M1 L3 Flashcards
1
Q
Whats the hypothalamus pituitary axes?
A
The HPA axis plays a vital role in maintaining homeostasis, regulating energy levels, and responding to stress.
2
Q
hormones that end in RH come from where? What does RH mean
A
the hypothalamus
RH means releasing hormones
3
Q
Which hormones are tropic hormones?
A
Hormones that come from the pituitary.
4
Q
What is CRH
A
corticotropin releasing hormone
5
Q
What is GHRH/SMS
A
Growth hormone RH & GHIH (growth hormone inhibiting hormone) = somatostatin
6
Q
What is dopamine?
A
prolactin inhibiting hormone
7
Q
Whats TRH
A
thyrotropin RH
8
Q
Whats GnRH
A
gonadotropin releasing hormone
9
Q
Whats ACTH
A
Adreno-corticotropic hormone
10
Q
Whats GH
A
growth hormone
11
Q
whats PRL
A
prolactin (milk production)
12
Q
Whats TSH
A
thyroid stimulating H
13
Q
whats FSH
A
follicle stimulating H
14
Q
Whats LH
A
luteinizing H
15
Q
Role of posterior and anterior pituitary?
A
Anterior: Produces and secretes several hormones that regulate other endocrine glands and body functions.
Posterior: Stores and releases hormones made by the hypothalamus.
16
Q
what are the hypothalamic nuclei
A
The hypothalamic nuclei are clusters of neurons in the hypothalamus, each with specific functions
things such as: reproduction, body temperature, food intake + regulating emotions and motivated behaviors
17
Q
What are the 3 three main ways the hypothalamus communicates with the rest of the body and brain?
A
1) Hormonal (endocrine) control of the pituitary gland (via blood and nerves)
2) Neural communication with the rest of the brain + CNS
3) Direct communication with circulation via leaky blood brain barrier (BBB)
18
Q
How does the hypothalamus link the nervous system to the endocrine system?
* how does it communicate to it?
A
The hypothalamic neurohormones will synthesize and secrete neurohormones to stimulate or inhibit the secretion of pituitary hormones.
The Anterior pituitary is communicated with via the hypophyseal portal system
The Posterior pituitary is communicated with via direct innervation
19
Q
How does the hypothalamus communicate with the rest of the CNS?
- associated w which ventricle
A
Does this via projections all over the CNS. * hypothalamic nuclei are closely associated with third ventricle
20
Q
How does the hypothalamus do direct communication with circulation?
A
Does this via leaky blood brain barrier (BBB)
- Some parts of the hypothalamus have a leaky blood-brain barrier (BBB). Helps in monitoring and responding to changes in the body’s internal environment.
21
Q
What is neurosecretion? What are neurohormones?
A
neurons make, store, and secrete hormones. (stored to be ready for use)
neurohormones are hormones made by the brain (CNS)
22
Q
in the neurosecretion steps, what leads to action potentials at the axon terminal
A
Synaptic and hormonal excitation of the neurosecretory cell body
- stimulation of cell leads to firing - so firing is
23
Q
Whats stimulus secretion coupling?
A
the process by which a cell senses a stimulus and then responds by releasing a substance
Stimulus → triggers cell response → leads to secretion
24
Q
What is the amount of neurohormone secreted proportional to?
A
The amount of neurohormone secreted is proportional to the frequency of the action potentials.
- more AP more hormone secretion
25
In the neurosecretion steps, what does depolarization trigger?
increase in intracellular calcium.
26
What happens once there is an increase in intracellular calcium for neurosecretion?
vesicles full of neurotransmitters fuse with the plasma membrane and release (exocytosis) their granule contents into the synapse — that’s how neurons communicate!
27
Where do neurons of the hypothalamus secrete hormones?
at the primary plexus in the median eminence (ME)
28
Once hormones are in the median eminence where do they go?
From there, the blood (carrying the hormones) flows down through hypophyseal portal veins into the anterior pituitary. In the anterior pituitary, there’s a secondary capillary plexus where these hormones act on pituitary cells.
