L14 Hypothalamus And Pituitary Flashcards
What hormones are released from the anterior pituitary?
Adrenocorticotropic hormone ACTH
Growth Hormone GH
Thyroid stimulating hormone TSH
Prolactin PRL
Luteinizing hormone LH
Follicle stimulating hormone FSH
What hormones are released from the posterior pituitary?
Oxytocin OT
Arginine vasopressin AVP aka Antidiuretic hormone ADH
What is another name for antidiruetic hormone ADH?
Arginine vasopressin AVP
What are magnocellular neurons?
Large neurons that originate in the hypothalamus that project into the posterior pituitary, where they release their hormones into a capillary bed
(The hormones that are produced by the magnocellular neurons are the final product that get released into the blood!)
Where exactly in the hypothalamus do the magnocellular neurons originate?
Paraventricular nuclei
Supraoptic nuclei
What hormones are released from the magnocellular neurons?
Oxytocin
AVP aka ADH
NP (Neurophysin)
What are the parvicellular neurons?
Neurons that originate in the hypothalamus and extend to a capillary bed in the Median Eminence and release Hypothalamic hormones (releasing or inhibitory)
These hormones then travel down blood vessels into the anterior pituitary where they cause the anterior pituitary to release trophic hormones
What hormones are released into the anterior pituitary by parvicellular neurons?
CRH
TRH
GnRH
GHRH
SS (Somatostatin)
DA (dopamine)
What hormones are released by the anterior pituitary into the systemic circulation?
ACTH
TSH
LH/FSH
GH
PRL
GHRH causes the release of what hormone from the anterior pituitary?
GH
TRH causes the release of what hormones from the anterior pituitary?
TSH
Prolactin
What effect does somatostatin have on the anterior pituitary?
It INHIBITS the synthesis of GH and TSH
GnRH causes the release of what hormones from the anterior pituitary?
LH
FSH
CRH causes the release of what hormone from the anterior pituitary?
ACTH
PRF (prolactin releasing Factor) causes the release of what hormone from the anterior pituitary?
Prolactin lol
What effect does Dopamine have on the anterior pituitary?
It INHIBITS prolactin synthesis
Where are ADH and Oxytocin synthesized?
In the cell bodies of the magnocellular neurons
Which are located in the supraoptic and paraventricular nuclei
What is the half life of ADH and Oxytocin?
Short, about 8 min
ADH and Oxytocin are (steroid/peptide/amine) hormones
Peptides
Which means that when they are synthesized, they start as preprohormones that then get cleaved into prohormones (in the ER) and then get converted to hormones (in the Golgi)
What do neurophysins (NP) do?
Bind to ADH or Oxytocin and prevent them from leaving the axon of the neuron before it’s ready to be released
Where do neurophysins (NP) come from?
They are released when the precursor hormone is cleaved into ADH or oxytocin
There are two kinds of neurophysins: NP-I and NP-II. Which one binds to ADH and which one binds to Oxytocin?
NP-I binds to oxytocin
NP-II binds to ADH
As the precursor hormone travels down the hypothalamic-hypophyseal tract (axon of the magnocellular neuron) it gets cleaved into these three things:
- ADH or Oxytocin
- Nurophysin (NP)
- A terminal glycoprotein
Central diabetes insipidus happens when there’s not enough ADH reaching the kidney. Why doesn’t the ADH reach the kidney?
The neurophysin (NP-II) that binds to ADH and keeps it from diffusing out of the axon prematurely is defective. ADH never reaches the circulation
What does oxytocin do to the uterus and the lactating breast?
Uterus: opens cervix and contracts uterus
Lactating breast: milk ejection
Suckling on a lactating breast (or hearing a baby cry or smelling a baby) will cause the release of what hormone?
Oxytocin
Which will then cause milk ejection from the nipple
Stretching of the cervix causes the release of what hormone ?
Oxytocin
Which then causes more uterus contraction
A POSITIVE FEEDBACK LOOP WHOAAAAAA 🙇♀️
What the F does oxytocin do in the heart?
The heart synthesizes and has receptors for OT.
When OT is released, it causes ANP/BNP to be released from the cardiomyocytes, and the ANP stimulates the release of nitric oxide from vascular endothelium.
Is there more oxytocin in the heart’s atria or ventricles?
3-4x more abundant in atria
What causes the release of OT from the heart?
Stretch (increased blood volume)
In what ways can Oxytocin regulate blood pressure?
