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+
What substance causes the increase in Ca2+ and what causes the decrease in Ca2+?
Calcitonin causes the decrease in Ca2+
Parathyroid hormone causes the increase in Ca2+
What are the 2 types of hyperparathyroidism?
What does each type cause?
Hyperparathyroidism
1. Primary- tumour of parathyroid (gives high serum Ca2+)
- Moans
- Stones
- Groans
- Bones
2. Secondary- caused by renal failure and loss of Ca2+ by kidney, low serum Ca2+
- causes increased parathyroid activity
What does hypoparathyroidism cause?
- autoimmune diseases
- latrogenic
- Low serum Ca2+
Tell me about Hypercal?
- fatigue
- depression
- memory loss
- bone aches
- raised blood calcium (primary)
Tell me about hypocal?
- Tingling extremities (nervous)
- Pain in the face, legs, and feet
- Muscle cramps
- weakened tooth enamel
- muscle spasms called tetany (can lead to spasms of the larynx, causing breathing difficulties)
- Convulsions (seizures)
- Tetanic contractions
- Chronic changes
What hormones are used to regulate blood calcium levels?
How do they act?
What type of feedback cycle is used?
The regulation of blood calcium levels is controlled via the parathyroid and calcitonin hormone.
They act antagonistically
Uses a negative feedback cycle
What is hypocalcaemia and what is this often called by farmers?
What is it caused by?
Loss of Ca2+ ions in the milk due to the high lactation that the blood plasma levels of Ca2+ drops- the parathyroid is unable to meet the metabolic demand (milk fever)-
tumour related or due to renal failure
What do the following all control:
- insulin
- glucagon
- parathyroid hormone
Direct feedback control systems
What are other hormones (sex hormones, corticosteroids, thyroid hormones and growth hormones) all organised by?
What do these run through?
hormone relays
These run through the hypothalamus and anterior pituitary gland (complex control systems) also, sensory inputs are also involved Neuroendocrine system
Tell me the different pathways that tropic hormones are released by?
A B
The hypothalamus –> Pituitary –> Adrenal axis
The hypothalamus –> Pituitary –> Gonadal axis
The hypothalamus –> pituitary –> Thyroid axis
What are primary tropic factors released by?
The hypothalamus (A) which feeds onto the anterior pituitary which in turn produces secondary tropic hormones (B)
Tell me the relationship between Growth hormone and prolactin
They fit in similar systems but with modifications
Where is oxytocin and ADH released by?
What do they target?
They are released by the posterior pituitary gland (neurohypophysis) an extension of the hypothalamus (neural tissue) and are NOT tropic hormones
They act directly on target organs
What are tropic hormones?
Have other endocrine glands as their targets and cause hormone release
What are non-tropic hormones?
they directly stimulate target cells (insulin, calcitonin, ADH)
What are Trophic hormones?
Cause a growth effect, hyperplasia or hypertrophy, on the tissue it stimulates
When can tropic hormones also be trophic hormones?
If they make endocrine glands larger
How many hypothalamic nuclei are there?
Give 2 examples?
16
Example:
- Paraventricular nuclei
- Supraoptic nuclei
What does the hypothalamus coordinate?
inputs from CNS and carried in the blood stream
What does the hypothalamus regulate?
- body temperature
- hunger
- thirst
- fatigue
- circadian rhythms
i.e. body metabolism
What dot he hypothalamus have contact with?
It is in intimate contact with the pituitary via direct contacts and an interconnected blood supply
What are the hypothalamic inputs?
The central nervous system
- The brainstem autonomic zones
- the olfactory bulbs
- cerebral cortex
What does the hypothalamus respond to?
Tell me abit about each
1. Light
(day length and photoperiod) regulating circadian and seasonal rhythms
2. Olfactory stimuli
including pheromones
3. Autonomic inputs
Neural transmitted information arising in particular from heart, digestive and reproductive tracts
4. Endocrine inputs
Steroids, including gonadal steroids and corticosteroids (feedback)
Plasma concentrations of glucose and osmolarity etc and hormones involved in their regulation leptin, angiotensin, insulin, pituitary hormones
5. Cytokines
from immune system and toxins from invading microorganisms – responds by increasing body temperature (fever)
6. stress
from cerebral cortex
Hypothalamic outputs are what type of hormones?
