Hypothalamic-Pituitary relationships CIS Flashcards
Hypothalamus
what does it do?
what is physically connected to the hypothalamus?
important center in the brain that receives information from multiple centers
this releases hormones that are modulating the release of hormones from the anterior pituitary
also there are neurons within the hypothalamus that have fibers that project through the posterior pituitary.
Which pituitary is the pure endocrine gland?
Anterior Pituitary
another name for the anterior pituitary? Where is it coming from?
posterior?
adenohypophysis –> epithelial portion
neurohypophysis –> neural portion (because the fibers of the neurons are projecting to it)
What’s the connection between the hypothalamus and the pituitary gland? (2 names)
what’s within it? (2 things)
Hypophysial stalk (infundibulum)
within that is the median eminence and the portal system that is irrigating the anterior pituitary and bringing in releasing hormones from the hypothalamus
NOT THE POST.. that has a different system.
what is the optic chiasm and adenomas?
if certain cases of pituitary tumors (adenoma). if they’re big enough they can press into the optic chiasm and that, in some cases, are associated with loss of vision, headaches.
In the posterior pituitary, what are the two main cell populations that come from the hypothalamus and feed into it? what does each release usually?
we have the paraventricular nucleus (PVN) and the Supraoptic nucleus (SON).
these two cell populations are going to be secreting the posterior pituitary hormones..
ADH (from supraoptic nucleus)
Oxytocin (from paraventricular nucleus)
What does the anterior pituitary secrete?
collection of endocrine cells that each secrete different things except for one that secretes both FSH and LH
ACTH TSH FSH LH GH Prolactin
How is the anterior pituitary connected to the hypothalamus?
what happens from hypothalamus to ant pity from this?
what’s important to note about the concentration of hormones?
hypothalamic-hypophyseal portal vessels.
hypothalamus is releasing stimulating or inhibitory hormones that goes from there to the portal vessels of the hypothalamic-hypophyseal portal system to the anterior pituitary.
the hypothalamic hormones do NOT appear in the systemic circulation in high concentrations!.. they’re less detectable in the circulation!
what is a primary endocrine disorder?
low or high levels of hormone due to a defect in a PERIPHERAL ENDOCRINE GLAND (outside of the brain)
what is a secondary endocrine disorder?
low or high levels of hormone due to defect in the PITUITARY GLAND
what is a tertiary endocrine disorder?
low or high levels of hormones due to defect in the HYPOTHALAMUS
what is a tertiary endocrine disorder?
low or high levels of hormones due to defect in the HYPOTHALAMUS
What cell type releases:
ACTH?
TSH?
FSH/LH?
GH?
Prolactin?
Corticotroph
Thyrotroph
Gonadotroph
Somatotroph
Lactotroph/Mammotroph
What’s to note about the cell types and their presence in the anterior pituitary?
exception?
they are all grouped together with each other.. ACTH cells with ACTH cells regionalized, somatotropin with somatotroph, etc..
the only exception is the gonadotrophs.. those are dispersed throughout the ant pity
why are TSH,FSH, and LH part of a family?
they are all dimeric proteins!
you cut the pituitary stalk.. serum hormone levels are higher.. what serum hormone is it?
why?
Prolactin
hypothalamus inhibits prolactin with dopamine (PIF), so if we cut the communication to the anterior pituitary, we would expect that to be elevated.
prolactin is repressed for the most part unless childbirth.
Where is oxytocin released?
What if we cut the hypothalamus stalk?
posterior pituitary.
if we cut it, you’ll have a transient decrease
main stimulus of ADH?
would it go down?
if we cut the hypothalamus stalk, what would happen to ACTH and aldosterone?
you’d think the hypothalamus, but it’s actually the RAAS pathway
no
normal, no change in aldosterone! or ADH -> predominate RAAS pathway is doing it.
someone with amenorrhea, headaches, sweating, joint pains. massive growth in hands and feet and protrusion of lower jaw. sudden weakness.
what does she have?
Acromegaly –> Growth hormones are hyper secreted… and it’s NOT gigantism because she’s older and because it’s extremities (growth plates closed)!
acromegaly happens in a longer time frame.
classic signs of acromegaly?
protrusion of lower jaw
larger hands and feet
(rings no longer fit.. stuff like that)
Why is there a loss in the visual field with someone with acromegaly?
hyper secretion of growth hormones are due to a pituitary adenoma. so mass effect can impact the optic chiasm and give a headache and lose vision
what is IGF-1?
what about this an acromegaly?
what does IGF-1 do normally?
product that is stimulated by growth hormones on the liver!
IGF-1 regulates the growth hormones access.
product of binding growth hormones to the liver.. so we would expect it to be elevated in patients with hyper growth hormone secretions.
NORMALLY if IGF-1 is elevated then GH is decreased levels!
what is one of the effects of growth hormone??
diabetogenic.. it’s going to produce some insulin resistance. so we have an elevated levels of glucose!
looking at acromegaly, what tests are we going to look at?
