Endocrinology - Exam 1 (Posterior Pituitary Hormones -- ADH & Oxytocin)

What gland lies in the sella turcica of the sphenoid bone at the base of the brain, just below the hypothalamus with a posterior lobe, anterior lobe, and the infundibulum?

Pituitary Gland

(Hypophysis)

NOTE: Know both names

Which lobe of the pituitary gland does NOT produce any hormones of its own, but rather it stores (2)/secretes hormones made in hypothalamus?

Posterior Lobe

(Neurohypophysis)

What is the posterior lobe (neurohypophysis) derived from? What embryological tissue?

DOWNGROWTH of diencephalon

-- derived from neuroectoderm

Which lobe of the pituitary gland receives signaling molecules from the hypothalamus, has 5 different cell types, and synthesizing/secrete 7 important hormones?

Anterior lobe (Adneohypophysis)

What is the anterior lobe (adenohypophysis) derived from?

UPGROWTH of oral ectoderm of the primitive oral cavity (Rathke's pouch)

What is the stalk between the hypothalamus and the pituitary gland?

Infundibulum

What is the pathway through with hormones travel from the hypothalamus to be stored in the posterior pituitary? (4)

Synthesized in cell bodies located in hypothalamus --> travel down axon --> stored in nerve terminals of Post Pituitary --> cell bodies stimulated, neurosecretory vesicles (Herring bodies) released & secreted into blood

What are the only 2 hormones that are produced by the hypothalamus and secreted by the posterior pituitary?

ADH (Antidiuretic hormone/Vasopressin)

Oxytocin

What nucleus of the hypothalamus secretes ADH? Oxytocin?

ADH = Supra-optic nucleus

Oxytocin = Paraventricular nucelus

What type of hormones are ADH & Oxytocin?

Peptide hormones

Which hormone released by the Post. pituitary acts on the collecting ducts of the kidney to facilitate the reabsorption of water into the blood?

ADH/Vasopressin

Which hormone released by the Post. Pituitary is one of the few hormones to create a positive feedback loop?

Oxytocin

What two factors controls the release of vasopressin/ADH from the posterior pituitary?

1) Decrease in blood volume or low blood pressure (Baroceptor)

2) Increase in blood osmolality; aka dehydration (osmoreceptors)

What are the three effects of the ADH/vasopressin?

1) INCREASE blood volume and blood pressure

2) DECREASE blood osmolality

NOTE: This is the opposite of what triggers it, which makes logical sense as you'd want to fix the issue triggering the response

Where does ADH/vasopressin act (it's target cells)?

Tubular cells of kidney (Principal cells)

What is the primary effect of ADH/vasopressin? What is the secondary effect?

Primary --> INCREASE water reabsorption (from tubules of kidneys back to blood)

Secondary --> CONSTRICITON of blood vessels which therefore INCREASE blood pressure by increasing peripheral resistance

NOTE: hints the name "vasopressin" since its pressin' on that vasculature/vessel

Does ADH/vasopressin use a primary or secondary messenger? Which mechanism does it use?

Secondary (since they're both peptide)

-- Uses Adenylyl cyclase mechanism (cAMP) for the PRIMARY effect

-- Uses Phospholipase C Mechanism (IP3/Ca/DAG) for the SECONDARY effect

What is the primary action of ADH? How does the mechanism for the primary action of ADH/vasopressin work? (3)

Major action to increase water permeability of principle cells in distal tubules of collecting ducts

- ADH receptor = V2 receptor

- Second messenger = cAMP

- Aquaporin 2 will increase the water permeability, allowing water to be reabsorbed by collecting ducts

When there is hypovolemia or hemorrhage, there is a drop in blood pressure which activates what hormone?

ADH/vasopressin

(Secondary action)

T/F: Even at low concentrations, ADH acts on the smooth muscles of blood vessels and leads to vasoconstriction.

