endocrine system and challenges (ghrelin, ADH, brain, body mass) Flashcards
Which of the following hormone(s) causes a decrease in fat mass? A Insulin B Oestrogen C Leptin D Adiponectin E Growth hormone
GROWTH HORMONE + LEPTIN
GH - increase lipolysis and increases protein synthesis so we get increased muscle mass
Letpin is an adipokine released from fat cells and is a SATIETY SIGNAL, will pressures appetite by exciting POMC/CART neurons
inuslin, oestrogen and adiponectin will increase lipid storage
how does progesterone affect body mass?
increases the fat mass pad in the groin/inguinal region and esp. the hip! in the females
can induce expression of lipogenic genes like FA synthase and so increase lipogenesis
how does testroone affect body mass?
can reduce adipogenesis (evidence is hypogonadism correlated woth elevated fat mass)
so as testosterone dosage goes up, fat cell number decreases as there is reduced PPAR gamma and C/EPB alpha
how does ghrelin affect body mass
can stimulate adipogenesis/lipoplysis in the bone marrow and intraabdominal fat
so only specific fat depots are increased, not all
HUNGER SIGNAL released from stomach in response go undernutrition
how does cushing syndrome affect fat mass?
increase in glucocorticoids (cortisol) so there will be an increase in fat mass
promotion of adipogenisis and lipogenesis in bone marrow and intraabodominal fat tissue
how does glucagon affect fat mass
decreases fat mass in mesenteric and retroperitoneal fat depots
increases processes of gluconeogenesis and glygogenolysis and inhibits glycolysis
can increase liplysis
how does insulin affect fat mass?
promotes glucose uptake by glut4 receptors
increase fat mass and promotes lipogenesis and glycogen synthesis
describe the different fat depots
subcutaneous - superficial or deep
mesentaric - within the abdominal cavity
retroperitoneal - small depot
epididymal fat and inguinal fat - groin/geneital area
where can brown fat be found? what do?
brown fat found in intrascapluar region, around neck
perirenal and pericardial
around blood vessels too
involved in diet induced + non-shivering thermogenesi
how can hormones signal?
they can bind to nucleic or cytosolic receptors to alter gene transcription e.g oestrogen and cortisol
they can act as secondary messengers and bind to GPCR or cytokine/JAK/STAT receptors on cell surface e.g. ADH and growth hormone
what is a hormone?
A chemical signalling molecule secreted from an endocrine gland which acts on a target organ to exert and effect``
how is hormone different from a neurotransmitter
hormone has to transported in the blood to the target tissue and can have longest lasting actions (slower signal transmission)
neurotransmitter travel along axon terminals and synaptic clefts to communicate between never cells,
hormones produced by endocrine system, neurotransmitter produced by nervous system
only stimulate postsynaptic neurons
can you name the 5 secretory cells of the anterior pituitary gland?
thyrotroph produce TSH – 5%
gonadotroph produce LH/ FSH – 10%
cortIcotroph produce ACTH –15-20%
somatotroph produce GH – 50%
lactotroph produce prolactin – 10-25%
i guess somatomammotrophs
describe how the post and ant pitutiary devlelop in embryo
ant: upgrowth of pharnyx // non neuronal tissue. forms Rathkes pouch after 4-5 weeks
post: down-growth of 3rd ventricle, neuronal tissue
Problems can lead to kallman syndrome - hypogobadism and lack of smell
what is another name given to the posterior pituitary A pars intermedia B pars nervosa C adenohypophysis C median eminance E neurohypophysis
OPTION B AND E
posterior pituitary relates to the nervous system
where are the cell bodies of the neurosecretory cells located that project into the Posterior Pit and the Anterior Pit?
hormones of the posterior pituitary are released from neurosecretory cells with cell bodies located in supraoptic nucleus (SON) and paraventricular nucleus (PVN)
hormones of the anterior pituitary are released from neurosecretory cells with cell bodies located in -
SON, PVN, arcuate and median preoptic nucleus as well!
how is oxytocin release stimulated?
stimulated upon stretch receptors of uterus and will be released from anterior pitutary
to help uterine contractions and milk ejection in response to suckling
how is ADH release stimulated (FROM THE PVN)
in response to low blood volume/pressure and high plasma osmolarity and magnocellular neurons of the PVN project to the posterior pit to release ADH which
will increase expression of aquaporin2 on CD basal membrane and increase water absorption
parvocellular neurons of the PVN will project to the anterior pituitary and release ADH which stimulate corticotrophs to secrete ACTH
why are levels of TRH hard to detect?
only a small peptide hormone of 3 aa so has a short half life
describe a pathology associated with too little oxytocin
could result in failure to suckle
what pathology of low ADH is an example of?
