L6: Action of Hormones & Thyroid metabolic hormones and adrenocortical hormones Flashcards
two factors that determine clearance of hormones in the blood
rate of secretion into the blood and rate of removal from the blood
Metabolic clearance rate
rate of disappearance of the hormone from the plasma/concentration of the hormone
types of hormone receptors based of location
- In or on surface of cell membrane
- In the cytoplasm
- In the cell nucleus
What is one important aspect of the receptors on target cell?
the number of different receptors which is constantly changing
Ways in which receptors can be down-regulated
- inactivation of some receptor molecule
- inactivation of intracellular protein signalling molecules
- temporary sequestration of receptor inside the cell
- destruction of receptors by lysosomes after internalization
- decreased production of receptors
Ways in which receptors can be up-regulated
- stimulating hormone induces more receptors and/or signalling molecules
Types of hormones based on how they interact with cells (i.e. types of hormone receptors)
- Ion channel-linked receptors
- G-protein-coupled hormone receptors
- Enzyme-linked hormone receptors
- Intracellular hormone receptors
What does activation of ion channel-linked receptors cause?
causes structural change in receptors either opening or closing channel for K, Na, or Ca
What is the most common way in which ion channel-linked receptors are used?
they are used indirectly by exerting their action on G-protein couples receptors which then activate ion channel-linked receptors
In what state does the G protein need to be in in-order for alpha subunits to bind to GDP? What about GTP?
when G-protein is active alpha subunits bind to GTP, and when it is inactive, alpha subunits bind to GDP
How do G-proteins work?
Ligand hormones binds to extracellular component of receptor changing the conformation of the receptor and activates the G-protein inside the cell. This will then induce a signal causing ion-channel to open or close. The alpha binding to GTP is what causes activation of ion-channel receptors.
Obesity
characterized by excessive amounts of leptin
Leptin
- cytokine-like molecule produced in white adipose tissue (WAT)
- example of enzyme linked hormone receptor
Primary role of leptin
- maintain body weight homeostasis by inhibiting food intake and stimulating energy expenditure
How is body weight maintained?
- through the use of leptin
- leptin is released by adipocytes (fat sites), enters the circulation and reaches hypothalamus by going through blood-brain barrier
- leptin inhibits appetite through hypothalamus, induce lipolysis in white adipose tissue and thermogenesis in brown adipose tissue
Lipolysis
- breaking down of lipids in white adipose tissue
What happens to obese subjects?
- leptin fails to inhibit appetite, unable to induce lipolysis, or unable to allow for thermogenesis to occur on brown adipose tissue
Describe how adenylyl cyclase cAMP serves as an example of secondary messenger system?
- activated G-protein stimulates adenylyl cyclase (membrane bound enzyme)
- alpha subunit of G-protein is in its active state because its bound to GTP, which is now binding to adenylyl cyclase
- adenylyl cyclase catalyzes the conversion of small amount of ATP within the cell into cyclic AMP
- this conversion of ATP to cAMP will activate cAMP dependent kinase which will then be able to phosphorylate specific proteins leading to cell’s response to hormone
Describe how cell membrane phospholipid serves as an example of secondary messenger system?
- hormone binding activates a transmembrane receptor that’s going to activate enzyme phospholipase C
- phospholipase C will break down PIP2 into two secondary messenger products - IP3 and DAG
- IP3 mobilizes Ca from intracellular stores causing smooth muscle contraction and changes in cell secretion
- DAG activates protein kinase C (PKC) which will phosphorylate a larger number of proteins leading to cell’s response
Describe how calcium-camodulin serves as an example of secondary messenger system?
- operates in response to entry in calcium (which can happen in two ways:
1. Change in membrane potential that opens voltage-gated Ca channels
2. Hormone interacts with membrane receptors that open calcium channels - Ca cannot bind to calmoduim if Ca is in low concentration - has to be at a certain level
- calcium binds to 4 sites on calmoduim causing a conformational change
- this causes activation or inhibition of protein kinases within the cell
