Endocrinology - Cell Biology
What are Juxtacrine Signals
These are signals betwene cells that have a direct contact with each other, there are many different jucntions needed between the 2 cell membranes when in contact with each other
What are CAMS
These are cell adhesion molecules and act as junctions between the 2 cell membrane when they are in contact at juxtacrine signals
They make up the communicating junction, the anchoring junction and the occluding junctions
What are the non-specialised contact CAMS
Notch and Selectins are non specialised and the specialsied for membrane contact are called Cadherins + Connexins and then Occludin and Claduin Proteins
These interactions can be either homophilic or heterophilic
What are communicating junctions
These are gap junctions like in a synpase so only molecules less than 1000 dalton can pass
They are a direct link from 1 cell cytoplasm to the other cell cytoplasm
How are connecting junctions made
By grouping of 6 connexin molecules that form connexons
There are 14 types of connexin and if all 6 are the same then homeric and if not then it is heteromeric
You get 1 connexin from each cell that will align and able to form a pore between the 2 cell membranes
How is a connecting junction pore regulated
The proe can be regulated so is not always open, this is good for apoptosis due as this will cause high levels of Ca2+ that can cause DNA breakdown so important to close the pores so Ca2+ doesnt enter the other cells. Allows only the programmed cell to die.
Also important in the eye due to dopamine released at bright light in order to regulate the spread of the signal in eye cells, so at low light pores open in the Rods and at high light they close between the Cones
What are Tight Junctions
Are able to form seals between cells, and so the more point of attachement the tighter the tight junction will be
What do tight junctions do
Act as an impermeable bond between the cells
Maintain the osmotic varience due to limit paracellular permeability
Molecules cant pass through from the apical or the basolateral side due to cause lumen seperation
Compartmentalise the membranes of the 2 cells by causi9ng different polarity in the membranes so things cant pass from the apical to the basolateral as are 2 different compartments
What are Tight Junctions made of
Made up of transmembrane proteins that pass through the membrane 4 times
These are called Claudins and Occludins and are both momotypic so only intercat with itself
The more layers there are of them then the tighter the tight junction
Where are tight junctions found
They are found in blood vessels where they are not tight due to want the movement of nutrients between the blood and the tissue
Found much tighter round the brain and testis to prevent toxin entering and form the brain barrier
They are signalling centres due to signal cascades and gene expression
What are Anchoring Junctions
These are used to strengthen the link between the cells in a juxtracrine signal
There are actin cytoskeleton adherins used and also Keratin desmosomes used
They both contain Cadherin that cross the cell membrane
What are Cadherins
These are Ca2+ dependent for cell to cell anchoring, when Ca2+ present they undergo a conformational change so they extend outwards to the other cell membrane to then interact with other cadherins of the same type exteneded from the other cell
If no Ca2+ then cadherin dont change shape and the cells will seperate from each other due no cadherin dimer formed to extend outwards
How are Cadherins signalling centres
This is as they concentrate Kinases and their Substrates
Important for the WNT pathway needed for cell divison regulation due to resevoir for B-catenin
What are the types of Cadherins
In actin adherin junction get classical cadherins which are : E,N,P and VE
In keratin desmosomes get atypical cadherins that are desmoglein and desmocollin
Why is it important that Cadherin are homophilic extreme
Used to drive cell sorting by dissociate embryonic tissues and the tissue reform based on cadherin expression which is important for development
What is Notch Signalling
Type of non-specialised contact
In 1 cell there is a,oigand called delt and the receptor on the other cell called notch that are able to intercat together and cause an effect
How does Notch Signalling work
Notch protein made in the golgi and ER and in the golgi have an enzyme that cleave notch and then cleaved bit held by non-covalent intercation to original bit
If delta expressed by nearby cell then causes shape change so the orginal big notch part will seperate
Left with smaller bit in the membrane that also is cleaved and cause conformational change so it can then enter the cell and migrate to the nucleus
In nucleus bind to RUPSUH protein to turn off gene expression
What are Selectins
These arew Lectins which are sugar bidning proteins where they bind to sugars on the cell membrane and can cause cell attachment to tissues
During inflamtion epithelial cells epxress selectins on cell surface so then leuococytes are binded to so then inflammed region is flooded with white blood cells to fix it
What are the 2 types of Cell matrix
Mesincinal Matrix found in the bone, cartilage, fibrolblasts, loose connective tissue
Basement membrane matrix is on the basal surface in epithelium cells and kidneys
Why is the extracellular matirx important
Due to all cells bar white blood cells and tumour cells need to intercat with the extracellular matrix or they will die
What is the structure of the extracellular matrix
College fibre for strength, elastic fibres for resiliance, Linking molecules, Fibroblast
