Neuropeptides and Hormones Flashcards
What are neuropeptides?
(2 marks)
- Small proteins produced by neurons
- Act on GCPRs and responsible for slow onset, long lasting modulation of synaptic transmission
What are the two families of neuropeptides?
(2 marks)
- Small molecule NT: GABA, glutamate etc,
- Peptide NT: range of brain and gut peptides (in particular hypothalamus)
Name some of the mammalian neuropeptides:
(5 marks)
- Opioids
- Pituitary peptides
- Hypothalamus releasing peptide
- Peptide neurotransmitter
- Brain-gut peptides
How is proopiomelanocortin (POMC) produced in the secretory granule?
(9 marks)
- Made in humans on chromosme 2, coding in exons 2 and 3 give rise to production of pre-POMC
- Signal peptide: instructs machinery of cell as to where to send product - to Golgi cortex & comes out secretory granule (only in POMC)
- Signal peptide cleaved off and POMC enters granule whcih is then spliced by PC1 (pro-convertase enzymes)
- Formation of PC1 forms ACTH and ß LPH
- ^^ subject to PC2 to get γMSH and αMSH
- Cleave off 5’ part and PC1 cleaves another structure forming ACTH and ßLPH
- ßLPH cleaved by PC1 forming: γLPH and ßMSH & ßendoprhin
- ACTH cleaved by PC2 forming αMSH and CLIP peptide
In cows, why does the relative expression of Kiss/Dyn change?
(2 marks)
- Due to reporoductive cycle
- BUT can be co-expressed in neurons and secretoru granules that contain both of them
What is the difference in function between G proteins GHRH and SRIF?
(2 marks)
-
GHRH:
- Signals through Gαs which activates adenylate cyclase
-
SRIF:
- Binds to SSTR1-5 receptor and activates Gαi which inactivates adenylate cyclase
What loop of the G-protein receptor interacts with the G-protein?
(2 marks)
- 3rd intracellular loop
- Binding to receptor causes α-subunit to dissociate and activate substrate molecule
What does the G protein OXY do?
(4 marks)
- Binds to OTR
- Causes dissociation of Gαq
- Activates PLC and produces IP3 and DAG
- IP3 increases intracellular Ca2+
- DAG increases extracellular Ca2+
What is another word for the anterior pituitary?
Adenohypophysis (pars distalis)
What is another word for posterior pituitary?
Neurohypophysis (pars nervosa)
What is another name for intermediate lobe?
Pars intermedia
Outline the basis of posterior pituitary circulation.
(6 marks)
- Pituitary sits in sella turcica
- PP receive blood from inferior posterior artery by capillary plexus of infundibular process
- Blood taken away from posterior hypophyseal veins
- Pituitary gland contains neuron terminals with cell bodies in paraventricular nucleus and supraoptic nucleus
- Neurons project down through pituitary stalk and terminate in posterior pit
- So pituitary stalk acts as neuronal tract
Outline the blood supply for the anterior pituitary.
(6 marks)
- Blood supply from superior hypophyseal artery
- Enters primary plexus of hypophyseal portal system
- Blood leaves via hypophosal portal veins (blood leaves secondary plexus by anterior hypophosal veins)
- Which goes down pit stalk and into secondary plexus of hypophyseal portal system
- Neuropeptides made in hypothalamus
- Neurons release into primary plexus, go down pitutitary stalk by hypophyseal veins and activate/ inhibit cells in AP
Describe what the structures and their location in the picture.
- Rostral end of hypothalamus indicated by anterior commissure and potic chiasm
- Preoptic area on front wall of 3rd ventricle
- Caudally find nuclei on either side of 3rd ventricle
- Supraoptic nucleus (either end of optic chiasm)
- Periventricular nuclei up against 3rd vwntricle wall, laterally and dorsally from that is paraventricular nucleus
- Further back is arcuate nucleus has neurons projecting to median emminence and primary plexus
- Completely caudally is posterior nuclei and mammillary body
What hormones are present in the posterior pituitary?
(2 marks)
- Vasporession
- Oxytocin
What is the function of Vasopressin?
(2 marks)
- Controls kidney at higher concentrations and can cause vasoconstriction
- Associated with diabetes insipidus-receptor as isn’t responding so get lots of dilute urine
What controls the levels of secretion of vasopressin?
Plasma osmality and blood volume
What is the function of oxytocin?