IGF-1
glucose suppression tests
MRI (once we nailed down over secretion of growth hormone we want to see the source)
What are the notable somatic changes of acromegaly?
What can somatic changes lead to?
metabolic functions seen in acromegaly?
soft tissue growth, cartilage growth, organomegaly (hepatomegaly, cardiomegaly)
cardiomegaly can have people with hypertension –> these two lead to cardiovascular disease problems.
hyperglycemia
the actions of GH are mediated by what?
Somatomedins (IGF-1 + IGF-2)
GH stimulates somatomedin C(insulin like growth factor 1) gene transcription and secretion by the liver!
Insulin levels are impacted by excessive GH, but not relaying the information.
What is the regulation of growth hormone secretion
DRAW IT OUT
1) what does the hypothalamus release?
2) what does each of these things do?
3) what does the anterior pituitary release?
4) What happens when this gets to the target tissue?
hypothalamus releases GHRH –> stimulates the Anterior pituitary (somatotroph) –> release GH –> target tissue on the liver –> produces Somatomedins (IGF-1) –> negatively regulates Anterior pituitary release of GH.
GHRH (from the hypothalamus) inhibiting it’s own release too if there’s too much.
Somatomedin (release by target tissues) (IGF-1) can stimulate the hypothalamus to release Somatostatin (SRIF).. this INHIBITS anterior pituitary!
Growth hormone (released by the ant pity) can also regulate its secretion by stimulating Somatostatin
what are the 3 types of the pathophysiology of acromegaly?
Pituitary GH excess (Pituitary adenoma)
Extrapituitary GH excess –> coming from other tumors that are releasing GH (not in the pituitary
GHRH excess (through a tumor in carcinoid tissue)
What is an explanation of amenorrhea? (3 ways)
Gonadotrophs are decreased.
prolactin effects the release of gonatropins.. this effects their menstrual cycle.in men it’ll be loss of libido.
could be a mass that’s affecting the gonadotrophs since they’re dispersed and not localized.
for acromegaly, why is IGF-1 measured initially? why not measure GH?
growth hormone release is pulsatile. so during the whole 24 hour cycle we have peaks of GH being released.
IGF-1 doesn’t vary as much as GH does throughout the day. it’s an integrative response to GH. and it’s the product of GH
for acromegaly, what dynamic test do we do and how does it work?
oral glucose tolerance test.
the patient will ingest 75g of glucose and you’re measuring GH.
high glucose level will usually shut down growth hormone secretion in normal. but in acromegaly there is a lack of shutting down that GH release.
What drugs are you going to use for acromegaly? (the basis, not specific ones)
3 types
somatostatin agonist (lowers it!)
GH antagonist. (lowers it too!)
Dopamine receptor agonists (may release GH secretion)
How is growth hormone secreted in somatotrophs? when is it mostly secreted?
PULSATILE MANNER… it’s mostly secreted during the night
What is GH excess before puberty called?
what does GH act on to cause bone growth on the epiphyseal plate or on jaw bones or stuff like that?
Gigantism because the epiphyseal plates are not closed!
GH acts on Chondrocytes, which cause bone growth.
What is the diabetogenic effect for the growth hormone metabolic function?
what does it cause?
what is the overall end goal?
(increasing blood glucose concentration)
–> causes insulin resistance
–> lowers glucose uptake and utilization by target tissues
–> increase lipolysis in adipose tissues
result: increase blood insulin levels
What is the effect of protein synthesis and organ growth for growth hormone?
what mediates this?
Increase uptake of amino acids
Stimulates synthesis of DNA, RNA, and protein
This effect is mediated by somatomedin (IGF-1)
Fasting causes what for GH, IGF-1, and Insulin levels?
In fasting… somatomedin and insulin are depressed… that somatomedin that is depressed contributes to the increase in GH!
since somatomedin are also mediating protein synthesis and growth.. we’ll also see lower of these
insulin also has lowers protein synthesis and growth.
so less negative feedback on GH (so higher production!)
galactorrhea?
production of milk
girl has milky substance from breasts.. presents with amenorrhea…
what is elevated?
why is it amenorrhea causing??
prolactin.
prolactin negatively regulates Gonadotrophs.
high prolactin levels impact the access of gonadotropin by (GnRH)..
Other than prolactin levels, how would you know that someone has amenorrhea?
FSH or LH levels are depressed.
Prolactin does what to the hypothalamus?
how does this affect the ovaries?
inhibits the release of GnRH from the hypothalamus to the anterior pituitary..
this will decrease FSH and LH which targets the ovaries.
What does Dopamine do to the anterior pituitary and prolactin/FSH/LH?
what does GnRH do to the anterior pituitary (from the hypothalamus)
negatively regulates the anterior pituitary and negatively inhibits Prolactin and FSH/LH
increases the release of FSH, LH
What are the 3 different types of pituitary Adenomas?
Prolactinoma
Acromegaly
Cushing’s Disease
What is Cushing’s disease?