The basal lamina sits below the epithelial sheet at the top of theb loose connective tissue
What is the extracellular matrix used for
Signalling properties due to cell migration
Cell survival
Cell differentiation
and can do this due to having strong tissue borders to strengthen tissue and has a filter effect in the Kindeys
What is Collagen
The most abundant protein in the body, and can provide strength so cant pull arm out of your socket
It exist as fibrils that are laid down in sheets
What is the structure of collagen
Made of a repeat glycene, then 2xlycene and proline then another glycene, that then repeated over and over
It forms a left hand helix due to the small proline
3 of the collagen helic then come togther to form a right-handed super helix which is a collagenj trimer that gets excreted
The trimers are laid down in staggered manner so get a banding pattern dur to areas of different collagen density
How is Collagen secreted
This takes place in the ER to form the monomeric form that then gest glycosylated and hydroxylated at the lycene and the proline
This is important for stabilsation and shift bases to allow covalent bonding dirven by Lysate Hydroxylase
At the N and C terminus no repeating glycene so there is non-collagenous part and at C end form disulphide bridge with 3 of them to form non-collagenous trimer
Upon secretion the non-collagenous trimer cleaved off othersise lead to mutations
What is Elastin
Formed by the polymer Elastin that form fibres when laid around microfilaments of fibrillin that are linked by cross links
Lacks defined structure due to very hydrophobic so get random coils so very elastic
Elastin sysnthesis only as a foetus so limited in later life and reason get wrinkles at older age
What are ProteoGlycans
Able to give compressive strength by water retention
Has a protein core that has highly charged sugars attached to attract water to form water pore gels
Provide large structural support so dont push head through body when pressure applied like jumping
What is the functions of Proteoglycans
resiatnt to compression
The hydrated gel allow motion of nutrients and waste products about isolated cells
High charge density allow for growth factors lile Cytokines
Co-receptoes are inducers for growth
What is Fibronectin
This is loose connective tissue
Made up of dimeric molecule linked by disulphide bridges
Therev are many domains that intercat with specific receptors sihc as Collagen matrix so a link betwen matrix and cell
Can cause cell migration, proliferation and survivla by binding to integrin receptors
What is Laminin
Is in the basement membrane
Is formed as trimer of alpha bgeta and gamma chain and each N terminal is polyermsised to allow interaction between the chain to get network of polymers
Get an alpha helice of each that formed into super helix with 1 from each part chain type
What does Laminim do
Forms self assembling mesh in the basement membrane to interact with proteoglycans, collagen and cell receptors
It is crucial for basement membrane signalling
What are Integrins families
Matrix receptors of laminins and fibronectin
Intergins heterodimicn matrix receptor all specific inntegrins to bind to specific ECM components
What are integrins for
The nucleastion site for actin polymerisation
Allow stable contact betwen contractile machinary and the ECM
Allow cell to make lamellipodia and filopodia which are needed for attachment to the matrix and cell migration
What are Focal Adhesions
When integrins cluster together and bind to specific sequences on the ECM molecuoles
They play a role to anchor the cell to ECM, cell migration and signals from the ECM
A single interaction is low affintiy so weak but lots at the same give high adhesive forces so high affinity
What are Hemidesomosomes
Specific integrins that bind to laminin in the basement membrane to intermediate filmanents
If there is a defect then linkage break from basament membrane
What is a hormome
A signalling molecule that is produced and released into the blood to be carried around the body to a target
They are active at very low concentrations so are very diluted in the blood. They can be produced in some organs to then be used in other organs
What did Bayliss and Starling do
They found that the stomach material in the small intestine causes the pancreas to contract so it can release alkaline fluid to neutralise the HCL in the stomach
There were no nerves involved in the contractions starting in the pancreas
If a lower blood supply to the pancrease then contractions didnt happen and no alkaline fluid will be released from small intestine
What is the endocrine system
Along with the parasympathetic and sympathetic nervous system, it is the main regulator of homeostasis
It will manipulate the endocrine system and is used heavily in pharmalogical interventions such as the Oestrogne pill and to modify blood pressure
What is the Renin-Angiotensisn - aldosterone system
This system is used to regulate our blood pressure so is under high levels of control and allows us to change our blood pressure when is needed to return to the normal- Negative feedback loup
How is our blood pressure detected if it is low blood pressure
There are modified smooth muscle cells in the kidney glomerelus that detect blood pressure as sit on the blood vessel that enter the kidney
If there is low blood pressure then cells in the collecting duct of the kidney montior Na levels in the urea
If at low pressure then more time for kidney to reabsorb the Na so lower Na+ levels in the urine due to more reabsorption.