29
Once the hormones are in the anterior pituitary what happens?
Once the hormones reach the anterior pituitary, they bind to specific target cells called trophic cells. These trophic cells respond by releasing trophic hormones into the bloodstream, which then act on peripheral endocrine glands.
Ex: gonadotrophes will release LH and FSH which then stimulates ovaries/testes
30
How does one releasing hormone (GnRH) regulate two gonadotropins?
It is released in pulses - so the different frequencies will favor either LH or FSH production.
31
Which pulse stimulates LH vs FSH?
* Fast (> 1 pulse / h) favors LH
* Slow (< 1 pulse per 2-3 h) favors FSH
32
What happens if you do a release of continuous GnRH?
It will completely suppress LH/FSH secretion
* no pulse - they're inhibited
* also due to desensitization
33
Whats pulsatile secretion?
The timing and frequency of those GnRH pulses control how much LH or FSH is released.
34
Why is it important that the hypothalamus and anterior pituitary are physically close to each other?
Because GnRH has a short half-life, the short distance ensures it reaches the pituitary quickly and effectively.
35
What is the half-life of GnRH and why does it matter?
GnRH has a short half-life (a few minutes), so it must be released locally and in pulses to act before it's broken down.
36
What does GnRH do to begin the triggering of LH and FSH release in the pituitary?
GnRH binds to its GPCR (GnRH receptor) on gonadotrope cells, activating signaling pathways that lead to LH and FSH secretion
37
What are Neurosecretory magnocellular neurons?
* where located
* what make
These are large neurons located in the supraoptic nucleus (SON) and paraventricular nucleus (PVH) of the hypothalamus.
They synthesize hormones like oxytocin and vasopressin (ADH).
38
What are the herring bodies?
swellings along the axon where hormones are stored temporarily
39
What are Neurovascular junctions?
* why release hormones?
Sites in the posterior pituitary where hormones are released into the blood.
release is in response to action potentials and pituicytes
40
What are Pituicytes
Glial-like support cells that help with hormone storage and release.
41
Hormones of the posterior Pituitary: Vasopressin
* what do
* Retains water by translocating aquaporins to the collecting ducts & distal convoluted tubule
membranes in the kidney
* Regulates peripheral resistance on vascular smooth muscle
(inc arterial pressure)
42
Hormones of the posterior Pituitary: Oxytocin
* what do
*Stimulates smooth muscle in the uterus during birth
*Maintains vas deferens & participates in orgasm/
ejaculatory reflex
* Stimulates smooth muscle in secretory alveoli of the mammary gland: milk ejection
43
What regulates neuropeptide hormone production
transcription and translation
44
Hypothalamus receives projections to & from:
* Other limbic regions
* Other parts of the cortex
* Brainstem
45
What is Grey haze:
* what does it confirm
infiltration of a dye that does not cross tight junctions
You can see grey in the hypothalamic area called ARH (arcuate nucleus of the hypothalamus)
-> The hypothalamus has a leaky brain-CSF barrier.
46
What allows for diffusion of substances into or from the CSF
Leaky barrier between the hypothalamus and CSF
47
How does the leakiness of the blood-brain and brain-CSF barriers affect communication of steroid vs protein hormones?
Steroids: already lipophilic - they easily diffuse across the BBB and brain-CSF barrier.
* Barrier leakiness isn’t a major limitation for steroids — they’re naturally built to cross.
Protein hormones: Hydrophilic & large - They do not easily cross the BBB or brain-CSF barrier.
* Need specific transporters, receptors, or access through leaky regions
48
What does hydrophilic mean and why is it bad in the membrane context?
Dissolves easily in water or interacts well with it
Doesn’t mix well with fats or lipids, so it can’t cross cell membranes easily (because membranes are made of lipid layers).
49
what are circumventricular organs?
* ex?
special group of brain structures where the blood-brain barrier (BBB) is naturally leaky and is intentionally less restrictive.
ex: median eminence
50
What is the median eminence (ME)?