- In peripheral arterioles, it induces nitric oxide release, causing vasodilation
- In cardiac muscle, it causes the synthesis and release of ANP and NO, causing negative inotropic and chronotropic effects. ANP induces vasodilation of peripheral arterioles.
- In the kidney, OT stimulates diuresis and natriuresis
- Decreases CRF which leads to decreased cortisol production= less stress hormone
What receptors does ANP bind to?
natriuretic peptide A Receptor (NPR-A)
What are the 2 sources of OT that the heart can respond to?
Pituitary
Cardiac
What effect does OT have on the heart?
Causes nitric oxide synthesis=dilation of coronary vessels
Slows heart rate
Decreases strength of contraction
Increase in glucose uptake
Why would we be interested in giving oxytocin to people with prediabetes?
Because OT increases glucose uptake by a GLUT4 mechanism, independent of the insulin pathway
What does this professor prefer to call ADH?
AVP
What is this professors name
I don’t know
Is this professor a serial killer
Probably
What causes the release of ADH?
Increase in plasma osmolarity
Decrease in blood volume
Angiotensin II
What effect will dehydration have on AVP/ADH release?
Increase
Dehydration causes hypovolemia and increase in osmolarity
Where are the osmoreceptors that detect changes in plasma osmolality?
In the anterior hypothalamus and outside the BBB
Which happens first: release of AVP/ADH or stimulation of thirst?
Release of AVP
What effect does AVP/ADH have on the kidney?
Causes water reabsorption from the distal tubule and collecting duct
Results in increased plasma volume and decrease in osmolarity
Low urine output
Does it take a small or large change in plasma osmolarity to stimulate release of AVP/ADH?
VERY SMALL CHANGE
This is a VERY sensitive system
A (large/small) change in blood volume will cause the release of ADH/AVP
VERY large blood volume decrease is required
8-10% of blood volume must be lost
What happens to GH levels as you age?
Decrease
When do GH levels peak?
Puberty
With the increase of GH release, the release of _________ also increases
IGF-1
What time of day does GH secretion peak?
During sleep
Is GH released in a steady stream?>
No, it is released in pulsatile bursts, so hormone levels fluctuate throughout the day, and plasma measurements are not a good reflection of the function of the anterior pituitary
Which hormones amplify the secretion of GH in men vs women
Men: testosterone
Women: estradiol (premenopausal women have more GH)
The pattern and frequency of pulse release is (the same/different) for males and females
The same
The principal regulators of GH release are:
1.
2.
- GH-releasing hormone
2. Somatostatin
Which cells release GH?
Somatotrophs
What are the target cells of GH-RH?
Somatotrophs
What kind of a receptor does GH-RH bind to on a somatotrophs?
Gα-s
Causes increase in cAMP
What kind of receptor does somatostatin bind to on somatotrophs?
Gα-i
Decrease in cAMP
What happens when GH-RH binds to a somatotroph
- Increased Adenylate cyclase activity
- Increased cAMP
- PKA is activated
- PKA phosphroylates CREB
- CREB causes the transcription of Pit-1
- Pit-1 activates the transcription of the GH gene, causing increased GH levels
- Pit-1 also upregulates the GH-RH receptor on the somatotroph
What happens when somatostatin binds to a somatotroph?
Adenylate Cyclase is inhibited
=no PKA to phosphorylation CREB, no Pit-1 transcription and no GH transcription
What things will stimulate GH release?
Hypoglycemia
Decreased FFAs
Arginine
Fasting/starvation/exercise
Stress
Sleep
Thyroid hormone
Androgens
Ghrelin
What things will inhibit GH release?
Hyperglycemia
Increased FFAs
Obesity
Aging
GH
IGF-1
How does arginine increase GH release?
It suppresses somatostatin release, allowing GH to be secreted unopposed
What are the 2 clinical methods of measuring GH status?
- Arginine
2. Insulin challenges to induce hypoglycemia
True or False:
GH has direct and indirect effects
True
The direct effects of GH are mostly __________
Metabolic
The indirect effects of GH are mostly ___________
Growth related
What 3 ways does GH affect metabolism?
- Protein anabolism (muscle)
- Lipolysis in adipose tissue to mobilize lipids for energy during fasting
- Stimulates hepatic gluconeogenesis (to provide fuel for the brain during fasting)
How could over secretion of GH lead to a form of diabetes?
Because it causes lipolysis in adipose tissue,and an increase of FFAs, muscle and adipocytes don’t uptake glucose
In addition, it stimulates gluconeogenesis by the liver.
Net effect is an increase in glucose and plasma insulin.