How is low blood pressure returned to a normal one
Enzyme called Renin is secreted to then cleave angiotensin hormone, this then turn it into angiotensis 1 in theliver
Angiotensin1 is activated by angiotensisn converting enzyme that is on the blood vessle in the Kindey
Then then lead to angiotensisn2 being made which then increases the heart rate and so blood vessels contract
This then causes the Kindey to increase in the absorption of Na+ and Cl- ions along with the excretion of K+ via a pump that works in 3:2 ration with Na+ having 3 absorbed and 2 K+ released
This then cause greater osmotic effect so mroe water absorption to then increase BP
Angiotensin 2 is also activated in adrenal gland so then aldosterone is secreted due to this
Also cause vastroconstriction to up BP
Also ADH production is released so then more aquaporins in collecting duct so then absorb more water so higher BP
Why is High Blood pressure not always good and can be stopped by
Can use Renin inhibitors, ACE inhibitors, Angiotensin 2 receptor is inhibited, Aldosterone inhibitors and ADH inhibitors so keep blood pressure from increasing
What makes a good hormone system
Specificty of a hormone for the receptor so only 1 hormone can intercat with 1 receptoe type
Receptor to only be expressed on reacting cells
Very high affinity of the hormone for its receptor due to low hormone level
Transfer system so that hormone can bind to carrier protein and get to desired target
What makesa a good hormone
Concentration of Hormone
Number of receptors
Hormone affinity for receptor
Amolification efficiency
Stopping the signalling quickly
What are the 3 hormone families
Amine that are Tryosine, Tryptophan and are all water soluble hormones
Peptide Hormones - Small peptide, protein, glycoprotein, thryopid stimulating hormones they are all water soluble
Lipid and Phospolipid hormones - Eicosanoids, Steroids and these are water insoluble
How does a hormone work
A tissue becomes a target for a hormone by expressing a specific receptro for the hormone that are circulating in the blood to bind to the target cells
The hormone -receptor complex is defined as dissociation constant of the complex and so the stronger the interaction the more complexes there are
The Kd is the hormone concentration atv which half be the receptors are bound to a hormone
How do hormones achieve the maxiumum biological response
Achived at a hormone concentration far lower than needed to fill all the receptors due to large amplification
The rate determining step is the hormone binding to the receptor due to amplifiaction is highly efficient
How does the rate of release effect the hormone concentration in cells
Synthesis and secretion of a hormone are the most regulated atage in the endocrine system by postive and negative feedback
How does Rate of delivery effect the hormone concentration in cells
The blood flow from the endocrine organ to the target organ so a high blood flow will deliver more hormones that low blood flow
How does the rate of degradation and elimination effect the hormone concentration in cells
Hormones that have a carrier need to be released from the carrier so it can bind to receptors
Shtting od a secretion of a hormone with short half life causes circulating hormone concentration to drop so signalling pathway will stop
How to measure hormone levels
Radio-labelled hormone and antibody are mixed together to get conjunction and can drop out of the solution
Amount of radio labelled is linked to the amount of hormone binding to the antibody
Add a competitive inhibitor to non-radio labelled hormone that bind to antibody and allow amount of radioactive precipitate is lowered relative to competitor hormone
Or can use the ELISA test
Where are the receptors located on the cell
Hydrophillic hormones have their receptors on the cell surface and are transmembrane due to needin the secondary messenger model
Hydrophobic hormones have cytoplasmic receptors as they can pass through the cell membrane
Where are hormones secreted from
The primary endocrine organs
Secondary hormones are secreted for a secondary function
Can be from classical endocrine ductless glands from the epithelia
Can also be from neurones and isolated cells
Also from cells that have an other primary role like muscle and bone
How are hormones controlled
The system used for intsetinal hormones uses secretin and gastrin
There can be hormone paring where have 2 pathways to maintain a range of a substance
Where are insulin and glucagon secreted from
They are both secreted from the pancreas to control the blood glucose levels
Insulin for high blood glucose to lower it and glucagon for low blood pressure to increase it
How is Ca2+ regulated
By the Thryoid and Parathyroid gland that have calcitonin cells and parathryoid cells
