Lecture 6: Posterior Pituitary Flashcards by Emma Djabali

What is the main type of neurons in the post pit? Describe them.

Magnocellular neurons: large and contain sulfur (through cysteine)

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From what 2 hypo nuclei do the magnocellular neurons of the post pit originate from?

Paraventricular

2. Supraoptic

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Describe the characteristics of the magnocellular neurons of the post pit.

Slow and high affinity: meaning they release hormones slowly but a very slight stimulus will cause them to release hormones because these are released in small quantities in the whole blood stream so concentrations are very small

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What are the 2 neurohormones released by the magnocellular neurons of the post pit?

Oxytocin

2. Vasopressin (ADH)

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What is the role of oxytocin?

Uterus and mammary glands contraction of smooth muscle

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What is the role of ADH?

Reabsorption of water in kidney tubules to decrease plasma osmolality and concentrate urine

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What kind of hormones are oxytocin and vasopressin? Therefore, where are they secreted?

Nonapeptides (9 AAs): hydrophilic so secreted directly into blood

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How closely related are oxytocin and vasopressin? 3 arguments.

Share 7 out of 9 AAs (differ at 3rd and 8th positions)
Arise from same progenitor: vasotocin
Located on same chromosome and inverted (probably evolved through gene duplication)

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What protects oxytocin and vasopressin from degradation by enzymes? Why is this important?

Carboxy end protected by AMIDATION: amide group left over from peptide bond cleavage to glycine that is not recognized as the carboxy-end by enzymes
Amino end protected by DISULFIDE BOND: forms a cyclic structure

Important because we have very low concentrations in the blood

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What are 5 kinds of enzymes that degrade peptides?

Proteases
Exonucleases
Amino-peptidases
Carboxy-peptidases
Endopeptidases

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What are both oxytocin and vasopressin synthesized as? Why?

Inactive precursors that are later cleaved

Purpose: to have the carboxy-end protected from enzyme degradation

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What are the 3 vasopressin receptors?

Vasopressin V2
Vasopressin V1a
Vasopressin V1b

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Where is Vasopressin V2 located? How does it work?

Location: kidney (distal and collecting tubules)

Allows for vasopressin to function as ADH to reabsorb water

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What does ADH stand for?

Anti-diuretic hormone

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Where is Vasopressin V1a located? How does it work?

Location: vasculature of CNS, smooth muscle, and liver
Acts as a vasoconstrictor:
1. PLC-beta degrades membrane phospholipids into DAG and IP3
2a. DAG stimulates PKC to stimulate contraction
2b. IP3 travels to ER to release calcium to stimulate contraction

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Where is vasopressin V1b located? How does it work?

Location: corticotrophs of ant pit

Works with CRH to release ACTH

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Which neurohormone is the dominant regulator of ACTH?

CRH

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Where are oxytocin receptors located? 2 locations

Uterus: myometrium

2. Mammary glands: myoepithelium (smooth muscle)

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What is the role of osmoreceptor afferent magnocellular neurons?

Regulate vasopressin secretion by post pit when plasma osmolality increases

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What are the 2 types of magnocellular neurons?

Osmoreceptor afferent

2. Non-osmoreceptor afferent

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What is the role of non-osmoreceptor afferent magnocellular neurons?

Baroreceptors/volume receptors in carotid and aortic circulation to inhibit vasopressin secretion when BP or BV is too high

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How do the osmoreceptor afferent magnocellular neurons detect high blood osmolality? How sensitive are they?

When body is hyperosmolar the fenestrations of hypo let solute go through, this shrinks the cells that have fenestrations and activates the magnocellular neurons
VERY sensitive: respond to changes in osmolality of less than 1%

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How would you characterize the osmotic regulation of vasopressin secretion?

Linear: increases as osmolality increases AT ANY BP!

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How is urine osmolality affected by an increase in vasopressin secretion?

Increase in urine osmolality

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What is the osmotic threshold?

The plasma osmolality threshold before vasopressin secretion = 280 mosm/kg

Equation to calculate vasopressin plasma concentration?

[AVP]p = 0.3 x (Posm - 280)

What is the plasma osmolality of a normally hydrated person?

