Overview
This lecture explains how hydrophilic (water-soluble) hormones affect target cells through second messenger systems, focusing on the phospholipase C (PLC) pathway, and reviews key points about hormone delivery, signaling mechanisms, and medical implications.
Hydrophilic Hormones: Basic Properties
- Hydrophilic hormones are usually derived from amino acids or peptides.
- They travel easily in blood plasma but cannot cross cell membranes due to their polarity.
- These hormones bind to extracellular receptors on target cells.
Second Messenger Systems
- Hydrophilic hormones require second messenger systems to transmit signals inside the cell.
- The cyclic AMP (cAMP) system is one such pathway (reviewed briefly).
- Another pathway utilizes phospholipase C (PLC) and calcium ions.
The PLC/IP3/DAG Pathway
- The hormone binds to an extracellular receptor, activating a G protein.
- Activated G protein triggers PLC instead of adenylyl cyclase.
- PLC acts as "scissors" to cleave PIP2 (phosphatidylinositol 4,5-bisphosphate) into DAG (diacylglycerol) and IP3 (inositol trisphosphate).
- IP3 causes the release of Ca²⁺ ions from the smooth endoplasmic reticulum.
- Calcium ions can act as third messengers, further propagating the signal.
- DAG and IP3 activate protein kinase C, which phosphorylates target proteins (e.g., on serine or threonine).
Hormone Signaling and Amplification
- One hormone molecule can cause the production of many second messenger molecules, amplifying the response.
- Protein kinases (like protein kinase C) modify proteins to activate or deactivate cellular processes.
- The signaling cascade ensures efficient and regulated cellular responses.
Medical Relevance & Drug Delivery
- Hydrophilic hormones (e.g., insulin, epinephrine) must be injected or inhaled, not taken orally, to avoid digestion in the stomach.
- Adrenaline's effects depend on whether it's released locally (short term) or enters the bloodstream (systemic, longer lasting).
- Asthma inhalers now use albuterol (an epinephrine derivative) instead of adrenaline for fewer side effects.
Key Terms & Definitions
- Hydrophilic hormone — hormone soluble in water, cannot cross cell membranes.
- Second messenger — molecule inside cells that transmits signals from receptors to targets.
- G protein — a protein that relays signals from activated receptors to enzymes.
- Phospholipase C (PLC) — enzyme that cleaves PIP2, producing second messengers DAG and IP3.
- PIP2 — phospholipid that is split by PLC to produce second messengers.
- DAG (diacylglycerol) — activates protein kinase C.
- IP3 (inositol trisphosphate) — releases Ca²⁺ from the smooth ER.
- Protein kinase C — enzyme activated by DAG and Ca²⁺, phosphorylates proteins.
- Amines — hormones derived from amino acids, some act as neurotransmitters.
Action Items / Next Steps
- Draw a flowchart of the PLC/IP3/DAG pathway to visualize hormone signaling.
- Review major hydrophilic hormones and their second messenger mechanisms.
- Read the next section on lipophilic hormone signaling.