If Ca2_ is too high thenn calcitonin from thydroid gland and if too low then secrete parathroyid cells from the parathyroid gland
What happens when too little or too much hormone present
Hyperparathyroidism when too many parathyroid hormones and hypoparathyroidism when too litte paratghyroid hormones
What is the directr feedback control system
How insulin, glucagon anmd parathyroid hormones aee regulated by direct monitoring of factors they control
What is the Neuroendocrine system
Some hormones are organsied in relays that are complex and indirect control. They run through the hypothalamus and anterior pituitary gland in the brain
How does the neuronendocrine system work
This is where tropic hormones act on another endocrine organ that regulate hromone release
Hypothalamus --> Pituitary gland --> Adrenal Gland --> Adrenal, Gonad or thyroid axis
Hypothalamus produce primary tropic factors that then feed onto the anterior pituitary gland that then produce secondary tropic hormones
What are tropic hormones
Have other endocrine glands as their main target such as the anterior pituitary gland
What are non-tropic hormones
These directly stimulate non-endocrine cells and released from pituitary gland which is an extension of the hypothalamus
What are trophic hormones
These can cause a growth effect on the tissue that it stimulates, some can be both tropic and trophic due to make endocrine gland larger
The brain structure for the endocrine system
The hypothalamus is located below the thalmus above the brain stem and link the nervous system to the endocrine system via the pituitary gland
This sits behind the optic chiasma where then the optic nerve from the eye meet the brain
The pituitary gland is at the bottom and is linked by small piece of tissue to the hypothalamus, it is directly linked to the posterior side and is linked to the anterio side by an interconnected blood supply
The hypothalamus secrtete hormones that inhibit or stimulate the pituitary gland
What does rhe hypothalamic control
Body temperature, hunger, thirst and fatigue
This is done by 16 hypothalamic nuclei: Paraventricular nucleus, Supraoptic nucleus and arcuate nucleus
What are the hypothalamic inputs
Nervous stimuli casuing a response: CNS, olfactory stimuli so pheromones, Light - Circadian cycle , Autonomic inputs- Neural inof from heart, digestive and reproductive tracts
Or from:
Plasma borne signals : Endocrine signals, Concentration of glucose and ions, Cytokines and toxins
What are the hypothalamic outputs
Tropic hormones - Releasing hormones by secreted neurons in hypothalamic nuclei and their axons run to local blood ciruclation that then drain to the anterior pituitary gland
Other hypothalamic axons- form the posterior pituitary galdn that secrete neuropeptides to direct systemic cirulation + Non tropic hormones
Nervous signals - Regulate autonomic nervous system
How are tropic hormones released
Action potential in one of the hypothalamic nuclei that then release neuropeptide hormones that enter blood
They then travel quickly at high concentration in hypothothalamic portal vessel to the anterio pituitary gland
They then enter modified capilay bed called sinuses
They can then reach target cells very quickly and at high concentration so then quick release of secondary hormones to then target organs
How are non-tropic hormones released
These bypass the portal vessels due to action potential go direct to posterior pituitaryb gland and then to the body so hormone get to target much quicker
What are the forms of capillay
In the anterior pituiatry gland - There are sinusoid capillaries that have incomplete basement membrane and also intracellualr gaps, to allow tropic hormones to diffsue very quickly through to the anterior pituitary gland
In the Kidneys- These have fenestrations whihc are holes in the wall of endothelium cell for tropic hormones to diffuse quickly to the vascular bed
What are the major hormones released from the hypothalamus
Prolactin inhibibing and releasing hormone
Growth releasing and inhibiting hormone
Throtropin releasing hormone
Corticotropin releasing hormone
Gonadotropin releasing hormone
What anterior pituitary gland do each releasing hormone act on
Thyrotropes - These are targeted by thyrotropin releasing hormone to form thryotropsin and will target the thyroid by the release of thyroxine
Corticotropes - Responed to Corticotropin releasing hormone and form cortricotropin that then target adrenal cortex by the release of corticoids
Gonadotropes - Respond to GnRH anf form gonadatropins these target the testies and ovary by the release of inhin and maturation of germ and follice + limit oestrogen production
Somatatropes - Respond to Somatostatin to form stomatotropin and target the liver cells by protein production