287 mosm/kg

What is the plasma concentration of vasopressin of a normally hydrated person?

2.0 pg/mL

What is the urine osmolality of a normally hydrated person?

500 mosm/kg

Does duration of urination change with body size?

NOPE

What % increase in TBW causes maximal dilution of plasma vasopressin concentration and urine osmolality?

What % decrease in TBW causes maximal concentration of urine osmolality? What is max concentration of urine?

2% Max Uos > 1000 mosm/kg

What is the plasma concentration of vasopressin at maximal antidiuresis? Can it increase beyond that?

5 pg/mL | Yes, but this will have no effect on reabsorption of water in kidney

What happens to increase TBW once maximal antidiuresis has been reached?

THIRST!

How does drinking water affect vasopressin secretion? How? When? Purpose?

It inhibits it BEFORE CHANGES IN FLUID VOLUME OR OSMOLALITY by cold-sensitive oropharyngeal receptors being activated Purpose: to ensure we are not overhydrated

How does increasing BP influence the linear curve of vasopressin concentration vs plasma osmolality? Explain what this means.

The slope decreases making the osmotic threshold greater => this makes it more difficult for vasopressin to regulate plasma osmolality at high BP

What is the relationship between vasopressin concentration and mean arterial pressure (MAP)?

Exponential

What is the most powerful regulator of vasopressin concentration?

Hemorrhage aka BP

What is the most important regulator of vasopressin concentration?

Osmotic regulation

Describe the 8 steps that happens when vasopressin binds the V2 receptors?

1. Vasopressin binds V2 on basolateral membrane 2. Gas activation 3. Adenylyl cyclase activation 4. cAMP synthesis 5. Protein kinase A activation 6. Phosphorylation of vesicles in cytoplasm that contain aquaporins (AQP-2) 7. Insertion of aquaporins into apical membrane to reabsorb water 8. Water pumped back into the cell and then interstitial space via the AQP3 and 4 aquaporins of the basolateral membrane

What kind of transport happens through aquaporins?

Facilitated diffusion

What are the 8 ways in which the body regulates fluid electrolytes and BV?

1. RAA system 2. Adrenergic NS 3. Vasopressin 4. Atrial netriuretic hormone (ANP) 5. Kinins 6. Endothelins 7. Prostaglandins 8. Nitric oxide system

What is diabetes insipidus characterized by?

Low BV and large dilute urine volume

What are the 4 types of diabetes insipidus? What is the treatment for all of them?

1. Central = neurogenic = hypothalamis 2. Nephrogenic 3. Dipsogenic 4. Gestational Treatment: long-lasting vasopressin agonist (snorted)

What is central/neurogenic diabetes insipidus due to? Overall and 6 causes?

Inability to synthesize or secrete active vasopressin: 1. Metastatic tumor 2. Idiopathic 3. Histiocytosis (immune related) 4. Severe whiplash that severes the pituitary stalk 5. Genetic 6. Anatomical defect

What is nephrogenic diabetes insipidus due to?

Inability of kidney to detect vasopressin: usually V2 or aquaporin receptor (AQP2) mutation

What is dipsogenic diabetes insipidus associated with?

Excessive water drinking linked to psychiatric disorders: schizophrenia with over consumption of water

What is gestational diabetes insipidus due to?

Placenta secretes vasopressinase that degrades vasopressin

What is the effect of oxytocin on men?

Pair-bonding, fidelity and trust

What is the suckling pathway of oxytocin production?

Infant sucks on boob stimulates reflex loop that synapses at spinal cord with hypo neurons which stimulates oxytocin secretion causing milk ejection

What is the visual stimulus pathway of oxytocin production?

Woman sees, hears, or smells a crying baby it will stimulates oxytocin secretion causing milk ejection

Where is milk ejected after oxytocin secretion?

Lumen of mammary gland

How is uterine contraction stimulated during labor?

