The Cellular Basis of Hormone Action Flashcards
Endocrine System Def.
Secretes hormones. Coordinates slower but long acting responses. Eg growth, reproduction and behavior
Hormone Def.
Biochemical messenger, released from endocrine gland. Impacts gene expression and state of proteins
Feedback Def.
How hormones are regulated in endocrine system
Negative Feedback Def.
Hormone conc. is kept in a narrow range
Positive Feedback Def.
Amplifies hormone response
Endocrine Signalling Def.
Hormones act mainly on distant sites but can also act locally (both paracrine and autocrine)
Paracrine Def.
Target cells are adjacent to secreting cells (hormone travels)
Autocrine Def.
Hormone acts on secreting cell (hormone doesn’t travel)
Factors that receptors shape and frequency on cell membrane influence
Type of substrate and potency of substrate on cell
Hormone Formation (outline)
Stimulus received + processed by endocrine gland. Hormones secreted into blood. Carried to receptors with specific binding site
Examples of hormones altering cell conditions
Opening closing membrane channels (permeability), gene activation/suppression (functional protein expression), enzyme activation/deactivation, secretory products (suppression/induction) , cell division
Hormone Action (outline)
Receive stimulus, hormone secretion, receptor binding, tissue condition change and feedback
2 Main Factors Effecting Cellular Response Degree
How hormone’s delivered and receptor’s/tissue’s status
Hormone Delivery Considerations
hormone synthesis/secretion rate, target cell proximity, transport proteins dissociation constants (hydrophobic hormones), inactive to active conversions and liver/kidney clearance rate
Receptor/ Tissue Status Considerations
Receptors density + state of occupancy, receptor’s hormone affinity and receptor desensitization
Hormone Classification Categories
Chemical composition, solubility, binding site location, receptor basis
Chemical Compositions of Hormones
Steroids, peptides and glycoproteins
Solubility of Hormones
Hydrophobic vs Hyrdrophillic
Binding site locations
Intracellular vs cell surface
Receptor bases
G-protein + second messengers and kinase
Steroid Hormone Outline
Derived from lipid cholesterol, hydrophobic (non water soluble) and thus bind to transport proteins in blood. Eg testosterone
Amine Hormones Outline
Derived from trytophan and tyrosine (amino acids). Can be hydrophillic or hydrophobic. Eg thyroxine
Peptide/ Protein Hormones
Multiple amino acids forming chain. Peptides = short chain. Protein is polypepptide chain
Hydrophobic (Lipophilic) Hormones Outline
Non-water soluble. Bind to transporter proteins in circulation
Hydrophillic (/lipophobic) hormone outline
Water soluble. Travel independently in circulation
How hydrophilic hormones bind to cell
Extracellular. Can’t move through lipid bi-layer. Creating a signalling cascade controlled by a second messanger
How hydrophobic hormones bind to cell
Intracellular. Can diffuse across lipid bi-layer. Binds to DNA segment causing transcription
Steps of hydrophobic hormone binding
Diffusion, Binding, Translocation, Hormone Response Elements, delta expression
Hydrophobic Hormone Response Elements (HRE)
Receptor with hormone binds to HRE on DNA
Delta Expression Def.
Binding derives change in mRNA and resulting protein expressions
Hormone Response Elements
Regions of DNA, consensus sequence and close to initiation (transcription) siteHREs associate with activated receptor and nuclear receptor proteins. More complex
Hydrophilic Hormones Outline
Binding, Intracellular Signaling, PKA activation and Phosphorylation
How message from Hydrophilic crosses membrane
G-protein receptors
Intracellular Signaling
G proteins activate adenylate cyclase (converts ATP to cAMP(cyclic adenosine mono phosphate)). Propagates signal through cell
PKA (protein kinase A) Activation
cAMP targets and activates protein kinase A within cytosol
Phosphorylation
PKA triggers selective phosphorylation of cellular proteins eg nuclear transcription factors
Phosphodieterase Outline
Activated by protein kinase A. Deactivates cAMP forming negative feedback loop for phosphorylation
Examples of 2nd messangers
cAMP, calcium, cGMP
Ligand-Activated Protein Kinase Activity
Aggregate and phosphorylate eachother at specific tyrosine residues in cytoplasmic tail. Propagate signals by autophosphorylation (no 2nd messenger)
Hormone Biological Processes Example
Gene transcription, transporter channels, protein translocation (hydrophilic only), protein modification (hydrophilic only)
Insulin Receptor
Ligand-activated, tyrosine-specific protein kinase
Type 2 Diabetes Cause
Insulin receptor develops insensitivity results in deficient signaling and thus an increase in blood glucose levels
Graves’ Disease Cause
Autoimmune. Antibody binds to thyroid stimulating hormone receptor causing increase thyroid hormone production (hyperthyroidism)
Enzyme Linked Immuno-Sorbent Assay (ELISA) Outline
Measure hormone concentrations in blood. The darker the colour in the say = the higher the conc. of hormone. Used in diagnosis and pregnancy tests. Can be quantative (exact conc) or qualative (yes/no)