Posterior Pituitary Hormones Flashcards
What is ADH also known as?
Antidiuretic hormone and vasopresin
What does the hypothalamus control?
Through which types of signals does it control?
Posterior pituitary hormones
The posterior pituitary hormones are controlled by neuronal signals from the hypothalamus
Where is oxytocin synthesized?
Where is ADH synthesized?
In the cell body of the hypothalamus at the paraventricular nucleus
In the cell body of the hypothalamus at the supraoptic nucleus
What does ADH work on?
What is it packaged with in the posterior lobe of pituitary?
Works on kidney and blood vessels to promote action of water loss inhibition
Neurophysin (NPII)
What does oxytocin work on?
What is it packaged with in the posterior lobe of pituitary?
Works on breast and cervix
Neurophysin (NPI)
What are the two types of receptors for ADH?
What do V1 receptors do?
What do V2 receptors do? Where are they located?
V1 and V2
V1: Mediate vasoconstriction, increased ACTH secretion, and glycogenolysis
V2: Located in principle cells in distal convoluted tubule and collecting ducts in the kidney.
- They are coupled via G proteins to adenylate cyclase or phospholipase C
What differentiates ADH from oxytocin? How are they similar?
They are each made of 9 amino acids and differ by two amino acids
- They differ at amino acid 3 and 8
ADH= Phe & Arg
Oxytocin= Ile & Leu
Which stimulatory factors affect ADH secretion?
- Increased serum osmolarity
- Decreased ECH volume
- These increase ADH secretion because there is less water and more solute in the factors above
- ADH keeps more water inside blood vessels
What is the function of ADH?
Regulation of body fluid osmolarity
What happens when deprived of water?
- Plasma osmolarity increases
- Osmoreceptors in anterior hypothalamus are stimulated
- Increase in ADH secretion from posterior pituitary
- Increase in water permeability of principal cells (late distal tubule and collecting duct)
- Water reabsorption increases
- Urine osmolarity increase and urine volume decreases
- Plasma osmolarity decreases toward normal
What happens when you drink water?
- Plasma osmolarity decreases
- Osmoreceptors in the anterior hypothalamus are inhibited
- Decrease in ADH secretion from posterior pituitary
- Decrease in water permeability of principal cells (late distal tubule and collecting duct)
- Water reabsorption decreases
- Urine osmolarity decreases and urine volume increases
- Plasma osmolarity increases toward normal
Which type of blood osmotic pressure stimulates hypothalamic osmoreceptors?
High blood osmotic pressure
What do osmoreceptors activate? What is secreted?
Hypothalamic neurosecretory cells are activated and ADH is released
From where is ADH secreted?
Nerve impulses liberate ADH from axon terminals in the posterior pituitary gland into the blood stream
Which body organ retains water?
What happens to urine secretion?
Kidneys retain water which decreases urine output
What occurs in sweat glands and arterioles when there is an increase in ADH?
Sweat glands decrease water loss via perspiration from the skin
Arterioles constrict which increases blood pressure
What is the effect of ADH on principal cells in the distal tubule?
- ADH receptor binds to V2 receptors
- Adenylyl cyclase signaling system is activated
- Aquaporin-2 expression on luminal membrane of principal cell increases
- Membrane water permeability increases
What is another way to increase ADH secretion?
What is decreased?
Hypovolemia which is volume contraction due to a hemorrhage
ECF (extracellular fluid) and blood pressure are decreased
What happens during a decrease in blood pressure?
The decrease in BP is sensed by the carotid and aortic baroreceptors and is transmitted via the vagus nerve to the hypothalamus which directs an increase in ADH secretion
What does ADH bind to during hypovolemia?
What is activated?
What is contracted in response?
ADH binds to V1 receptors on vascular smooth muscles.
Phospholipase C signaling system is activated
Vascular smooth muscle is contracted
What does the secretion in ADH do to body fluid?
There is a reduction in body fluid loss and an increase in total peripheral resistance (TPR) to increase blood pressure
What is the pathophysiology of ADH?
- Central diabetes insipidus
- Nephrogenic diabetes insipidus
- Syndrome of inappropriate ADH secretion (SIADH)
What occurs in central diabetes insipidus?