A hypothalamic structure that links the brain to the pituitary gland, allowing hormone release into the bloodstream to control the pituitary
51
What happens at the median eminence?
the hypothalamus communicates with the circulation via a leaky blood-brain barrier, allowing hypothalamic neurohormones to enter the portal bloodstream and reach the anterior pituitary.
* The median eminence is the site where hypothalamic neurohormones (like CRH, GnRH, TRH, GHRH, dopamine) are released into the hypophyseal portal blood vessels. Without it, these hormones cannot reach the anterior pituitary effectively.
52
What are fenestrations
these are little holes/windows in capillaries in the ME that allows peptides, proteins, and other blood-borne molecules to pass through more easily
53
Galactorrhea
relieving dopamine suppression of lactation outside of breastfeeding
* basically u start letting milk out even tho u aren't pregnant
54
Explain the negative feedback that happens in the menstrual cycle
* Rising estradiol suppresses FSH/LH
* Dropping estradiol leads to elevations in FSH/LH
cycles between these
55
What do kisspeptin neurons do?
These neurons sense estrogen and progesterone levels because they have estrogen receptors.
They release kisspeptin, a small peptide signal. Kisspeptin neurons stimulate GnRH neurons.
* located in hypothalamus
56
How do GnRH neurons contribute to negative feedback?
* name of their receptor and its action
* How does kisspeptin get turned off?
These neurons do not have estrogen receptors, so they can’t “see” steroid hormone levels directly.
Instead, they receive input from kisspeptin neurons. They have GPR54 receptors, which bind kisspeptin.
* When activated, they release GnRH into the hypophyseal portal system.
ALSO GnRH is only turned off when Kisspeptin gets turned off (bc kisspeptin only stimulates her). High estradiol or testosterone → inhibits kisspeptin neurons (in the arcuate nucleus)
57
What is the receptor GnRH neurons express for kisspeptin
GPR54
58
What do the two populations of kisspeptin neurons mediate?
one that mediates negative feedback and one that mediates positive feedback
59
Explain this negative feedback flow
1) Kisspeptin neurons release kisspeptin
2) GnRH neurons receive kisspeptin via GPR54 receptors
3) GnRH neurons release GnRH which goes through the hypophyseal portal vessels and travels to the anterior pituitary
4) GnRH stimulates the pituitary to release LH and FSH who enter the bloodstream
5) Ovaries respond to LH & FSH and then ovaries produce estradiol and progesterone
6) Estradiol/Progesterone go back to the brain and inhibit kisspeptin neurons.
60
What happens when kisspeptin neurons get inhibited by estradiol and progesterone:
Estradiol & progesterone (from the ovary)
⬇
Inhibit kisspeptin neurons (which DO have estrogen receptors)
⬇
Less kisspeptin
⬇
Less GnRH from the hypothalamus
⬇
Less LH & FSH from the pituitary
⬇
Less stimulation of the ovaries
61
What are kisspeptin neurons inhibited by?
* in which part of hypothalamus?
Are inhibited by high estrogen/progesterone (for neg feedback)
Ovaries respond to LH/FSH by producing estradiol and progesterone, which go back and inhibit the kisspeptin neurons
Estradiol from the ovaries acts on Kisspeptin neurons in the ARC to cause negative feedback
62
Kisspeptin found in Arcuate nucleus (ARH)
* what do?
Mediates negative feedback from estrogen/progesterone
63
Kisspeptin found in Anteroventral periventricular nucleus (AVPV) aka Rostral Periventricular Region of the 3rd Ventricle (RP3V)
* what do?
Mediates positive feedback
* Just before ovulation, estradiol levels rise high and stay elevated for ~36 hours.
* This high, sustained estradiol level actually stimulates AVPV/RP3V kisspeptin neurons via ERα receptors.
* They release a surge of kisspeptin → which massively stimulates GnRH neurons → GnRH surge → LH surge → ovulation!
64
What is kisspeptin regulated by
Kisspeptin neurons have estrogen receptors, so they’re regulated by circulating estrogen levels.