(pituitary adenoma) hyper secretion of ACTH from corticotrophs.
so you’ll see more cortisol and sex androgen
What happens in a non-functioning adenoma?
secretes FSH and LH but considered nonfunctioning
If we have damaged pituitary failure, we can have decreased levels of hormones.
ACTH cells affected?
FSH/LH
GH?
ADH
low cortisol –> loss of pigmentation
hypogonadism
short stature in children. adult? no effect.
diabetes insipidus
Sheehan’s syndrome?
pituitary in pregnancy is enlarged and more vulnerable to infarction. (associated with hemorrhage during labor)
postpartum hypopituitarism due to necrosis of the pituitary gland.
most patients come with agalactorrhea and or difficulties in lactation, amenorrhea, hypothyroidism
woman has necrosis of posterior pituitary.. what’s going to present (excluding RAAS system?)?
Hypernatremia.
you don’t have ADH… so super high levels of sodium. so that’s hypernatremia.
oxytocin and ADH secretion?
Prepro-oxyphysin formed in the cell body of neurons –> Pro-oxyphysin (via cleavage of signal peptides and packaging in vesicles
then prooxyphysin is cleaved again releasing Oxytocin and NP1
the ADH is similar:
Prepropressophysin –> Propressophysin –> ADH and NPII
Triggers of ADH secretion (3)?
what are the three types of receptors for ADH secretion?
What is the neuron that sends it to the hypothalamus?
decreasing blood pressure, decrease in arterial stretch due to low blood volume, increase in osmolarity.
cardiac/aortic receptors, atrial stretch receptors, hypothalamic osmoreceptors
Sensory neuron, sensory neuron, INTERNEURON
leads to the hypothalamic neurons to synthesize ADH
Actions of ADH?
kidneys or blood vessels
end goal of kidneys = (V2 receptors) increase reabsorption of water by increasing aquaporin receptors.
end goal of vessel = v1 leads to vasoconstriction
both end goal = lead to increase blood pressure and increase blood volume.
Angiotensin 2 does what for ADH?
increase in angiotensin 2 increases secretion of ADH
how does ADH work on the distal tubule?
in the distal tubule, binding ADH onto B2 receptor in the principle cell, triggering the cascade to increase cAMP and protein kinase A, triggering the insertion of Aquaporin 2 onto the membrane.
when we have dehydration (hyperosmolarity), what happens?
too little water in the system.
hypothalamus detects too little water… pituitary gland increases ADH release
kidneys remove less water from the blood so less water is lost in the urine. urine is more concentrated!
when we have hypoosmolarity/hypervolemia what happens?
decreases the amount of ADH so the urine is more dilute.
we want the body to decrease the ADH.
osmolarity is significant for ADH secretion, but sometimes volume is more important.. How?
ADH regulation is heavily influenced by the volume. in a case of hypovolemia (low volume such a a hemorrhage), ADH secretion is going to go super fast even when the osmolarity is kept within the normal range.
if we have a volume expansion through hypervolemia.. this is enough to lower the increase of ADH secretion regardless of the osmolarity.
A lot of water being lost, what disease is it?
diabetes insipidus (central or nephrogenic)
Water deprivation test?
what happens if you administer vasopressin and it concentrates urine?
what if it doesn’t respond to vasopressin?
after the water deprivation, we see no response. the osmolarity of the urine is still pretty diluted..
after that test we give them vasopressin (ADH), it starts concentrating that urine.
this would be central diabetes insipidus (lack of ADH)
nephrogenic (it doesn’t respond to vasopressin)
What inhibits the release of prolactin?
what activates release of prolactin?
what predominates?
PIF (dopamine)
TRH
PIF inhibition release
What are the two GH hormones that are important for regulation?
which predominates?
GHRH (Positively regulates)
Somatostatin (negatively)
both!!
If we have elevated concentration of IGF-1, what do we expect of GH?
DECREASED
the hormone output of the peripheral organs can impact the hypothalamic pituitary axis
What does growth hormone have on linear growth?
what mediates it?
stimulates synthesis of DNA, RNA, protein
increase metabolism in cartilage-forming cells and chondrocyte proliferation
IFG-1
Why are nonfunctioning adenomas typically associated with FSH and LH?
what’s being oversecreted is a particular subunit, alpha subunit of LH or a beta subunit of FSH and so on. so it’s less likely to be functional! whatever is functional, they aren’t pushing enough out.
What are the causes of Central DI vs Nephrogenic DI?
what levels of ADH are in each and what is the cause?
if you give desmopressin?
Central: Lack of ADH resulting from the damage to the pituitary… destruction of the hypothalamus..
LOW ADH
you know it’s this because the body responds to desmopressin
Nephrogenic: Kidneys are unable to respond to ADH.
its caused by lithium drugs, or chronic disorders.
Desmopressin doesn’t do shit
HIGH ADH
What is SIADH and how does it work?
excessive secretion of ADH
Excessive water retention
Hypoosmolarity fails to inhibit ADH release… so even though you drink a ton of water, ADH does NOT stop.