A laron syndome
B diabetes insipidus
C cushings sydrome
D Syndrome of inappropriate antidiuretic hormone secretion
OPTION B
too little ADH means that we don’t retain water, frequent diuresis and polydipsia/thirsty
how can one detect where mRNA is expressed? A methylation assay B northern blot C insitu hybridisation D western blot
use in situ hybridisation which probes mRNA to find its location
probe is labelled fluorescenlly or radio-labelled
a northern blot can be used to see if mRNA is present but not the actual location (say on a brain tissue section
descirbe sturcutre of ADH gene
3 exons and 2 introns
encodes the signal peptide, adh pro hormone, neurophysin and glycopeptise
describe how adh gets processed
translated and signal peptide directs the protein to the golgi network where it can be packaged into large dense core vesicle and secreted from posterior pituitary
as this is happening, the protein gets cleaved by proteases into its 3 components an`d neurophysin can form a tetrameter and act as chaperone for ADH
why do magnocellular neurons of PVN respond to osmotic stress but not the parvocellular neurons?
because of astrocytes which are fibres that run through neurons and assoicate with aquaporins4
upon osmotic stres they draw water out of the magnocellular cwlls but not the parvocellular cells and the cells shrink which stimulates ADH release
astrocytes are found in the PVN, SON and OVLT
describe the ADH receptor, where is it expressed
(specifically the v2 receptor)
its a GPCR so 7 transmembrane domains
its expressed on basal membrane of CD of kidney
upon binding to ADH will increase cAMP production allowing AQP2 to fuse on the luminal surface of CD
which aquaporin is regulated by ADH? A AQP3 B AQP2 C AQP4 D AQP1
OPTION B - NUMBER 2
AQP4 can interact with astrocytes to remove water under osmotic stress and initiates the magnocellular neurons to release ADH
ADH can then travel to collecting duct to increase the translocation of AQP2 vesicles fuse with luminal surface to increase water retention
describe the importance of ADH/V2 RECEPTOR signal cascade
increse in cAMP will activate PKA
PKA phosphorylates AQP2 which is necessary for function of AQP2 as a water channel
> makes it more effective, increases permeability of cell membrane quite considerably
where are aquaporin2 mielcules usually founf
/
just below the the luminal surface
seem to maintained their by interacting with microtubules, tubular motor proteins, actin filaments and docking proteins
what are the roles of AQP3 and AQP4
not under control of ADH
but usually expressed on the basal surface of CD and this allows the water to be reabsorped back into circulation
> if no AQP3+4 then the cell will swell and bursssst
what are adipogenic markers
C/EBP and PPAR gamma are markers of terminal adipocyte differentiation
increased by prolactin, insulin, glucocorticoid, ghrelin
decreased by GH, testorone, oestrogen
how is lipids in diet take up by cells? (exogenous pathway)
Which lipoprotein
this is the exogenous pathway of cholestrol uptake
food/chyme mixes with bile salts to emulsify them and react with pancreatic lipase
FFA+ glycerol taken up by enterocytes of the gut
re-esterified to TAG and cholesterol into the lipoprotein CHYLOMICRON which has ApopB48 recognized by liver cells
travels in circulation, degraded by LPLipase to hydrolyse TAG to FFA andglycerol and taken up by tissue to be used as energy or stored
what does lipgenesis involve
lipogenesis is the creation of new lipid. catalyzed by fatty acid synthase
substrate needs to be uptaken into adipocyte cell in order to do this (upregulate GLUT4, CD36, lipoproteinlipase expression)
lipolysis is the breakdown of lipids which can be done by hormone sensitive lipase
where can Brown adipose tissue be found? what does it do? why is is called brown?
between shoulderblades, interscapula peri-renal and peri-cardinal BROWN as its full of mitochondria >> this is activated in thermogenesis // nonshivering thermogenesis to regulate body temperature > very profound in newborns
decribe the enzymes involved in lipgeneisis and lipolysis
so lipoproteins release the FFA and glycerol. The tissues can use fatty acid synthase to re-esterify them and store as fat in adipose tissue = genesis
so for cells to use fat as energy, hormone sensitive lipase can respond to adrenaline to hydrolyse lipids to FFA and glycerol which can the be used in FA metabolism to generate ATP but also ketone bodies if there is excess = lipolysis
how is oxytocin regulated? what stimulates its release
released upon cervical stretch receptors of uterus and mammary glands to help uterine contraction (postive feedback)
and lactation/milk ejection upon suckling of nipple
why does it take so long for uterine contractions to begin, despite oxytocin mRNA increasing throughout pregnancy
because of NEURONAL QUIESCENCE
opiods released from pituitary can actually supress neuronal activity in the SON and prevent oxytocin being released into circulation
if you treat with opioid antagonist then the activity will increase and oxytocin will be released into environment
how are glial fibres regulated?
glial fibres usually keep neuronal cells apart
> suckling and local release of oxytocin in hypothalamus will result in glial fibre withdrawal
so and emergence of SHARED SYNAPSES so neuronal cells work together as a functional synthium = synchrony of AP
== lactation!!