FALSE

- only in HIGH concentrations

What is the secondary action of ADH? How does the mechanism for the secondary action of ADH/vasopressin work? (4)

Cause contraction of vascular smooth muscle (when there's a drop in blood pressure - Hypovolemia or Hemorrhage)

- ADH receptor = V1 receptor

- Second messenger = DAG, IP3, Ca2+

- Facilitate actin-myosin interactions by increasing intracellular Ca (activation of receptor-operated Ca channels, voltage gated Ca, PKC channels, eptying intracellular Ca stores)

- Vasoconstriction occurs

The overall effects of ADH by reabsorbing water from tubules into the blood include ____________ blood volume and ___________ blood pressure; ___________ the solute concentration, therefore ____________ plasma osmolarity, ____________ urine volume and finally ____________ urine concentration.

INCREASES blood volume

INCREASES blood pressure

REDUCE solute concentration

DECREASES plasma osmolarity

DECREASE urine volume

INCREASE urine concentration

What pathology is the decreased OUTPUT of antidiuretic hormone (ADH), resulting in a deficiency of ADH, that can be caused by insufficient release by the hypothalamus or by pituitary (MC) release into blood stream?

Central Diabetes Insipidus

NOTE: Has NOTHING to do with blood sugar level; "diabetes" just means a pathology that leads to more urination

What are the signs and symptoms of Central Diabetes Insipidus? (4)

1) Polyuria (frequent urination)

2) Dilute urine (decreased urine concentration)

3) Hypotension (decreased plasma volume and blood pressure decreases)

4) Increased plasma concentration (dehydration)

How does the body try to compensate with Central Diabetes Insipidus? Why is this so important?

Due to ADH decrease (can't absorb water), we compensate by having an increase Aldosterone (maintains blood pressure) to reabsorb the sodium (in which water follows)

-- Reason is because blood pressure drops and body tries to restore it to normal

What is the function of aldosterone during compensation in Central Diabetes Insipidus?

Aldosterone secretion increases

1 - Acts on distal tubules and collecting ducts of kidneys to increase renal reabsorption of sodium (& excrete hydrogen/potassium)

2 - Water follows the sodium

3 - Increase blood volume & blood pressure (bringing blood pressure back to normal)

What is the most crucial electrolyte to stay balanced? What does this have to do with the aldosterone mechanism in Central Diabetes Insipidus?

Potassium

- Moves from blood into renal tubule, putting into hypokalemic state

- As potassium travels down renal tubule later in collecting duct (alpha intercalated channels), the potassium reabsorbed in exchange for H (if needed)

T/F: Reabsorption is the movement of water form the blood to the renal tubule.

FALSE

Blood to renal tubule = Secretion

Renal tubule to blood = Reabsorption

Where is aldosterone produced? What type of hormone is it?

Outer layer of the Adrenal Cortex (zona glomerulosa)

- Steroid hormone (derived from Cholesterol)

(needs transport protein, finds receptor intracellular)

What system stimulates the production of aldosterone?

Renal Angiotensin Aldosterone system (RAAS)

What is the RAAS (Renal Angiotensin Aldosterone System) mechanism? (7 steps)

1) Kidney senses low blood pressure (and decreased blood volume)

2) Kidney secretes hormone RENIN

3) Protein ANGIOTENSINOGEN is secreted by the liver and is present at all times in circulation

4) Renin from kidney cleaves Angiotensinogen and converts it into ANGIOTENSIN I (AT1)

5) ACE (angiotensin converting enzyme) which is secreted by the lungs, converts AT1 to AT2 (ANGIOTENSIN 2)

6) AT2 binds to & STIMULATES conversion of cholesterol into ALDOSTERONE in zona glomerulosa (outer layer of adrenal cortex)

7) Aldosterone travels to the kidneys to REABSORB Na+ & H2O

Central Diabetes Insipidus SUMMARY:

Problem = ADH DECREASED

Plasma (blood) - Pre compensation:

- Plasma Volume DECREASED

- Solute concentration INCREASED

- Blood Pressure DECREASED

Urine - Pre compensation:

- Polyuria INCREASED

- Solute concentration DECREASED (diluted)

Plasma - Aldosterone Compensation:

- Sodium & Water REABSORBED

- Blood Volume INCREASED

- Blood Pressure INCREAED

Urine - Aldosterone Compensation:

- Potassium SECRETION (worried about this -- if body cannot afford to lose it we become hypokalemic; reabsorbed in exchange for hydrogen by alpha intercalated cells)

- Hydrogen SECRETION (not worried about this we can afford to lose this)

What pathology is an abnormality in the kidneys that decreases the sensitivity to ADH in principle cells of collecting ducts, therefore INCREASING secretion of ADH from pituitary, but kidneys do NOT recognize ADH? What does this cause the kidney to not be able to do?

