalling Flashcards
What is an endocrine gland?
Individual cells or groups of cells which are organised into endocrine glands
They release hormones into the ECF where the hormone will diffuse into the capillary system
What is the function of exocrine glands?
Secrete into a ductal system which then secretes into specific places
How can a hormone be transported throughout the body?
Can be dissolved in the blood or be bound to proteins
What is determines the specificity of signaling?
Chemically distinct hormones
Specific receptors for each hormone
Distance distribution of receptors across target cells
What are the major endocrine glands?
Pituitary Thyroid Parathyroid Adrenal Pancreas Ovary Testis
What are the 4 classes of horomes?
Modified amino acids
Steroids
Peptides
Proteins
What are some examples of modified amino acid hormones?
Adrenaline Thyroid hormones (T3 and T4)
What are some examples of steroid hormones?
Cortisol
Progesterone
Testosterone
What are some examples of peptide hormones?
ACTH
ADH
Oxytocin
What are some examples of protein hormones?
Insulin
What does the chemistry of the hormone determine?
Half life of hormone
Whether the hormone will stay in the ECF or ICF
Volume of distribution
What is autocrine signalling?
The cell signals to itself
What is paracrine signalling?
Cell signals to its close neighbours
What is endocrine signalling?
The signalling molecule enters the bloodstream
How is the action of an endocrine hormone terminated?
Enzyme-mediated metabolic inactivation in the liver or sites of action
What hormones contribute to the response of the body to short-term intense exercise?
Adrenaline
Cortisol
Glucagon
What hormones contribute to normal growth?
GH
Insulin
IGF-1
Sex steroids
What is the basic action of insulin?
Lowers plasma glucose by inhibiting hepatic glycogenolysis and gluconeogenesis and stimulating glucose uptake into muscle and adipose tissue
What is the basic action of glucagon?
Increased plasma glucose levels by stimulating hepatic glycogenolysis and gluconeogenesis
What hormone antagonizes glucose uptake into muscle and adipose tissue?
Adrenaline
What is the synthesis, storage and release of amines?
Pre-synthesised and stored in vesicles
Released in response to calcium induced exocytosis
Hydrophilic so are transported freely around the bloodstream
What is the synthesis, storage and release of peptides and proteins?
Pre-synthesised from a longer precursor
Stored in vesicles
Released in response to stimuli by Ca2+ dependent exocytosis
Hydrophilic so are transported freely around the blood
What is the synthesis, storage and release of steroids?
Synthesised and secreted upon demand
Stimuli will increase cellular uptake and availability of cholesterol and the rate of conversion of cholesterol to pregnenolone
There is no storage in vesicles, it is released as soon as its made
They are hydrophobic so are transported bound to plasma proteins
What is the function of carrier proteins?
Increase the amount of hormone carried in the blood
Provide a reservoir of hormone
Extend the half life of the hormone in circulation
What will bind to cortisol-binding globulin?
Cortisol
What binds to thyroxin-binding globuin?
Thyroxine (T4) and also some T3
What binds to sex steroid binding globulin?
Testosterone and oestradiol
What binds to albumin?
Steroids and thyroxine
What binds to transthyretin?
Thyroxine and some steroids
When will steroid hormones be biologically active?
Only once they have dissolved in the plasma and dissociated from the carrier protein
How is the concentration of steroid hormones in the plasma kept relatively constant?
Free hormone removed from the plasma by elimination is replaced by bound hormone dissociating from the carrier protein - the carrier protein acts as a reservoir
Describe the HPA axis?
Hypothalamus secretes CRF which stimulates the anterior pituitary to release ACTH which acts on the adrenal cortex to release cortisol
How does the HPA axis act as a negative feedback loop?
Cortisol acts on the anterior pituitary and hypothalamus to reduce the ability to release CRF and ACTH
What is the equation for plasma conc of hormones?
Plasma conc = rate of secretion - rate of elimination
What are the different chemical classes half life?
Amines: seconds
Proteins and peptides: minutes
Steriods: hours to days
What hormones activate GPCR receptors?
Amines and some proteins/ peptides
What hormones activate receptor kinases?
Insulin - protein
What hormones activate nuclear receptors?
Steroid hormones and thyroid hormones
What are the different classes of nuclear receptors?
Class 1: located in cytoplasm bound to inhibitory heat shock protein and dissociate from this when ligand binds and moves to nucleus
Class 2: activated by lipids - present in nucleus
What is the signalling pathways of GCRP receptors Gi and Gs?
Gs, Gi proteins via adenyly cyclase, cAMP and PKA
What effect does Gs have on adenyly cyclase?
Increased rate of production of cAMP from ATP
What effect does Gi have on adenyly cyclase?
Reduces the rate of production of cAMP from ATP
What does cAMP do?
Phosphorylates PKA which causes the phosphorylation of Ser/Thr residues in target proteins causing the cellular effects
What is the signalling pathways of GCRP receptor Gq?
Via PLC, PKC, IP3 calcium and DAG
What hormones act through the Gq signalling?
Angiotensin 2
Gonadotropin releasing hormone
Thyrotropin releasing hormone
What hormones act through the Gs signalling?
Adrenaline
Corticotrophin releasing factor (CRF)
Glucagon
What hormone acts through the Gi signalling?
Melatonin
What happens when insulin binds to its receptor kinase?
Autophosphorylation of intracellular tyrosine residues that causes the recruitment of multiple adapted proteins such as insulin receptor substrate protein that is phosphorylates by tyrosine
What does the insulin receptor substrate protein do?
Activates protein kinase B which causes the desired metabolic effects
What hormones does the anterior pituitary produce?
These are all peptide or protein
ACTH (acts on adrenal cortex) GH (acts on liver, bones and muscle) FSH (acts on gonads) Luteinizing hormone (acts on gonads) Prolactin (acts on mammary glands) TSH (acts on thyroid)
What hormones does the posterior pituitary produce?
These are all protein or peptide
ADH (acts on renal cortex)
Oxytocin (acts on mammary glands and uterus)
What hormones does the thyroid produce?
These are all modified amino acids
Thyroxine (acts on most tissues)
T3 (acts on most tissues)
What hormones does the parathyroid produce?
These are all peptide or protein
Calcitonin (acts on bone and gut)
PTH (acts on bone and gut)
What hormones does the adrenal cortex produce?
These are steroid
Zona glomerulosa - aldosterone
Zona fasciculata - cortisol
Zona reticularis - androgens
SALT, SUGAR, SEX
What hormones does the adrenal medulla produce?
These are modified amino acids
Adrenaline and noradrenaline
What hormoens do the female and male gonads produce?
These are steroids
Male: testosterone
Female: Oestroadiol and progesterone
What hormones do the placenta produce?
These are peptides and steriods
hCG
Oestradiol
Progesterone