What is damaged?
How is it treated?
- ADH deficiency due to hypothalamus/ posterior pituitary damage
- Collecting ducts are less permeable to water… and produce large volumes of dilute urine -> excessive thirst
- Tx: ADH analogue, dDAVP
What occurs in nephrogenic diabetes insipidus?
What is damaged?
How are the kidneys affected?
What is the overall change in ADH
- Posterior pituitary is normal
- V2 receptors, G protein or adenylyl cyclase in principal cells of the kidney are defective
- Principal cells are unresponsive to ADH
- Water reabsorption by kidney is reduced which produces large volumes of dilute urine
- ADH levels are elevated
What occurs in SIADH?
How are the kidneys affected?
- Excess circulating levels of ADH. ADH is secreted from abnormal sources (oat cell carcinoma of the lungs)
- Excessive water reabsorption by the kidneys; small volume of concentrated urine is produced -> plasma osmolarity is reduced
- Retention of fluid, headaches, and disorientation
What is the primary function of oxytocin?
Milk letdown aka ejection
What are the actions of oxytocin?
- Milk ejection: Oxytocin contracts the myoepithelial cells lining the mammary ducts
- Uterine contraction: Oxytocin is used to induce labor and to reduce postpartum bleeding
How is oxytocin secretion regulated?
Suckling of breast
Dilation of cervix
Conditioned responses
What do the CNS relays from the hypothalamus do?
What triggers the CNS relays?
Supraoptic and paraventricular nuclei cause a release of oxytocin from the posterior pituitary
- Suckling and cervical stretch receptors
What are the effects of oxytocin on child birth?
- Head of fetus pushes against the cervix
- Nerve impulses from cervix are transmitted to brain
- Brain stimulates pituitary gland to secrete oxytocin
- Oxytocin is carried in bloodstream to uterus
- Oxytocin stimulates uterine contractions and pushes fetus toward cervix
What organ does hyperpituitarism affect?
What results in hyperpituitarism? Which is more common?
Anterior pituitary
- Adenomas (Benign)
- Pituitary carcinomas (rare)
- Pituitary hyperplasia
- Overstimulation by hypothalamus
What are the types of adenomas that result in hyperpituitarism?
What are the names of the specific types of anterior pituitary tumors?
Single or plurihormonal
Micro or macroadenomas
Somatotroph adenoma, corticotroph adenoma, Thyrotroph adenomas, Gonadotroph adenoma
What is the morphology of a hypersecreting adenoma?
- Circumscribed lesions
- Confined to sella turcica
- Tumors are made of uniform cells with calcification and granule formation
- Tumors lack reticulin (CT)
What can pituitary adenomas result in?
What do they impede on?
Which nasal fibers are affected?
What is the overall change in vision?
Breaking of blood vessels which poses a problem to vision
- Diplopia
- Ophtalmoplegia
- Optic Atrophy
Impedes on the optic chiasm from below
Inferior nasal retinal fibers are affected
Superior bitemporal vision loss
How does vision loss correlate with field defects?
If the field defects are asymmetric then visual field loss is asymmetric
What is ophthalmoplegia?
Paralysis of EOMs that control eye movements
If you have optic atrophy will your vision recover?
NO, you would have to remove adenoma from pituitary and still have vision loss
What results in hypopituitarism?
- Defects of hypothalamic or intrinsic pituitary deficit
- Destructive processes involving the anterior pituitary.
- 75% of the pituitary parenchyma has to be involved
Where is the thyroid gland located?
What is the structure?
What are the lobes made of?
Wrapped around the trachea below the Adam’s apple
Right and left lobes connected by isthmus
Thyroid follicles and parafollicular cells
What occurs at the thyroid follicles?
What are thyroid follicles made of?
Thyroid hormone synthesis
Inner colloid has newly synthesized thyroid hormones attached to thyroglobulin
Outer layer has cells that produce glycoprotein: THYROGLOBULIN
What do follicular cells have that make them specific?
What do they do?
Receptors for Thyroid stimulating hormone (TSH) -> initiate cascade for release of thyroid hormones into blood
What is the biochemistry of thyroid hormone?
What is the essential element?
Can it cross the cell? Why?