Lactotropes - Respond to Prolactin and form lactotropin and target mammary glands by growth of gland and lactation
How is this controlled in the hypothalamus to where a hormone is released from endocrine organ
There is a long feedback loop to the hypothalamus as well as a short feedback loop so extra regulation
Can lead to spikes in hormone concentration at times due to differing feedback loops at different times
This can cause disease sue to tumours loose responsiveness to some hormones
What hormones are produced in the posterior pituitary gland
Oxtytocin and ADH are both non tropic hormones
How is ADH regulated and secreted
Secretion is induced by central osmoreceptors when there is increase in osmolarity
Reduced plasma volume triger baroreceptors in aortic arch and carotids sinus that signal via nagal nerves to the CNS
Angtiotensisn 2 triggers ADH to lower blood pressure by inserting aquaporins in the collecting duct
What does ADH do
Bind to G coupled receptoes in blood vessel smooth muscles and Kidney receptors
In blood vessels - Cause increase in blood pressure as increas vascoconstriction
In Kidney- Increase water uptake by acting on collecting duct and distal tubule, it will insert aquaporins to collecting duct, stimulate NaCl uptake and more water retention
What does Oxytocin do - paraventricular nucleus
Regulation- Sensory nerve inputs from stretching of the cervix or suckling of the nipple
Action - Contraction of myoepithelial cells and smooth muscles in mammary gland so milk released
Contraction of smooth muscle in uterus during birth
Effect bonding of male and females
What is the hypothalamic pituitary adrenal gland
A hormonal axis that respond to long term stress rather than fight or flight responses as well as ot secondarily maintin the body sodium balance
How does the Hypothalamic Pituitart adrenal axis work
The hypothalamas will release the hormone corticoltropin releasing hormone that will then bind to cortiocoltropin cell in the anterior pituitary gland
This then cause a G protein signal so that the adrenal corticol trophic hormone - ACTH is released from the anterior pituitary gland and this will go to the adrenal cortex
Thsi then cause the adrenal glands to release aldosterone cortisol that then effect NaCl and water reabsorption in the Kidney
What is the structure of the adrenal glands
They are not part of the Kindeys
Made up of 3 areas:
Zona Glomerulose - releases aldosterone
Zona Fasticula - Releasing cortisol and androgens
Zona Reticularis - Releasing cortisol and androgens
The centre part is called the medulla and is classic nerve cells but without axons and produce adrenaline and noradrenaline
Outside is called the cortex and made of epithelial cells that proeduce the steroid hormones and are the 3 layers
What are steroid hormones
These are all lipid soluble so cant be stored in the cell so made and then secreted:
Oestrogen, Progesterone and Testosterone are all sex hormones
Glucocorticoids
Mineralcorticoids
Vitamin D
What are the key features of the full adrenal axis pathway
Cholesterol desomolase will modify side chains of cholesterol and release cortisol and this will start the path so is the inducer
Enzyme 17C hydrolase will change the pathway so that cortisol is produced and can also lead to production of androstendione as a side reaction
The 3 main products = Corticosterone, Cortisol and androstendione
This pathway is regulated bt ACTH and form in the fasicular and retiular level of the adrenal glands
How does the adrenl pathway differ in the glomerulose layer
Have the same inducer,but when there is angiotensin 2 present it mean that aldosterone synthase enzyme is active so allow coritcosteroid to be converted to aldosterone
The aldostrone ism much more active and greater enhancer effect from less produced
If there is no angiotensin 2 then corticosteroid is produced
What is the stimuli for corticol release
Circadrian rythm and stress levels lead to production:
Lead to hypothalamic release of corticotropin releasing hormone that bind to corticotropin cells in anterio pituitary gland so then ACTH released that goes to the adrenal gland and causes cortisol release
How do adernocorticoids function
They are lipid so can diffuse over cell membrane so have cytoplasmic receptors that they bind to and cause a conformational change in the receptor so it can go to nucleus and target certain genes
What are the 3 functional domains of a steroid hormone receptors
Lignad binding to the steroid - Contain nuclear translocation signal along with chaperone that stop signa working without the hormone present
DNA binding domain - This intercat with the target genes on the DNA
Ligand dependent transcription domain - Make the complex at nuclear level and induce gene transcription by intercat with RNA polymerase
