Endocrine axis Flashcards
What 3 systems are the main regulators of homeostasis?
- parasympathetic system
- sympathetic system
- endocrine system
What is the main action of pharmaceuticals?
Manipulating the endocrine system (or intracellular signalling pathways regulated by it)
What concentrations are signalling molecules most active and why?
They are active at very low concentrations due to dilutions
What two scientists found secretin?
What secretes this compound?
Bayliss and Starling found secretin
S cell respond to an acid and then they secrete secretin
Give an example of an endocrine pathway and explain it?
Renin-angiotensin-aldosterone system
- Renin cleaves angiotensin and forms angiotensin I
- Angiotensin I cleaved by ACE
- Angiotensin II produced form this
- Angiotensin II roles;
- Activates the sympathetic NS which causes constriction of blood vessels
- Binds to receptors in the later part of loop of Henle and Collecting duct drives absorption of NaCl and excretion of K+
- carried to adrenal gland and on adrenal cortex there’s glomerular cells which release aldosterone (hormone)
- AII causes vasoconstriction of arterioles
- And causes pituitary gland to secrete ADH
- ADH involved in vasoconstriction and absorption of water in collecting duct
Whats the most important thing for a hormonal system?
The specificity of receptor for the hormone
What are receptors only expressed on?
The defined (reacting) cells
Tell me about the affinity of the hormone for its receptor?
Very high affinity of the hormone for its receptor
Kd= 1x1012 M
Hormone concentrations as low as pg/ml
What type of system is a hormonal system?
- integrated amplification system
- Protected transfer system (many hormones transferred bound to a carrier protein e.g. albumin especially if hydrophobic)
H-CPr <–> H+CPr
(only free hormones bind to its receptor and causes effect)
CPr= carrier protein
What does the overall effect of a hormone depend on?
- concentration of free hormone
- number of receptors present on cell
- affinity of hormone for its receptor
- efficiency of amplification
- stopping signal
What are the three main hormone families?
Give examples for each
Which ones are water soluble/ water insoluble?
1. Amine derived hormones: Water soluble
- from tyrosine and tryptophan
- example: Catecholamine and thyroxine
2. Peptide hormones: Water soluble
- small peptide hormones (TRH and ADH/ vasopressin)
- Protein hormones (insulin and growth hormone)
- Glycoprotein hormones (Luteinizing hormone, thyroid-stimulating hormone)
3. Lipid and phospholipid hormones: Water insoluble
- Eicosanoids (prostaglandins, prostacyclines, thromboxanes or leuktreins)
- Steroid hormones derived from cholesterol (testosterone and cortisol).
- Calcitriol Vit D) is a sterol derived hormone
Tell me the ratio of most hormone-receptor reaction?
1:1
The stronger the reaction ie. the most in the HR state, the smaller the ration of free to bound
Draw a Scatchard plot and a general curve graph to show the binding of receptors to specific signals.
Annotate the graphs of what they show?
Is the reaction between a receptor and a hormone, reversible or irreversible?
What is used to measure the affinity of the reaction?
The interaction of receptor and hormone is reversible, and the ease of separation Kd is a measure of its affinity
How is a maximal biological response achieved in hormone, receptor interactions?
But maximum biological response is achieved at concentrations of hormone far lower than required to occupy all the receptors on the cell (Bmax) or even 50% (Ka) due to amplification
Eg. Insulin stimulates maximum effect in adipocytes with 2-3% of receptors bound
LH stimulates maximum testosterone production in Leydig cells with 1% of receptors bound
The concentration of hormone needed for maximal response is an indicator of what?
The sensitivity of the system
Whats the liminting step of receptor binding reactions?
why?
The limiting step is hormone binding
as the amplification steps following receptor binding, (second messengers or phosphorylation cascades) are very efficient
Give 6 examples of secondary messenger system?
Second messenger systems include:
- Adenylate cyclase /cyclic AMP;
- Guanylate cyclase /cyclic GMP;
- Calcium and calmodulin;
- Phospholipase C catalysing phosphoinositide turnover;
- Phosphorylation cascades
- NO
The concentration of hormone seen by target cells is determined by what three factors?
Explain each
1. Rate of release
- synthesis and secretion of hormones are the most highly regulated aspect of endocrine control
- controlled by positive and negative feedback
2. Rate of delivery
- the blood flow from the endocrine organs to a target organ or group of target cells
- high blood flow delivers more hormones than low
- Consider if there are carriers involved
3. Rate of degradation and elimination
- Hormones, have characteristic rates of decay, (metabolized and excreted)
- Shutting off secretion of a hormone with a short half-life causes circulating hormone concentrations to drop rapidly, but if a hormone’s biological half-life is long, effective concentrations persist after secretion ceases.
Whats the role of carrier proteins?
- protect from degradation
- prevent being in active form
- specific degrading enzymes for some hormones
How are the levels of hormones measured?
Explain each?
1. Radio-immune assay
- not done anymore but can be done artifically in a lab
- measure amount of radioactivity
- sensitive to 1x10-14 M
2. ELISA
- Sensitive to 1x10-12 M
Shows relative sizes of units
What are the 2 type of hormones?
Note which receptors are specific to those types of hormones?
Do they require secondary messengers?
Whats the main function of the primary endocrine organs?
Main function is to secrete Hormone(s)
Whats the function of the secondary endocrine organs?
secrete hormones as a secondary function
Name the primary and secondary endocrine organs
Classically what are endocrine (ductless) glands derived from?
epithelial but also from neurons (neurohormones) and isolated cells (diffuse cells-intestine)
Name other cells which can be primary endocrine organs that dont have an epithelial origin?
- muscles cells
- fat cells
- bone cells
- immune cells- cytokines not considered hormones
Need to know something about everything on this list by the end of the module
Draw a typical feedback loop controlling ‘A’
Whats the normal Ca2+ level in adults?
2.25 - 2.75 mmol/L
The range is wider in children
Control of extracellular Ca2+