WEEK 1 Flashcards
What are the three main types of cell communication?
Autocrine, Paracrine and Endocrine signalling
What is autocrine signalling?
Secretory cell=target cell (intracrine=same but acts within same cell rather than binding to cell’s target sites)
What is paracrine signalling?
Secretory cell adjacent to target cell
What is endocrine signalling?
Substance secreted into general circulation and reaches target cell at a distance
What are the nicotinic effects of ACh?
muscle contraction, synaptic transmission (autonomic ganglia, parasympathetic postganglionic, CNS)
What are the receptors that cause nicotinic effects of ACh?
nAChRs (ion channels)
What are the muscarinic effects of ACh?
bradycardia, salivation, bronchospasm, mydriasis
What are the receptors that cause muscarinic effects of ACh?
M1-5 (GPCRs)
How do you measure ligand binding to a receptor?
Radioactive binding assay
Describe the process of radioactive binding assay
add radioactive ligand to sample containing receptor, wash, measure radioactivity
What is the equation for fraction of occupancy?
[Radioactive ligand]/[Receptor(total)]=[L]/[L]+Kd
What is the equilibrium dissociation constant (Kd) and what does it measure?
concentration of ligand where 50% of receptors are occupied by ligand=ligand affinity
What are the four main receptor types?
Ligand-gated ion channels (ionotropic)-eg. nAChRs
G-protein coupled receptors (metabotropic)-eg. mAChRs
Kinase-linked receptors-eg. cytosine receptors
Nuclear receptors-eg. oestrogen receptor
Process of GPCRs
Receptor in plasma membrane is bound by agonist, causes change in receptor conformation, activation, heterotrimeric G protein consistent of alpha, beta and gamma protein reassembles, active G protein receptors interact with G protein bound to plasma membrane by lipid anchors, G protein coupling, alpha, beta and gamma subunits dissociate causing nucleotide exchange-GDP moves off, GTP replaces it, activated G protein subunits regulate effector proteins, beta-gamma dimer formed which activates Ca2+ ion channels, GTP hydrolysis causes inactivation of Galpha protein
What effect does the Gs alpha subunit cause?
ATP-(adenylyl cyclase)->cAMP-(cAMP phosphodiesterase (PDE))->AMP
What effect does the Gq alpha subunit cause?
Gq->Phospholipase C->diacylglycerol-activates Protein Kinase C by binding of InsP3 to channels on ER surface, causing Ca2+ to move out and cause biological response
Describe the process of hormonal regulation of glycogen metabolism
Gs->AC->cAMP->Protein Kinase A
Protein Kinase A causes: Glycogen synthase phosphorylation (inactivation), Phosphorylase kinase phosphorylation (activation) which causes glycogen phosphorylase b to form glycogen phosphorylase a which causes glycogen hydrolysis in the liver
What is the role of Protein kinase?
Protein phosphorylation
What is the role of Protein phosphatase?
Protein dephosphorylation
TSH receptor signalling in the Thyroid with relation to the cAMP/PKA pathway
TSH binds to TSHR, causes Gs alpha subunit to activate adenylyl cyclase which forms cAMP from ATP, which activates Protein Kinase A (PKA), causing transcription of genes that form Tg-1, from which T3 and T4 are formed
What is an autonomous thyroid adenoma (ATA)?
benign tumour in the thyroid gland which causes hyperthyroidism-60% of cases due to activating TSHR mutation
What do homozygous muts suffer from and why?
Severe congenital hypothyroidism due to inactivating TSHR mutations
What do heterozygous muts suffer from and why?
Mild/compensated hypothyroidism due to inactivating TSHR mutations
What is the effect of positive feedback loops?
Stimulatory
What is the effect of negative feedback loops?
Inhibitory
What is a hormone?
A substance secreted directly into the blood by specialised cells which is present in minute concentrations and binds to specific receptors on target cells
What is homeostasis?
The maintenance of a constant internal environment
Describe the endocrine feedback loop
Stimulus activates Gland A which produces Hormone A, which activates Gland B/target tissue which activates Hormone B which causes action. Hormone B also causes inhibition of Gland A and Hormone A.
What are the two types of hormones?
Lipophilic (steroid hormones) and Water-soluble (peptide hormones)
What is a lipophilic (steroid) hormone?
A substance able to pass through the phospholipid bilayer and bind to receptors in the target cell
What is a water-soluble/hydrophilic (peptide) hormone?
A substance unable to pass through the membrane so binds to a receptor on the cell surface and causes conformational change which mediates effects into the cytoplasmic side via secondary messengers
How are hormones regulated?