Increase in expression of oxytocin receptors in the myometrium

How is uterus stretching stimulated during labor? 4 steps

1. PLA2 and PLC are activated (PLC normal pathway) 2. PLA2 produces arachidonic acid 3. Arachidonic acid stimulates prostaglandin production: PGE2 and PGF2alpha 4. Prostaglandins soften uterus

What is atosiban? What has been figured out about it?

Oxytocin antagonist that is ineffective at delaying labor because oxytocin only plays a minor role

What is adoptive breastfeeding?

The stimulation of breast enlargement and milk ejection without labor

What is tocolysis?

The delaying or inhibition of labor during the birth process

Why has pair-bonding become evolutionarily adaptive?

Because with pair-bonding you have a longer life-span, more intimacy (inversely correlated with negative psychological states, such as depressed mood, and positively correlated with immune function and cardiovascular health), and more paternal involvement leading to improved well-being of children

What is the effect of vasopressin and oxytocin when secreted centrally in the brain?

Important for pair-bonding

How do prairie and montane voles differ? Why?

Prairie voles share nests, take care of children, have monogamous relationships and montane voles do not, this is because prairie voles have more V1a receptors

What part of the human V1a receptor is associated with fidelity and pair-bonding? What does a specific allele lead to?

The RS3 region | Allele: decreased likelyhood of marriage, happy relationships, and happy partner

How does [AVP]p increase when there is a 2% TBW decrease?

Increases: x2

Describe the sensitivity of the ADH and oxytocin receptors?

VERY sensitive because concentration in the blood is so low

What enzyme cleaves the amide group protecting the carboxy end of oxytocin and vasopressin?

A signal peptidase in the ER

What type is the V2 vasopressin receptor?

G alpha S protein coupled receptor: adenylyl cyclase activation

What does stimulation of the V1a receptors cause? Inhibition?

Gq stimulation: Activation of phospholipase C | Gi inhibition: Activation of adenylyl cyclase

What does stimulation of the oxytocin receptors cause?

Gq receptors: 1. Activation of phospholipase C 2. PLC degrades membrane phospholipids into DAG and IP3 3a. DAG stimulates PKC to stimulate contraction 3b. IP3 travels to ER to release calcium to stimulate contraction

What are the 2 most important fenestrations for the osmoreceptor afferent magnocellular neurons of the hypothalamus?

1. OVLT | 2. SFO

What is the plasma concentration of vasopressin prior to osmotic threshold being reached?

~0.5 pg/mL

What does a 0.3 difference in Pavp cause? What does this mean?

A 3 L difference in urine volume over 24 hours with half the osmolality! Very small changes in Pavp have huge consequences

What is the osmotic threshold of thirst osmoreceptors? How does this compare to the osmotic threshold of vasopressin secretion? Why?

285-290 mosm/kg (higher than the vasopressin osmotic threshold) Because our body can handle small changes in osmolarity, we have a whole system for that, might as well use it.

What is a volitional control or incentive behavior? What is an example?

Cognitive process by which an individual decides on a particular course of action Drinking or putting on a sweater when I'm cold

What types of people do not feel thirst as much?

Old people

Why do we prefer to drink cold water?

Because our oropharyngeal receptor will be better satisfied and thirst will be better satisfied

What does volemia mean?

Tension

What are the 2 parts of the kidney collecting duct that contain V2 receptors?

1. Cortical collecting duct | 2. Inner medullary collecting duct

What regulates oxytocin secretion? 3 factors

1. Osmotic regulation 2. Suckling at nipple 3. Sex 4. Hearing/seeing/smelling a crying baby

Which is the strongest oxytocin secretion regulator?

The first cry of a baby

Why don't increases in oxytocin induce labor?

Because it's the increase in the number of receptors that really causes labor

What is the only difference between the mammary and uterine oxytocin receptors?

In uterus PLA2 is also activated, in mammary glands only PLC beta is

What drugs can be used to help adoptive breastfeeding? How does each work?

1. Domperidone/Metoclopramide/Sulpiride/Chloropromazne: blocks pituitary dopamine receptors 2. TRH: directly stimulates lactotrophs (PRL)

What 3 things is pair-bonding characterized by?

1. Partner preference 2. Mate-guarding 3. Bi-parental care of young

What does parturition mean?

Labor