They are Amines made from tyrosine
Iodine, you need it to make thyroid hormones
Yes, they can cross because they are hydrophobic.
What are the subtypes of thyroid hormone?
Which are functional?
Which has higher affinity?
Which is used predominantly? What happens with it?
Which is biologically active?
T3, T4, rT3
T3, T4
T3
T4 and made more than T3. T4 crosses and is converted into T3 in the cells via 5’- iodenase
T3
What are the mechanisms of action of thyroid hormone?
- Hydrophobic molecule thus it can cross into any cell
- Modifies the activity of target tissue by binding to nuclear receptors thus it activates nearly every tissue in the body
Where is thyroglobulin synthesized? Where does it then go?
Thyroglobulin is synthesized by rough ER and secreted into the colloidal lumen via exocytosis
Where is iodide transported? How?
Which type of transportation is used?
Iodide is actively transported from the blood into the follicular epithelial cells across the basolateral membrane. Pump activity is inhibited by perchlorate and thiocyanate
Active Na transportation
Does iodide get into the cell? What happens once it enters?
How is activity blocked?
Iodide traverses the cell to the apical membrane and into the colloidal lumen where it is oxidized to iodine in the lumen by the enzyme thyroid peroxidase.
Thyroid peroxidase activity can be blocked by propylthiouracil
What is iodinated? Which enzyme is used?
What is this process called?
Tyrosine residues of thryoglobulin are iodinated to form monoiiodotyrosine (MIT) and Diiodotyrosine (DIT)
Enzyme: Thryoid peroxidase
AKA: Organification of thyroglobulin
What do coupling reaction occur between?
What is created?
Which enzyme is used?
Which reaction is faster?
Coupling reactions occur between MIT/DIT or between DIT/DIT
T3 & T4 created
Enzyme: Thyroid peroxidase
The 2nd rxn is faster thus there is more T4
What happens to the follicular cells when stimulated?
What are they stimulated by?
Stimulant: TSH
Thyroglobulin complex is endocytosed by follicular epithelial cells
What is cleaved by the thyroglobulin complex?
Which type of mechanism is used?
Where is it secreted?
T3, T3, MIT, DIT are cleaved
Proteolytic mechanism
Secretion into the blood
What is deiodinated?
Where does deionation occur?
Which enzyme is used?
Where is it recycled to?
MIT/DIT deiodinated
Occurs in follicular cells
Enzyme: Thyroid deiodinase
Recycled into intracellular pool
What is thyroid hormone bound to?
If it is bound what happens?
Bound to plasma proteins (Thyroxine binding globulin- TBG)
It is inactive when bound thus it can’t cross membrane
What alters free thyroid hormone levels?
Which state reduces thyroid hormone levels?
Which state increases thyroid hormone levels?
Changes in blood levels of TBG alter free thyroid hormone levels
Hepatic disease- TBG reduces and total thyroid hormone levels reduce because it was high before
Pregnancy: TBG increase and total thyroid hormone level increases because it was low before
What is the free unbound state?
T3 & T4
What happen when T4 is activated?
Which is most active?
Which is produced more?
When activated T3 is converted to T3 via 5’-iodinase in target tissue
T3 is most active
T4 is produced in abundance 10x more
What is special about thyroid hormone in relation to thyroid gland?
Thyroid hormones synthesize and store TH in glands for future use
What does TSH regulate?
Which type of effect is seen?
What does overstimulation of thyroid gland lead to?
Growth of thyroid gland
Trophic effect
Overstimulation of thyroid gland -> thyroid hypertrophy and hyperplasia
Which receptors does TSH activate?
What is the receptor also activated by?
TSH activates a receptor coupled to G protein and adenylate cyclase
Receptor also activated by thyroid stimulating immunoglobulins which are antibodies to TSH receptor
What does hyperthyroidism result from?
What is this disease known as?
Hyperthyroidism results from increased thyroid-stimulating immunoglobulin which leads to an increase in T3/T4
Graves disease
How are TSH levels in Grave’s disease?
Which type of feedback mechanism is displayed here?
TSH levels are low due to high circulating levels of thyroid hormones inhibiting TSH secretion
Negative feedback
How is negative feedback displayed?
