330 likes | 521 Views
Cell Growth, Regulation and Hormones . Levels of Cell Regulation. Intracellular Within the individual cells Local Environment Cells response to its immediate environment, including presence of other cells Locally acting factors from cells Extracelular Matrix Systemic Regulation
E N D
Levels of Cell Regulation • Intracellular • Within the individual cells • Local Environment • Cells response to its immediate environment, including presence of other cells • Locally acting factors from cells • Extracelular Matrix • Systemic Regulation • Provides for integration of activities of cells distant from each other • Endocrine system • Nervous system • Considerable overlap between these.
Intracellular Regulation Regulatory Enzyme Covalent modification Can be positive or negative phosphorylation is common. Substrate Product 2 Phosphatase Enzyme Reverses regulatory enzyme effects Enzyme 2 Non-covalent Modifiers Product
Endocrine Signaling Endocrine Cell Target Cell Receptor Signal Hormone Blood Stream
Paracrine Signaling Signaling Cell Target Cell Receptor Signal Diffusion Hormone
Autocrine Signaling Hormone Signal Receptor
Signaling Juxtacrine Receptor Target Cell Signaling Cell Signal Membrane-bound Hormone
Signal Integrin Signaling Target Cell ECM Component Integrin Basement Membrane
Example Growth Factors Autocrine Stroma Epithelium TGF TGF Paracrine PgE2 Cell Division
PgE2 Signaling Inactive Inactive Receptor Adenylate Cyclase GDP G Protein Inactive R R R = Regulatory Subunit Protein Kinase A (PKA) C C C = Catalytic Subunit
PgE2 Receptor Activation PgE2 Receptor Adenylate Cyclase GDP GTP ATP G G G GTP cAMP cAMP PKA-C PKA-R PKA-C cAMP PKA-R Phosphorlation of substrates Altered enzyme activities
PgE2 Receptor Inactivation PgE2 Receptor Adenylate Cyclase GDP G G G G G has GTPase Activity cAMP PKA-R Phosphosphatase PKA-R PKA-C PKA-C AMP
Matrix Metaloprotease Secretion degrade basement membrane Secrete Basement Membrane Growth Factors Secrete Extracellular Components
Cell Division How does the mammary gland “know” when to stop growing?
Hormone Inactivation Protease Degradation Active Hormone Degraded Hormone Binding Protein Interaction Binding Protein Inactive Hormone
Receptor Downregulation Internalized Receptors Internalization Degradation x Modification x x x often de-phosphorylation Signals x Signals x Hormone Signals Receptor
Inhibitory Pathway Concurrently Stimulated Stroma Epithelium TGF TGF Cell Division
Hormone • Chemical substance • There are many diverse substances • Produced in one organ • Many (all?) organs produce hormones • Transported via blood • Now recognize other pathways too • To a distant organ • May not be very far • Where it modifies its function • Many different functions can be regulated by hormones
Hormone Chemistry Proteins Insulin Glucagon Growth Hormone Prolactin ACTH Oxytocin Calcitonin Parathyroid hormone Most Growth Factors Glycoproteins LH FSH TSH PlacntalLactogen Steroids Estrogens Progesterone Testosterone Aldosterone Glucocorticoids
Amino Acids Thyroxin T3 Catecholamines Epinephrine Norepinephrine Prostaglandins
Binding Equilibrium H + R HR Noncovalent interaction. In equilibrium when forward and reverse rates =. Equilibrium calculations similar to general chemistry. Kd = concentration when 1/2 receptors occupied. ED50 = concentration when half-maximum responses reached. NOT necessarily = Kd.
Hormone Binding Kd (50% receptors occupied)
Hormone Response ED50 (Half-Maximum Response)
Higher Brain Environment Positive Neural Impulses Hypothalamus Negative TRF Anterior Pituitary TSH Thyroxine Body Metabolism Thyroid Feedback
Other Inhibitory Mechanisms • Hormone Degradation • Most hormones are degraded with a half-life of 1-30 minutes • Time for 1/2 of hormone to be degraded • Receptor Down-regulation • Decreases response to hormone • Stimulation of inhibitor production • Hormone can increase production of a factor that inhibits its production or action • Ex: mammary growth factors increase production of growth inhibitors as a feedback loop.