Neuropeptides and Hormones

Question 1

What are neuropeptides?

(2 marks)

Answer 1

• Small proteins produced by neurons
• Act on GCPRs and responsible for slow onset, long lasting modulation of synaptic transmission

Question 2

What are the two families of neuropeptides?

(2 marks)

Answer 2

• Small molecule NT: GABA, glutamate etc,
• Peptide NT: range of brain and gut peptides (in particular hypothalamus)

Question 3

Name some of the mammalian neuropeptides:

(5 marks)

Answer 3

• Opioids
• Pituitary peptides
• Hypothalamus releasing peptide
• Peptide neurotransmitter
• Brain-gut peptides

Question 4

How is proopiomelanocortin (POMC) produced in the secretory granule?

(9 marks)

Answer 4

• 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

Question 5

In cows, why does the relative expression of Kiss/Dyn change?

(2 marks)

Answer 5

• Due to reporoductive cycle
• BUT can be co-expressed in neurons and secretoru granules that contain both of them

Question 6

What is the difference in function between G proteins GHRH and SRIF?

(2 marks)

Answer 6

• GHRH:
  
  • ​Signals through Gαs which activates adenylate cyclase
• SRIF:
  
  • ​Binds to SSTR1-5 receptor and activates Gαi which inactivates adenylate cyclase

Question 7

What loop of the G-protein receptor interacts with the G-protein?

(2 marks)

Answer 7

• 3^rd intracellular loop
• Binding to receptor causes α-subunit to dissociate and activate substrate molecule

Question 8

What does the G protein OXY do?

(4 marks)

Answer 8

• Binds to OTR
• Causes dissociation of Gαq
• Activates PLC and produces IP₃ and DAG
• IP₃ increases intracellular Ca²⁺
• DAG increases extracellular Ca²⁺

Question 9

What is another word for the anterior pituitary?

Answer 9

Adenohypophysis (pars distalis)

Question 10

What is another word for posterior pituitary?

Answer 10

Neurohypophysis (pars nervosa)

Question 11

What is another name for intermediate lobe?

Answer 11

Pars intermedia

Question 13

Outline the basis of posterior pituitary circulation.

(6 marks)

Answer 13

• 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

Question 14

Outline the blood supply for the anterior pituitary.

(6 marks)

Answer 14

• 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

Question 15

Describe what the structures and their location in the picture.

Answer 15

• 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 3^rd 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

Question 16

What hormones are present in the posterior pituitary?

(2 marks)

Answer 16

• Vasporession
• Oxytocin

Question 17

What is the function of Vasopressin?

(2 marks)

Answer 17

• Controls kidney at higher concentrations and can cause vasoconstriction
• Associated with diabetes insipidus-receptor as isn’t responding so get lots of dilute urine

Question 18

What controls the levels of secretion of vasopressin?

Answer 18

Plasma osmality and blood volume

Question 19

What is the function of oxytocin?

(5 marks)

Answer 19

• 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

Question 20

What are the different anterior-pituitary axes?

(5 marks)

Answer 20

1. HP-thyroid
2. HP-adrenal
3. HP-Growth hormone
4. HP-prolactin
5. HP-Gonodal

Question 21

What is produced in the HP-thyroid axis and what does it do?

(5 marks)

Answer 21

• 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

Question 22

What is produced in the HP-adrenal axis and what does it do?

(5 marks)

Answer 22

• 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

Question 23

What is produced in the HP-growth hormone axis?

(3 marks)

Answer 23

• 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

Question 24

What is produced in the HP-prolactin axis and what factors affect its functionand expression?

(6 marks)

Answer 24

• 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

Question 25

What is produced in the HP-gonodal axis? (3 marks)

Answer 25

* **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**

Question 26

How is GnRH stored and secreted? | (3 marks)

Answer 26

* 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

Question 27

What is the basic stages of GnRH migration during neurogenesis? (5 marks)

Answer 27

1. Neurogenesis 2. Initiation 3. Divergence 4. Progression 5. Arrest

Question 28

What is the developmental process of the GnRH system. (9 marks)

Answer 28

* 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

Question 29

What happens in the hypothalamic -pituitary circulatory system? (4 marks) watch video on this to clarify!!!

Answer 29

* 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