What does negative feedback work directly on?
Which hormone is in abundance? What state is it in?
Free T3 mediates the negative feedback effect by downregulating the expression of TRH receptors on thyrotropes
Hypothalamus
T3 in free state
What do thyroid stimulating immunoglobulins activate?
Activate TSH receptors -> T3/ T4 production
What are thyrotrophes?
Endocrine cells in the anterior pituitary that produce TSH in response to thyrotropin releasing hormone
What does the hypothalamus do in thyroid hormone regulation ?
Releases TRH (Thyrotropin Releasing hormone) to the anterior pituitary
What does the anterior pituitary do in thyroid hormone regulation?
Releases TSH to the thyroid gland
What does the thyroid gland do in thyroid hormone regulation?
Releases T3/T4
What happens if there is too much T3/T4?
Negative feedback inhibition by downregulating TRH receptors on the anterior pituitary or directly on the thalamus
What are the actions of thyroid hormone?
- Growth
- CNS
- BMR- Basal metabolic rate
- Metabolism
- Cardiovascular
What is the role of thyroid hormone on BMR?
Which enzyme is used?
Increase in sodium/potassium pump
Increase in oxygen consumption
Increase in heat production
Increase in BMR
ATPase
What is the role of thyroid hormone on metabolism?
What do thyroid hormones increase?
Increase in protein synthesis and degradation
Lipolysis- Triglycerides breakdown into fatty acids and glycerol
Increase glucose absorption form GI tract
What is the role of thyroid hormone on cardiovascular system?
What is induced?
Increase in cardiac output of heart rate & contractility and ventilation
Myosin, B1-adrenergic receptors, Ca2+ ATPase are induced
What is the cardiac output equation?
Cardiac output= heart rate x stroke volume
What is hyperthyroidism?
What is hyperthyroidism also known as?
What are the causes?
Hypermetabolic state caused by elevated T4/T3
Thyrotoxicosis
Causes:
- Pituitary adenomas
- Thyroid adenoma (rare)
- Graves disease
- Thyroid carcinomas
- Neonatal thyrotoxicosis
- Excessive thyroid hormone therapy for hypothyroidism
Why is the effect of a pituitary adenoma on TSH?
The tumor on the pituitary causes too much TSH which leads to an increase in T4. Normally negative feedback would occur but since there is a tumor the result is too much TSH
What are the symptoms of hyperthyroidism?
- Increase BMR
- Weight Loss
- Increased thermogenesis and sweating
- Increased cardiac output and cardio issues
- Goiter: Graves disease
- Multiple ocular manifestations in Grave’s disease
What is treatment for hyperthyroidism?
- Propylthiouracyl: Blocks thyroid peroxidase
- Thyroidectomy: Removes thyroid
- Radiolabeled iodine: Kills thyroid tissue
- B- adrenergic blockers: Cardiovascular complications that inhibit epinephrine
What are the ocular manifestations in Graves disease?
Exophthalmos
Lagophthalmos
Bulbar conjunctiva injected
Corneal Dryness
Ocular misalignment
Diplopia
Compressive Optic atrophy -> visual defects
What are treatments for ocular symptoms of Graves disease?
- Restore normal thyroid status “Euthyroid”
- Sodium/ H2O restriction to reduce edema
- Surgical lid retraction repair
- Prisms or occlusion therapy
- Strabismus surgery
- Orbital decompression
- Eye lubricants
- Steroids
What is a common autoimmune disease that causes hypothyroidism?
What is the best treatment?
Hashimoto’s Thyroiditis
Destroy the thyroid gland
What is hypothyroidism?
Reduced action of thyroid hormone
What are the causes of hypothyroidism?
- Genetic defect
- Post- ablative
- Autoimmune disease
- Iodine deficiency
- Pituitary failure- No TSH= no T3/T4
- Hypothalamic failure
- Thyroid stimulating hormone resistance- receptor not working
What are the symptoms of hypothyroidism?
Decreased BMR
Weight gain
Decreased thermogenesis and cold sensitivity
Decreased cardiac output
Droopy eyelids
Goiter
Myxedema: specific form of cutaneous and dermal edema
What is the treatment for hypothyroidism?
Hormone replacement surgery
