Endocrine 2 - Posterior Pituitary

Location of pituitary gland

Ventral part of brain (base), nearby the hypothalamus

What is the hypothalamus made of

Cluster of neurons - distinct nuclei

2 components of the pituitary gland

Adenohypophysis (anterior) - non neural tissue

Neurohypophysis (posterior) - neural tissue

What does the posterior pituitary develop from

Downgrowth of tissue from brain (neural extension)

What does the anterior pituitary develop from

Rathke's pouch

Are hormones produced in the posterior pituitary?

NO! they are secreted here but produced in the hypothalamus

Where in the hypothalamus are hormones produced

Supraoptic + Paraventricular nuclei

Infundibulum

A stalk that attaches the pituitary gland to the hypothalamus.

What hormones are secreted by the posterior pituitary?

ADH/Vasopressin and Oxytocin

Where is ADH produced

Supraoptic nuclei (SON) in hypothalamus

Where is Oxytocin produced

Paraventricular nuclei (PVN) of hypothalamus

What type of hormones are the hypothalamus hormones

Protein hormones

How are protein hormones synthesized

by translation on membrane bound ribosomes - synthesizes the pre-pro-hormones

Synthesis of ADH (steps)

1. RNA translation produced the pre-prohormone, consisting of pro-pressophyrin

2. ADH is bound to neurophysin (intraneural binding protein). This is transported down to neuron axons and vesicles

3. When released, ADH splits from neeurophysin and moves into blood

What two actions does ADH have

Vasoconstriction action and Anti-diuretic actions

Vasoconstrictive action of ADH

- Contracts blood vessel smooth muscle

- Increases blood pressire

- High levels of ADH prevent hemorrhage (constricts muscle)

Antidiuretic action of ADH

- Increases permeability of renal collecting duct by increasing number of water channels

- Vasoconstriction reduces GFR

- Contraction reduces the size of glomerulosa cells, reducing SA for filtration

Mechanism of ADH action

1. ADH travels from posterior pituitary to kidneys and binds to receptor

2. ADH binding induces cAMP production

3. cAMP activates PKA, which upregulates Aquaporin II duct in collecting tubule

4. More water is reabsorbed

What are the 2 main factors that affect secretion of ADH and Vasopressin

1. Plasma volume

2. Plasma osmolality

What osmoreceptors are used to regulated ADH secretion

Hypothalamus cells; supraoptic nucleus and paraventricular nucleus

How do baroreceptors impact ADH scretion

Baroreceptors sense changes in BP based on degree of wall stretching. BP is proportional to osmolality (blood volume)

Location of the baroreceptors and where they connect to

Aortic arch and carotid sinus - stimulus goes to hypothalamus

Regulation of ADH secretion via baroreceptors

1. Decreased blood volume is sensed by baroreceptors

2. Baroreceptors decrease activity in inhibitory afferents to hypothalamus

3. Increased hypothalamus release and PP release of ADH.

4. ADH acts on collecting duct to reabsorb more water to increase BP

Regulation of ADH secretion due to increased blood osmolality

1. Osmoreceptors of hypothalamus (SON, PVN) sense increased blood osmolality

2. Posterior pituitary releases more ADH

3. Kidneys retain more water, returning osmolality to normal

Effect of dehydration on ADH secretion

1. Dehydration cause decreased extracellular fluid volume and increased osmolality

2. Baroreceptors sense decreased blood volume, osmoreceptors sense increased osmolality

3. ADH released from posterior pituitary

4. Plasma ADH increases to increase collecting duct water permeability, more water is reabsorbed and less secreted

5. Osmoreceptors also signal thirst, causing increased water intake

Effect of high amount of ingested water on ADH secretion

1. Increased water causes increased extracellular fluid volume and decreased osmolality

2. Baroreceptors sense increased BP, and inhibtory afferents act on the hypothalmus to release less ADH. Osmoreceptors also sense osmolality and lead to less ADH secretion

3. Less ADH = decreased collecting duct water permeability = increased water secretion

4. Fluid volume returned to normal

Relationship between plasma osmolality and plasma ADH

Linear releationship. As osmolality increases, ADH increases

Relationship between decline in MAP and plasma ADH

Log scale, but linear relationship. When MAP declines, ADH is secreted. Causes vasoconstriction from ADH to increase BP

Non water factors of increased ADH secretion

- Stress/emotion

- Heat (save water as we lose it through sweat)

- Nicotine

- Caffeine (at kidney - blocks ADH action, but increases secretion at hypothalamus)

Non water factors of decreased ADH secretion

- Cold

- Alcohol

Main pathogenic issue of ADH deficienct

Diabetes insipidus

Hypothalamus/central diabetes insipidus

No ADH production/release

Nephrogenic diabetes insipidus

No ADH action (problem with receptors or intracellular signaling)

Main pathogenic issue of ADH excess

Syndrome of Inappropriate ADH (SIADH)

Syndrome of Inappropriate ADH (SIADH)

Problem of ADH production or feedback failure

Symptoms of diabetes insipidus

Polyuria - production of large amounts of dilute urine

Polydipsia - excessive thirst and fluid intake

Unable to decrease urine flow even when water deprived

How to treat Central diabetes insipidus

Desmopressin - synthetic ADH

How to treat nephrogenic diabetes insipidus

Other antidiuretics that aren't ADH

Mechanism of SIADH

Excessive ADH causes excessive water retention. This increases GFR and decreases aldosterone

- Decreased aldosterone prevents na+ reabsorption, causing hyponatremia

- Decreased osmolality as well

Oxytocin actions on the uterine myometrium

- Parturition (not a requrement but it helps)

- Clamps rupture blood vessels from hemorrhage

- Restores uterine size after child birth

- Stimulates sperm movement

- Stimulates cervix movement ("sucks up sperm")

Oxytocin actions on mammary myometrium

Milk let down

What kind of feedback does oxytocin have

Positive

Oxytocin feedback loop of parturition

1. Uterine contractions push fetus toward cervix

2. Fetus on cervix sends message to release oxytocin

3. Acts on uterine myometrial layer to cause more contractions

4. Repeats until fetus comes out of cervix

Oxytocin positive feedback loop of milk-let down

1. Suckling of nipple increases oxytocin release

2. myoepithelial cells to contract on milk secreting epithelial cells

3. Milk released into lumen and can be ejected from nipple

Conditioned response of milk let down

Visual and auditory stimuli related to infant can stimulate milk let down

Non-maternal functions of oxytocin

1. Released during sexual intercourse and stimulates orgasm

2. Increased in social bonding

Oxytocin function on male reproductive function

Action unknown, possible aid in sperm release and erection

How is oxytocin secretion increased

Tactile stimulation of genital tract (parturition, orgasm), or nipples (milk let down)

How is oxytocin secretion decreased

Psychogenic/physical: Stress can cause difficulty with lactating

Impacts of oxytocin deficiency

- Impaired child delivery (but not required)

- Impaired lactation (not a problem if access to baby formula)

Impacts of oxytocin excess

No issues seen