Neuropeptide hormones
What are hypothalamic hormones secreted by?
By neurons in the hypothalamic nuclei- their nerve endings run into the specialised local blood circulation in the hypothalamus which drains into the anterior pituitary (epithelial)
OR
Other hypothalamic axons run down into the pituitary forming the posterior pituitary (neuronal) these release their neuropeptide hormones to the systemic
Label the following structures
Label the following structures
Tell me about each of the following involved in circulation…
- anterior pituitary
- epithelial cells
- neural
Anterior pituitary- highly active- producing hormones
Epithelial cells – lots of RER – hence stains darker
Neural – axonal endings – myelin from oligodendrocytes- (lipid) stains pale
What are the different forms of capillaries?
- continuous
- fenestrated
- sinusoid
Label the capillary structures
Where are continuos capillaries generally found?
- fat
- muscle
- nervous system
Where are fenestrated capillaries usually found?
- intestinal villi
- endocrine glands
- kidney glomeruli
Where are sinusoid capillaries usually found?
- liver
- bone marrow
- spleen
Name the seven releasing/ inhibitory hormones which are made in the hypothalamus and released in pulses?
what type of molecule are they?
What do they act on?
- Thyrotropin: releasing hormone (TRH) -induces TSH release: peptides
- Corticotropin: releasing hormone (CRH)- induces ACTH release: peptides
- Gonadotropin: releasing hormone (GnRH)-induces Follicle stimulating Hormone and Leutinising Hormone release: peptides
- Growth hormone: releasing hormone (GHRH): peptides
- Growth hormone: inhibiting hormone- Somatostatin (GHIH): peptides
- Prolactin: releasing hormone (PRH): peptides
- Prolactin: inhibiting hormone (PIH): Dopamine
Each act on a specific group of cells in the anterior pituitary
What do the following respond to and form?
- Thyrotropes
- Corticotropes
- Gonadotropes
- Somatotropes
- Lactotropes
1. Thyrotropes
Respond to TRH
form Thyrotropin (5-10%)
2. Corticotropes
Respond to CRH
form ACTH (20%)
3. Gonadotropes
Respond to GnRH
form FSH, LH (5%-10%)
4. Somatotropes
Respond to GHRH/ somatostatin
form GH (40%)
5. Lactotropes
Respond to PRH/PIH
form Prolactin (5-10%)
What do the following releasing cells
1. Produce
2. Target
3. Effect
releasing cells
- Corticotropes
- Somatotropes
- Thyrotropes
- Gonadotropes
- Lactotropes
Whats the mechanism of control in the endocrine system ?
Tell me about the feedback loops?
Tell me how the levels of different hormones are effected by tumours?
What amino acids differ in ADH and oxytocin?
What is ADH (Vasopressin (american)) produced by?
axons from paraventricular/ supraoptic nucleus
What does ADH regulate?
Blood pressure and water balance
What the secretion of ADH induced by?
- Central osmoreceptors (close to hypothalamus), increased osmolarity
- Reduced plasma volume (blood pressure monitors) triggers baroreceptors in aortic arch and carotid sinus which signal via vagal nerves to CNS
- Angiotensin II (protein)
Whats the action of ADH?
- G coupled receptors (7 pass receptors)– collecting duct epithelial cells and endothelial cells
- Acts on collecting duct to insert aquaporin 2 (with no ADH this is almost 100% impermeable to water)
- Stimulates NaCl uptake in ascending limb of loop of Henle (needed for above as water moves with it back into body)
- Causes –vasoconstriction, increases peripheral vascular resistance and lowers vessel volume
- increases water retention and blood pressure
The following diagram shows how ADH increases water retention and blood pressure
Whats oxytocin produced by?
Paraventricular/ supraoptic nucleus
Whats the action of oxytocin?
- Contraction of myoepithelial cells in mammary gland for milk release
- Contraction of uterus during birth
- Example of a +ve feedback loop
- CNS effects bonding
What does the pars intermedia produce?
What does it induce?
produces Melanocyte stimulating hormones (MSH)
induces melanocytes to form melanin
(ACTH is also formed from the same precursor as MSH but cleaved differently)
Shows level of hypothalamus