Biosynthesis Secretion Circulation/distribution Peripheral modification Receptor interaction Hormone metabolism/excretion
What are the basic actions of the thyroid hormones?
basal metabolic rate, growth
What is the basic action of the parathyroid hormone?
Ca2+ regulation
What are the basic actions of cortisol?
glucose regulation, inflammation
What are the basic actions of aldosterone?
BP, Na+ regulation
What are the basic actions of catecholamines?
BP, stress
What are the basic actions of oestradiol?
Menstruation, femininity
What are the basic actions of testosterone?
Sexual function, masculinity
What are the basic actions of insulin?
Glucose regulation
What is the basic action of ANP?
Na+ regulation
What is the basic action of Vitamin D?
Ca2+ regulation
What is the basic action of ACTH?
Adrenal cortex regulation
What is the basic action of TSH?
Thyroid hormone regulation
What are the basic actions of GH?
Growth, metabolism regulation
What are the basic actions of LH/FSH?
Reproductive control
What is the basic action of Prolactin?
Breast milk production
What is the basic action of ADH?
Water regulation
What is the basic action of Oxytocin?
Breast milk expression (lactation)
What is the result of binding of an auto-antibody to TSH receptors?
stimulation of unregulated hyper-production of thyroid hormones with no negative feedback to pituitary gland to secrete less TSH
What is the general management strategy for hormone excess?
Remove/block
What is the general management strategy for hormone deficiency?
Replace
What are three types of glands?
Endocrine, exocrine and mixed glands
What are endocrine glands?
Ductless glands that release secretions (hormones) into the blood directly from cells
What are exocrine glands?
Glands that release their secretions outside the body and may be ducted
What are mixed glands?
Glands that can act as endocrine and exocrine glands
What are the four characteristic differences between the two major regulatory systems of the body (endocrine and nervous systems)?
Many hormones vs. few neurotransmitters
Generally slow vs. generally rapid
Generally long-lasting vs. generally short-lived
Widespread-in blood vs. localised-cell to cell
What are the different mechanisms of chemical signalling?
Neuroendocrine, endocrine, paracrine, autocrine and intracrine.
What is feedback?
Process by which body senses change and responds to it
What is negative feedback?
Process by which body senses change and activates mechanism to reduce it (inhibits hormone release in endocrine cascade)
What is positive feedback?
Process by which body senses change and activates mechanism to amplify it (stimulates hormone release in endocrine cascade)
Process of peptide hormone synthesis, packaging and release
1 ) mRNA on ribosomes binds AA into peptide chain called preprohormone, chain is directed into the ER lumen by a signal sequence of AA
2) enzymes in the ER chop off signal sequence creating inactive prohormone which passes from the ER through the Golgi complex
3) secretory vesicles containing enzymes and prohormone bud off the golgi and enzymes chop the prohormone into one or more active peptides plus additional peptide fragments
4) secretory vesicles release the contents by exocytosis into the extracellular space
5) hormone moves into circulation for transport to target
Where are steroid hormones synthesised?
Adrenal gland
Describe the storage and transport of steroid hormones
Not stored but synthesised in cytosol as required, then diffuse out of the cell and transported as lipoprotein
Process of steroid hormone synthesis
1) hydrolysis of esters and release of cholesterol from the cell membrane
2) cholesterol to pregnenolone in mitochondria
3) processing of pregnenolone to necessary hormone via cell-specific enzymes in SER
4) egress by diffusion/facilitated diffusion
What regulates the movement of cholesterol to mitochondrion?
Steroid acute regulatory protein (stAR)
What regulates steroid acute regulatory protein (stAR) activity and cholesterol processing?
ACTH
How is aldosterone formed in the zona glomerulosa but not the other adrenocortical regions?
Zona glomerulosa contains cells expressing enzymes leading to aldosterone synthesis which are not present in the other regions
What are amine hormones?
Thyroid hormones->small, non-polar molecules-therefore hydrophobic and lipophilic
What is the difference in the number of iodine atoms in thyoxine/tetraiodothyronine (T4) and triiodothyronine(T3)?
T4=4 iodine atoms
T3=3 iodine atoms
Which hormones require carrier proteins?
Steroid and thyroid hormones
What is the effect of hormone carrier proteins?
Increase solubility
Increase half-life
Reservoir in blood
What are the two types of carrier proteins?
Specific binding proteins (eg. thyroid binding globulin (TBG) and cortisol binding globulin (CBG))
Non-specific binding proteins (eg. albumin-loose binding->binds aldosterone)
What is the site of action of hormones?
Protein/peptide=cell surface receptors
Steroid=intracellular receptors in cytoplasm/nucleus-hormone-receptor complex binds to HRE (hormone response element)