(5 marks)
- Milk ejectoin
- Uterine contraction
- Suckling:
- information comes from spinal reflex arc to paraventricular nucleus. Stimulus is cholinergic and transmitted to nerve endings in PP
- Causes Ca2+ uptake - depolarisation and exocytosis of oxytocin into circulation
What are the different anterior-pituitary axes?
(5 marks)
- HP-thyroid
- HP-adrenal
- HP-Growth hormone
- HP-prolactin
- HP-Gonodal
What is produced in the HP-thyroid axis and what does it do?
(5 marks)
- Neurons at top produce TRH (thyrotropin releasing hormone)
- Found in parvocellular portion of paraventricular nucleus
- TRH - 3 AA peptides and therefore has short half life
- TRH activates thyrotrophs which then release TSH - protein hormone
- Thyrotophs under single positive regulation
What is produced in the HP-adrenal axis and what does it do?
(5 marks)
- Corticotrophs (placental hormones)
- Controlled by positive regulation by 2 NP one being vasopressin which influences ACTH secretion
- Corticotrophs found in anteriore pituitary and stimulate secretion of ß endorphins from anterior pituitary and other POMC derivatives
- Corticotrophs give neuronal input to neurons from limbic system and brain stem areas for autonomic controls
- CRH - important in stress response
What is produced in the HP-growth hormone axis?
(3 marks)
- Somatotrophs which are under negative and positive regulation
- Positive regulation by GHRH - produced by neurons who’s cell bodies are in arcuate nucleus
- Negative regulation by somatostatin (SRIF) - cell bodies of neurons that make this found in perventricular nucleus
What is produced in the HP-prolactin axis and what factors affect its functionand expression?
(6 marks)
- Lactotrophs which are under negative regulation
- Secreted by neurons in dorsomedial area of arcuate nucleus and inferior ventromedial nucleus
- Secretion is inhibted by DA neurons which inhibits the release of _prolactin from lactotrophs_
- Damage to pit stalk prevetns DA coming down stalk and get Loss of secretion of all pit hormones bar prolactin which increases
- Less intracellular Ca2+ causes reduced exocytosis of secretory resideus containing prolactin
- Inhibition of adenyl cyclase further reduces Ca2+ (in cell) and causes decreased prolactin gene expression
What is produced in the HP-gonodal axis?
(3 marks)
- Gonadotrophs - under positive regulation by GnRH neurons
- cell bodies in casculosom of lamina terminalis
- Neurons project down to medium emminence and elicit secretion of LH and FSH to control reproductive
How is GnRH stored and secreted?
(3 marks)
- Primary signalling pathway is through activation of PLC which releases IP3 and DAG and activation of PKC
- Signals transmitted through JNK pathway to activate transcription of gene for ß-subunit of either LH or FSH
- Increase in cAMP and intracellular Ca2+ from activation of voltage sensitive Ca2+ channels
What is the basic stages of GnRH migration during neurogenesis?
(5 marks)
- Neurogenesis
- Initiation
- Divergence
- Progression
- Arrest
What is the developmental process of the GnRH system.
(9 marks)
- Neurogenesis controlled by FGFs - GnRH neurons orginiate in late olfactory placode
- Movement of GnRH neurons to prefrontal cortex, and adhesion to axons in vomero nasal organ
- GnRH converge away from dorsal VMO across cribiform plate and into main part of brain. Controlled by Sema3A & Nrp1/2
- @ same time as divergence, have proliferation of gonadotrophs in anterior pituitary controlled by GATA2 (TF)
- Neurons progress down neuronal guides & controlled by some other proteins Acl, SDF-1, Nhlh2 and progressing down towards AV3v
- Neurons interact with Kisspeptin (kp) neurons at specific region then terminate their migration and kp no longer expressed
- GnRH neurons porject down to median emminence @ same time kp neurons and GnRH neurons begin to form their synaptic connections with other neurons
- Leptin controls entry to pubity: need gd fat storage, activates neurons to activate kp neurons which activates GnRH neurons and BAM pubity
What happens in the hypothalamic -pituitary circulatory system?
(4 marks)
watch video on this to clarify!!!
- Hypothalamic neuron receives signal hormones go into primary plexus of closed portal system that connects hypothalamus with AP
- Hormones then go down to portal vessel to secondary plexus and move via fenestrations into extracellular space in vicinity of AP cells containing AP hormones
- GHRH binds to its receptor (GHRH-R) a GCPR on somatrophs of AP and increases cAMP which causes increased synthesis of GH
- GHRH stimulates proliferation of these cells through activation of MAP kinase pathway