SIGNALLING MOLECULES Hormones

Signal=Ligand

Signaling Molecules The endocrine and nervous system transmit messages by releasing signaling molecules that act by attaching to specific receptors .(enzyme- like protein molecules) in the membranes of target cells. A target cell is one that has the appropriate receptor for a particular signalling molecule . Some target cells may be widespread throughout the body (as in the target cells for thyroxine) or may be located in a particular place (as in the hormones released from the hypothalamus that act on certain cells in the pituitary gland).

Chemical nature of hormones The chemical nature of a hormone influences the way in which it interacts with it target cells. There are three different kinds of hormones based on their chemical structures _ amino acid hormones _ peptide and protein hormones _ steroid hormones

Hydrophobic = Lipophillic Hydrophillic = Lipophobic

Types of hormones Hydrophilic Amino acid & peptide - Soluble in water - Unable to pass through membranes - Require 2nd messenger molecule to transfer messages - Dissolves into the blood to reach target cell Hydrophobic Steroid Hormones - Insoluble in water - Able to pass through membranes - Do not require second messenger hormone - Require a carrier protein to reach target cell

Hydrophobic & hydrophillic signals Hydrophillic signalling molecules Neurotransmitters Growth Factor Hormones Insulin Hydrophobic signalling molecules/Lipophilic Steroid Hormones Thyroid Hormones

Where are the receptors for hydrophobic signalling molecules? These hormones are able to pass directly through the plasma membrane and bind their specific receptor (intracellular) within the cytoplasm of the target cell. These molecules require a carrier protein for transport in the blood as it is water based. Steroids Cortisol Testosterone Oestrogen Progesterone Eicosanoids (derived from fatty acids) Prostoglandins Lipid soluble hormones leave the secretory cell by simple diffusion Target cell Intracellular receptor Insoluble in blood plasma so needs water-soluble carrier molecules to transport them around the body. Once synthesized, steroid hormones pass into the bloodstream; they are not stored by cells, and the rate of synthesis controls them.

Hydrophobic signals bind to intracellular receptors Steroid hormones regulate gene expression. 2. 1. Steroid Hormone moves across the plasma membrane. 1. Ligand-Receptor complex 2. Signal binds with intracellular protein receptor. 3. 3. The ligand-receptor complex moves into nucleus to bind with DNA to regulate gene expression. 4. Proteins are the products of gene expression. Transcription 4. Translation

Receptors for hydrophillic signalling molecules Small Peptides Vasopressin Protein hormones made up of chains of amino acids. Some with carbohydrate side chains. Insulin Glucagon Growth Hormone Luteinizing hormone Neurotransmitters Hormones derived from specific amino acid molecules; tyrosine and tryptophan Adrenaline Dopamine Water soluble hormones are unable to pass through the cell membrane. As a result they bind with specific receptors on the surface of cell membrane of the target cell. They are all amino acid based molecules but vary in the number of amino acid residues. Water soluble hormones are stored in vesicles and secreted from the cell by exocytosis Secretory Cell Soluble in blood plasma Receptor on plasma membrane Target Cell

Types of plasma membrane bound receptors (activated by hydrophilic hormones) Ion Channel Receptor G protein-coupled Receptor Tyrosine kinase linked Receptor Milliseconds Seconds Can take hours G-Protein & Tyrosine Kinase receptors stimulate other molecules (secondary messengers) in the cytoplasm in what is called the ‘signal transduction pathway’ A common secondary messenger is called cAMP – cyclic adenosine monophosphate Causes a shape change that opens the channel so ions can enter or leave the cell. Eg. Acetylcholine at nerve/muscle junctions. activates a G protein which activates or inhibits an enzyme or modulates an ion channel that generates secondary messengers. Eg. Receptor for glucagon causes a shape change that activates enzymes within the cell Eg. Human Growth Factor

Signal Transduction Fatty Acid based Hormones (lipid solu ble) Protein based Hormones (water soluble)

The Signal Transduction Pathway 1. The Signal Transduction Pathway 2. Applying the stimulus response model. 1.Signal binds to receptor molecule. 2. Receptor molecule changes shape of confirmation. 3. Initiates a molecular cascade of secondary messenger molecules to an effector molecule. 4.Effector initiates the cellular response. 3. Responses Enzymes activated or deactivated Genes switched on or off Protein channels in plasma membrane opened or closed Vesicles moved to plasma membrane so content can be released by exocytosis 4.

How is the signal amplified? Each successive step in the signal transduction pathway may activate multiple molecules in the next step. Pathways may branch to produce multiple responses from the initial signal. This is why small amounts of signalling molecules can produce a significant response or even multiple responses. Relay runners pass the baton onto more and more runners This increase in molecules becoming involved in the process is called the molecular cascade

Four Cellular Responses Effector molecules bring about the cellular response. Activate or inhibit enzyme action. Regulate the expression of proteins by switching genes on or off. Move transport vesicles to the plasma membrane to secrete cellular products. Open or close protein channels. Once a signalling molecule has delivered the message to a cell and the cell response is initiated, the signalling molecule is degraded by enzymes.