Because GH antagonizes the action of insulin, this can lead to a diabetogenic effect
**MUST KNOW THIS**
Why are GH’s effects on growth called “indirect”
Because GH causes the release of IGF-1 and IGFBP from the liver and IGF-1 is a peptide that actually acts on muscles, tissues, organs and chondrocytes to increase growth
IGF-1 is a peptide that should dissolve nicely in the plasma, yet 80% of it is bound to IGFBP! WHY
Becasue it increases the half-life of IGF1, which is important during times of growth
What are the effects of GH on growth?
These are actually indirect effects of GH since these are being done by IGF-1:
- Muscle- increase lean body mass via increased amino acid uptake and protein synthesis
- Tissues/organs- increased protein synthesis, DNA synthesis, cell size/number
- Chondrocytes- increase linear growth via increased amino acid uptake, protein synthesis, DNA synthesis, collagen, chondroitin sulfate, and cell size/number
Can GH-RH suppress its own release?
Yes
This is an ultrashort feedback loop!
How does GH have an ~autocrine~ inhibitory effect on the somatotroph?
GH feeds back to the hypothalamus to suppress GH-RH release
What effects does IGF-1 have on GH release
Suppresses GH release directly from the somatotrophs
Stimulates somatostatin production to inhibit the synthesis of GH
GH levels increase when:
Food is abundant and anabolic/growth states are favored
Or
Food is scarce and catabolic states are favored
BOTH!
However, the effects of GH are different
When protein and energy intake are ample, what happens to:
GH
IGF
Insulin
GH increases
IGF increases due to GH and insulin
Insulin increases due to the protein
When protein and energy intake are both ample, what happens to:
Protein synthesis
Growth
Caloric storage
Protein synthesis increases
Growth increases
No change in caloric storage
When carbohydrates alone are ingested, what happens to:
GH
IGF
Insulin
Protein synthesis
Growth
Caloric storage
GH decreases
IGF no change
Insulin increases
Protein synthesis no change
Growth no change
Caloric storage increased (due to insulin)
If you drink 2 L of sugary Cola what happens to your IGF levels
No change
In the fasted state, what happens to:
GH
IGF
Insulin
Protein synthesis
Growth
Caloric mobilization
GH increases
IGF DECREASES
Insulin decreases
Protein synthesis/growth DECREASE due to no IGF
Caloric mobilization increased (gluconeogenesis, lipolysis)
Why does IGF1 decrease in the fasted state even though the hypoglycemia increases GH release?
Fasting increases cortisol levels as well, so the GH and Cortisol promote the production of IGF-BPs.
The increase of IGF-BP in the plasma limits the bioavailability of IGF1 to the tissues, and growth is diverted
What is the difference between hypopituitarism and panhypopituitarism
Hypopituitarism: only GH is deficient
Panhypopituitarism: more than one anterior pituitary hormone is deficient
What is the most frequent cause of hypopituitarism?
Traumatic injury such as surgery, car accident, or ischemic damage
What is it called when there is ischemic damage to the mother’s anterior pituitary during the postpartum period?
Sheehan Syndrome
Can GH deficiency result from impairment at any site of the hypothalamus-pituitary-GH-IGF-axis?
Yes
What causes dwarfism?
GH deficiency before puberty
Why do some people affected by dwarfism appear pudgy?
Loss of GH-induced lipolysis
What causes Laron dwarfism?
Genetic defect in the GH receptor.
They have high GH levels but do not produce IGFs or IGF-BPs in response to GH.
Their hypothalamus-pituitary axis is totally fine, the defect is in the liver
What causes African pigmy-ism?
Partial resistance of GH-receptors in the liver leads to low levels of IGF during puberty
What causes acromegaly?
GH hypersecretion AFTER the epiphysis close in adults.
Usually caused by a tumor of the somatotrophs. IGF levels become very high.
What happens to patients who have acromegaly?
They have appositional bone growth and soft tissue deformities
Enlarged hands and feet, decreased fat content
Slow onset diabetes
Prognathism
Gynecomastia
Lactation
(Last two when prolactin and mammosomatotrophs are involved)
How is acromegaly treated?
Surgery to remove pituitary tumor
Octreotide (somatostatin analogues)
Dopamine analogues
GH-receptor antagonists if PRL is co-secreted
(He didn’t talk about the last two)
What causes gigantism?
GH oversecretion before puberty
What happens to people with gigantism
Excessive growth in long bones
Hyperinsulinemia/diabetes
Cardiac enlargement