What are hormone receptor binding elements
Short cis acting sequences located within promoters or enhancers of the target genes
How is there steroid specificity
Cell has to express the receptor as well as the coactivtor at the same time for hormone to bind to it
What do glucocorticoids drive
Catabolism which are metabolic pathway that break down molecules to release energy
Cause protein break down in many tissue for amino acid release
Lipids are broken down for mobilisation of fatty acids
Carbohydrates -save glucose and rakise blood glucose and increase glycogen formation in the liver
How are Glucocorticoids anti-inflammatory
Due to allow higher blood glucose level without increasing muscle activity so less likely to tire so may be used for doping
But too much may cause tumours in the adrenal cortex or secondary ones in the hypothalamus and anterior pituitary gland
What are the mineralcorticoids = Aldosterone
These are produced in the zona glomerulosa and ACTH is needed to start the pathway but it is regulated by angiotensisn 2 levels
What does aldosterone do
Can lead to lower Na+ excretion as more is reabsorbed in the collecting duct and more water also reabsorbed so extracellular volume increases
How is aldosterone regulated
Blood enter the zona glomerulosa and around the blood vessels afre muscle cells called juxtaglomerula cells
As blood pressure decreases muscles cell get stretched but when they are not stretched they excite and release Renin
Renin cleave angiotensinogen to angiotensin 1
Angiotensin converting enzyme then convert angiotensin 1 to angiotensin 2 that regulate aldosterone
What is the stimulation of the Renin/aldosterone system
Low blood pressure detected by the Juxta glomerula cells
Low Na+ and high L+ detected in gthe fluid of distal convulated tubule due to filtration and so Macula Densa cell activate JG cells
JG cells then release the Renin
It can be inhabited by high blood pressure monitored by atrial muscles in the heart that produce ANHF to block renin
What is the aldosterone function
Maintain ion balance and ADH mainlly for water retention
Will release mineralcorticoids
Increase apical membrane Na+ and K+ channels and start basal pumos for them
Involved in metabolism
Overall increaser Water and Na+ and lower K+ and H+
What is the role of ACTH and CRH
This is corticotropin releasing hormone from the hypothalamus and then bind to anterior pituitary gland to cause secretion of adronocorticotropic hormine
What is addisons disease
When have reduced mineralcorticoids means low blood pressure, loss of Na into urine and greater K+ in extracell fluids
This can lead to muscle weakness and if untreated lead to death by cardiac systole
What are the genetic factors + Environmental factors that control metabolism from the hyothalamus and Pituitary gland
Genetic - Growth hormone, Thryoid Hormone, Glucocorticoids
Environmental - Food our level of hunger is controlled by Grehlin, Adipose tissue is reduced to leptin to make us feel less hungry and our Blood sugar controlled by glucagon and insulin
What is the normal blood glucose level and what happen if it drops
The normal range is around 70-90mg per 100ml
If there is a slight drop then lead to glucagon and epinephrine released and may get tired and short tempered
If drop so low then lead to coma and then death eventually
What does the liver do to control blood glucose levels
It is a store of sugar that can be given out to the rest of the body. It store glycogen and release as glucose when blood glucose too low and can alos carry out gluconeogenesis and make Ketone bodies that carry sugar round the body
What does insulin do
It will increase glucose oxidation and glycogen synthesis
Increase in protein synthesis
This is done to lower the blood glucose
What does glucagon do
Increase in glyucogenolysis, gluconeogenesis and more ketone bodies are formed
This is too raise blood glucose levels
How is glucose broken down
Glucose is primed by GlucoKinase to Glucose-6-Phosphate that is then changed to fructose by PhosphofructoKinase
Frcutose go to glyceraldehye and then to Pyruvate
Pyruvate is then turned to acetyl CoA that is then oxidised to release 2 CO2 molecules
What happnes in the TCA cycle when you are starving
There is lower blood glucose so liver convert fatty acid to ketone bodies to move sugar around the body
2 acetly CoA are joined together to make acetoacly CoA that can be turned to B hydroxyl methylglutaryl CoA
This then turned to acetoacetate that then fed to other tissues and turned back to acetyl CoA to feed the TCA cycle
What happens is blood glucose is too high -effects
Glucose is lost in the urine in the renal filtrate so not all us reabsorbed in the Kindey
