endocrine system and challenges (ghrelin, ADH, brain, body mass)

Question 1

Which of the following hormone(s) causes a decrease in fat mass?  
A Insulin
B Oestrogen
C Leptin	
D Adiponectin	
E Growth hormone

Answer 1

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

Question 2

how does progesterone affect body mass?

Answer 2

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

Question 3

how does testroone affect body mass?

Answer 3

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

Question 4

how does ghrelin affect body mass

Answer 4

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

Question 5

how does cushing syndrome affect fat mass?

Answer 5

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

Question 6

how does glucagon affect fat mass

Answer 6

decreases fat mass in mesenteric and retroperitoneal fat depots
increases processes of gluconeogenesis and glygogenolysis and inhibits glycolysis
can increase liplysis

Question 7

how does insulin affect fat mass?

Answer 7

promotes glucose uptake by glut4 receptors

increase fat mass and promotes lipogenesis and glycogen synthesis

Question 8

describe the different fat depots

Answer 8

subcutaneous - superficial or deep
mesentaric - within the abdominal cavity
retroperitoneal - small depot
epididymal fat and inguinal fat - groin/geneital area

Question 9

where can brown fat be found? what do?

Answer 9

brown fat found in intrascapluar region, around neck
perirenal and pericardial
around blood vessels too

involved in diet induced + non-shivering thermogenesi

Question 10

how can hormones signal?

Answer 10

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

Question 11

what is a hormone?

Answer 11

A chemical signalling molecule secreted from an endocrine gland which acts on a target organ to exert and effect``

Question 12

how is hormone different from a neurotransmitter

Answer 12

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

Question 13

can you name the 5 secretory cells of the anterior pituitary gland?

Answer 13

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

Question 14

describe how the post and ant pitutiary devlelop in embryo

Answer 14

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

Question 15

what is another name given to the posterior pituitary
A pars intermedia
B pars nervosa
C adenohypophysis
C median eminance
E neurohypophysis

Answer 15

OPTION B AND E

posterior pituitary relates to the nervous system

Question 16

where are the cell bodies of the neurosecretory cells located that project into the Posterior Pit and the Anterior Pit?

Answer 16

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!

Question 17

how is oxytocin release stimulated?

Answer 17

stimulated upon stretch receptors of uterus and will be released from anterior pitutary
to help uterine contractions and milk ejection in response to suckling

Question 18

how is ADH release stimulated (FROM THE PVN)

Answer 18

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

Question 19

why are levels of TRH hard to detect?

Answer 19

only a small peptide hormone of 3 aa so has a short half life

Question 20

describe a pathology associated with too little oxytocin

Answer 20

could result in failure to suckle

Question 21

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

Answer 21

OPTION B

too little ADH means that we don’t retain water, frequent diuresis and polydipsia/thirsty

Question 22

how can one detect where mRNA is expressed?
A methylation assay
B northern blot
C insitu hybridisation
D western blot

Answer 22

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

Question 23

descirbe sturcutre of ADH gene

Answer 23

3 exons and 2 introns

encodes the signal peptide, adh pro hormone, neurophysin and glycopeptise

Question 24

describe how adh gets processed

Answer 24

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

Question 25

why do magnocellular neurons of PVN respond to osmotic stress but not the parvocellular neurons?

Answer 25

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

Question 26

describe the ADH receptor, where is it expressed

Answer 26

(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

Question 27

which aquaporin is regulated by ADH?
A AQP3
B AQP2
C AQP4
D AQP1

Answer 27

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

Question 28

describe the importance of ADH/V2 RECEPTOR signal cascade

Answer 28

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

Question 29

where are aquaporin2 mielcules usually founf

/

Answer 29

just below the the luminal surface

seem to maintained their by interacting with microtubules, tubular motor proteins, actin filaments and docking proteins

Question 30

what are the roles of AQP3 and AQP4

Answer 30

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

Question 31

what are adipogenic markers

Answer 31

C/EBP and PPAR gamma are markers of terminal adipocyte differentiation

increased by prolactin, insulin, glucocorticoid, ghrelin
decreased by GH, testorone, oestrogen

Question 32

how is lipids in diet take up by cells? (exogenous pathway)

Which lipoprotein

Answer 32

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

Question 33

what does lipgenesis involve

Answer 33

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

Question 34

where can Brown adipose tissue be found? what does it do? why is is called brown?

Answer 34

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

Question 35

decribe the enzymes involved in lipgeneisis and lipolysis

Answer 35

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

Question 36

how is oxytocin regulated? what stimulates its release

Answer 36

released upon cervical stretch receptors of uterus and mammary glands to help uterine contraction (postive feedback)
and lactation/milk ejection upon suckling of nipple

Question 37

why does it take so long for uterine contractions to begin, despite oxytocin mRNA increasing throughout pregnancy

Answer 37

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

Question 38

how are glial fibres regulated?

Answer 38

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!!