Nephrogenic Diabetes Insipidus

-- Kidney cannot concentrate urine

NOTE: this is a receptor problem not production/secretion

What is the difference between central diabetes insipidus and nephrogenic diabetes insipidus?

Central: Something centrally going on (hypothalamus or pituitary); under secretion of ADH; NOTHING wrong with kidney

Nephrogenic: Issue with the KIDNEY; nothing wrong with hypothalamus/pituitary (making and secreting ADH just fine)

What are the signs/symptoms of Nephrogenic Diabetes Insipidus? (5)

1) Polyuria

2) Dilute urine (decreased urine concentration)

3) Hypotension (decreased plasma volume)

4) Increased plasma concentration (solute level goes up, water goes down; dehydration)

5) ADH LEVELS ELEVATED in the blood

NOTE: SAME exact symptoms as Central Diabetes Insipidus, EXCEPT, ADH levels elevated (NOT decreased)

What may damage the principle cells of the collecting duct in the kidney, resulting in the nephrogenic diabetes insipidus? (3)

1) Drugs --> lithium

2) Hereditary --> X chromosome

3) Treatment with thiazide diuretics --> decrease urine volume

What is a condition in which there is EXCESSIVE release of ASH, usually from an autonomous site (typically a tumor) causing fluid overload in patients due to excess water reabsorption?

Syndrome of inappropriate antidiuretic hormone secretion (SIADH)

SIADH ________ blood volume and _________ blood pressure? What happens to the plasma sodium?

INCREASE & INCREASE

(hypervolemia)

Dilute plasma sodium (Hypoatremia)

What happens to the urine in SIADH?

Urine super concentrated (inappropriately concentrated)

What is SIADH treated with?

ADH antagonist (Demeclocycline or water restriction)

What are 4 possible causes of SIADH (syndrome of inappropriate antidiuretic hormone secretion)? Which is extremely dangerous in this condition if it is not resolved?

Causes:

1) Strokes

2) Head trauma

3) Brain tumors

4) Cancer

DANGEROUS: Cerebral edema

What is the site of synthesis for Oxytocin? What kind of hormone is Oxytocin?

PARAVENTRICULAR nuclei of the hypothalamus

(some in supraoptic nuclei)

Polypeptide protein

Does Oxytocin use a primary or secondary messenger? What mechanism does it use? What type of receptor does it use?

Uses Secondary messenger (since protein hormone)

-- Phospholipase C (DAG, IP3, Ca)

Transmembrane receptor

What is the primary function of oxytocin? (2)

1) Stimulates uterine contractions & cervix dilation

-- toward end of pregnancy, synthesis of oxytocin receptors in uterus increases (before then, not high expression)

-- positive feedback mechanism throughout childbirth

-- contractions push fetal head toward cervix; cervical stretching stimulated

-- Helps reduce post-partum bleeding

2) Necessary for milk ejection reflex (let-down) in breastfeeding women

-- sensory receptors in nipples transmit signals to hypothalamus to secrete/release oxytocin and eject milk

-- suckling NOT required; conditions can be sight, sound, smell

NOTE: This is just for FIRST MILK LETDOWN; prolactin is for continued breast feeding or lactogenesis

What is the secondary function of oxytocin? (2)

1) Parent-newborn bonding (Males and Females)

2) Feelings of love and closeness

aka: LOVE hormone

What are 8 possible roles of oxytocin?

1) Signaling uterus contractions in labor (Women)

2) Milk-letdown (Women)

3) Moving sperm (Males)

4) Testosterone production

5) Bonding hormone (Males & Women)

6) Sexual response

7) Orgasm

8) Social interaction

How does oxytocin work as a social hormone?

Produce feelings of trust and empathy, levels in body increase when we hug someone; experience pleasant physical touch or even pet our pets