If this is long term then change in metabolic activity due to greater glycation and more cholesterol laid down so heart attack ect
What is Insulin
It will induce the use of glucose for the formation of glycogen
Induce uptake of amino acids for protein formation and stop protein breakdown
It is secreted from the B cells in the islets of Langerhanns in the Pancreas
How is insulin secreted
Glucose levels monitored by B cells
If there is high blood glucose then ATP is formed so that will close ATP gated K+ channels so then depolarisation and inuslin exocytosis
This is driven by increase: blood glucose, blood fatty acids, blood amino acid
It can be limited by: lowering blood glucose, adrenergic activity so more stress
How does Insulin signal to cells
It is a class 2 receptor so is on the cell surface as 1 unit
There is an alpah unit for the insulin binding domain
Beta unit in plasma membrane and intracellular for domain of tryosine Kinase binding held by disulphide bridges
When insulin bind to A causes conformational change in B units
Induce docking of signalling protein IRS 1
What are the effects of insulin signalling
Rapid transfusion of intracellular vacuoles to the cell surface that carry the insulin
Cause membrane to become more glucose and amino acid permeable
Activation of enzyme for glycogen production
How does Glycogen production take place
Insulin bind to receptor to then producve IRS 1 protein, that can then bind to P1-3K that changes to PKB
PKB then activate GSK3 to activate glycogen synthase
Then lead to greater glycogen synthesis and less glycogen hydrolysis
How is glucagon is released
Released from alpha cells in the pancreas when lower blood glucose
Lower ATP when low glucose levels so K+ ATP gated ion channels close but Na still enter so cause depolarisation
Voltage gated ion channels opne in alpha cell and vesicles with glucagon fuse with membrane and release glucagon out of them
What causes glucagon to be released
Low blood glucose levels
Excersie will increase output
High amino acid levels
How does Glucagon work
It bind to G protein receptor on the liver so activate adrenaline/nor to actibvate adenyl cyclase
This then convert ATP to cAMP
cAMP then activate protein Kinase A that then activate glycogen phopshorylase so convert glycogen to glucose
What will glycoegn cause
Cause Glycogenolysis so break down glycogen to glucose
Cause gluconeogenesis and greater insulin uptake
What are the 2 forms of diabetes
Insipedus - uirine with no taste so lack ADH and is autoimmune disease
Mellitus so uri9ne is sweet tasting so too much blood glucose due to insulin failure
What are the 2 forms of mellitus diabetes
Type 1 = Failure to produce insulin due to damaged Beta cells
type 2 = Liver cells no long respond to insulin due to environmental factors
How are reprodcutive hormones released
Via the hypothalamus that relase gonadotropin releasing hormone that bind to the anterior pituitary gland
Causes the release of FSH or LH that bind to the gonads
From the gonads can either produce oestrogen, progesterone or testosterone
What is the sexual hormonal pathway in males
GnRH released from hypothalamus and bind to gonadotropin in anterior pituitary that then release either FSH or LH
If FSH released then steroli cells made and if LH produced the leydig cells are made
Leydig cells make testosterone that then go to steroli cell to be turned to dihydortestosterone that is a stronger androgen
What is the strructure of the testis
800 Metre of seminifereous tubule that are lined with stem cells making spermatazoa that is released vua rete testis to epididymis wjhere it then mature so it can be fertile
What is spermeogenesis
The stage of differentiation after 2nd round of meiosis, so get haploid DNA pushed back to mitochdonria to make the head of sperm the flagella tail form for sperm to swim
This happen in the steroli cells
What takes place at male puberty
Sperm cells are inactive beforehand and not dividing bit at puberty get large testosterone burst to drive division
Type A spermatogoani divide by mitosis and keep happening if the stem cell are parrallel to testis capsule
How is testosterone made in the Leydig cells
These have LH receptors that when LH bind lead to cholesterol desmolase start steroid pathway
Progesterone is prodiced and turned to androstendione that is then turned to testosterone
LH stimulation is limiting step
Testosterone then immediatly moved to the steroli cells
What takes place in the steroli cells
FSH can bind that lead to production of androgen receptor expression
Testosterone from leydig cells then bind to receptor and is converted to dihydrotestostrone that is a stronger androgen that then stimulate spermatogenesis
What does Testosterone do
There are non-reprodutive so will up muscle mass and bone density before birth
Maturation of sex organs
Droves mitosis of spermatogonia stem cells
What are the stages of female hormonal action
Follicular and Luteal phase in the ovary
Proliferative and secretory phase in the Uterus
What is the hormonal pathway in the proliferative stage
GnRH from hypothalamus bind to anterior pituitary gland and bind to anterior pituitary gland where FSH or LH released
LH released then bind to thecal cells that release androgens to granulose cells and if FSH released they directly bind to granulose cells
The granulose cells release 17B estradiol
What is Ovarian follicle growth
150,000 follicle at puberty with singl eoocyte per one that can convert testosterone so non is present
Granuolose cell surrounded by the oocyte and the thecal cell surround the granulosa cell
1 mature follice with ovulate per month and produce an ovem that could be fertilsied and 19/20 will degenerate
How is follicle growth regulated
Hormone is oestrogne that made from the aromatase of testosterone and androstendioen produced in the thecal cells
Oestrogen production take place in granulosa cells
What does oestrogen do
Stimulate epithelial cell growth in uterus
Stimulate growth of granulosa cells in follicles
Stimulateb granulosa cells to have more FSH recepto so more oestrogen production so + feedback loop
How is ovulation caused
Rise in LH at end of follicular phase so high level of 17B estradiol so dominat follicle formed
Domiant follicle ruptures to release oocyte to reproductive tract
What happens after ovulation
In the secretory and luteal stages of hormonal cycle and there is the formatipn of the corpus luteum whihs is a post ovulatory follicle
How is the Corpus Luteum formed
17B estradiol stimulate granulosa cell to make LH receptors so these cells are now main steroid forming cell
The is leutenisation of graafian follicle to corpus luteum
What does large volume of progesterone in the granulosa cell do
Progesterone levels rise after ovulation and so will lower FSH production so stop follicle forming
Reduve LH production so block 2nd ovulation so dont have 2 cycle at same time
Change uterus for implantation and ready for pregnancy
What happens in the uterus of proliferative and secretory phase
Ooctye is released to fallopian tube where fertilisation occurs and 3-4 days for embyro to pass to the tube
What is the structure of the uterus
Myometrium is a muscle layer that get thicker during pregnancy
Endometrium is the inner stromal and lining of epithelial cells
Epithelia is site of embryo implantation and cerix is neck of thr uterus
Cervix is closed by the musuc plug excpet for 3 time sdring ovulation, period bleeding and birth
What is the role of progesterone and 17B estradiol in uterine growth and implantation
in proliferative stage 17B estradiol stiumulate stromal and epithelical cells ton grow so gland formation
After ovulation get more progesterone that drive secretion of protein and glycoprotein from gland to nurtue embryo
What are the 3 layers of the uterus
Cytrophoblast and Synctyiotrophoblast and Hyopblast
Pregnancy is detected by presence hCG produced from Synctyiotrophoblast and that tell mother to not start another cycle
What does cGH do
Signal to keep the corpus luteum and use LH receptor on the Corupus luteum cell
Maintaion corpus luteum by binding toi the LH receptor ans act on it
Why does the Corpus luteum need embryo survival
LH lead to loss of corpus luteum after ovulation, in the absenvce of embyro there will be no LH or FSH produced so Corpus luteum die that lead to periods
How does whole cycle start again if no pregnancy
Lutoelysis death of corpus luteum caysed by progesterone and no cGH to maintain it
Loss of corpus luteum lead to FSH rise again and new cycle
What does progesterone do during pregnancy
Block follice development and ovulation
Barier at the cervix as they cervical plug so no bacteria enter uterus
Induce uterine endometrium to make nutrient rich food for uterus
What is Partruition
Timing from the start of labour from the first day of pregnancy usually about 9 months.
Controlled by changing ratio of hormones of corticotropin releasing hormone to then at the end release cortsiol
How is pregnancy started
Placenta is an endocrine organ, and the fetal adrenal glands grow so more cortisol produced
Cortisol stimulate conversion of progesterone to 17B estradiol and so trigger partruition
What is the partruiton start point
Placenta CRH production under + feedback loop so more CRH bind to anterior pituitary gland so more cortisol production
Corstiol bind to glucocorticoids so then more CRH made
CRH will increase expression of oxytocin in myometrium of uterus
What does oxytocin do
Induce endometrial myometrial contraction to push baby further to cervix till birth or mother death