* High or low estrogen will affect how much kisspeptin they produce — this is how feedback loops are possible.
65
What gene are kisspeptin neurons encoded by
the KISS1 gene
66
What kind of receptor is the GRP54 receptor found on GnRH neurons
GPR54 is a G-protein coupled receptor
* GPCRs trigger intracellular signaling when activated.
* So kisspeptin binding to GPR54 activates intracellular pathways in GnRH neurons → leads to GnRH release.
67
Explain the positive feedback that happens in the menstrual cycle
There is an LH surge AFTER a surge in estradiol (prolonged estradiol causes it)
The pos feedback:
* rising estradiol and LH together
* Negative feedback suspended
68
Explain this positive feedback loop:
1) Kisspeptin responds to rising estradiol levels and stimulate GnRH release
2) GnRH Neurons release GnRH in response to kisspeptin input and reach anterior pituitary via portal
3) pituitary receives GnRH and responds by releasing LH (Luteinizing Hormone) and FSH (Follicle Stimulating Hormone).
4) These act on the ovary, stimulating follicle development and more estradiol production — which loops back positively.
69
How does the HPG switch from negative to positive feedback?
estradiol levels rising above a threshold flips the switch from negative feedback to positive feedback.
The HPG axis uses negative feedback when estradiol is low to moderate to prevent overstimulation, but switches to positive feedback when estradiol is sustained at high levels, triggering kisspeptin activation, a GnRH surge, and ovulation.
70
What happens to Kiss1 expression in the AVPV when estradiol is high?
Kiss1 expression goes up → stimulates GnRH → positive feedback.
* AVPV responsible for positive feedback
71
What happens to Kiss1 expression in the ARC when estradiol is high?
Kiss1 expression goes down → suppresses GnRH → negative feedback.
* ARH responsible for negative feedback
72
What is the effect of removing ovaries (↓ estradiol) on Kiss1 in the AVPV?
Kiss1 goes down → less GnRH release.
With no ovaries, estradiol drops. AVPV neurons need high E2 to be active, so without it, they shut down → Kiss1 expression drops → less GnRH → no LH surge = no ovulation.
73
What is the effect of removing ovaries on Kiss1 in the ARC?
Kiss1 goes up → more GnRH release.
* bc she maintains neg feedback and kiss1 is low - she needs to bring it back up
74
What does kisspeptin do to GnRH neurons?
It stimulates depolarization → triggers GnRH release.
75
What’s So Special About Prolonged Estradiol Exposure?
Sustained high estradiol (≥ ~48 hours) is what flips the HPG axis from negative to positive feedback
Builds up kisspeptin activation in the AVPV and Increases GnRH receptor expression in the pituitary
76
How does estrogen (estradiol) affects neurons in the brain to trigger the LH
- The prolonged expression of estradiol induces expression of progesterone receptors (PR) in AVPV kisspeptin neurons. This amplifies kisspeptin release and makes GnRH stronger which leads to LH surge
77
What is the negative feedback loop maintained by in men?
Negative feedback mediated by androgen receptors and estrogen receptors on kisspeptin neurons
78
What 2 hormones regulate lactation?
Dopamine and oxytocin
79
What do dopamine neurons in the ARC do?
Dopamine neurons in the ARC release dopamine into the anterior pituitary through the hypophyseal portal system.
● Binds to D2 receptors in lactotrophs of the AP
● This inhibits the release of prolactin through tonic inhibition (bc we make the dopamine all the time) → no milk production
80
What do oxytocin neurons in the ARC do?
Oxytocin neurons in the posterior pituitary promote milk let down once its already produced
● It’s release from the posterior pituitary allows for lactation
● Oxytocin release is driven by cues from babies
81
What do the lactotropes do?
Produce prolactin which produces milk. but only oxytocin can cause letdown of milk
82
What is galactorrhea
Galactorrhea is the unexpected or inappropriate production of breast milk, in someone who isn’t pregnant or breastfeeding.
83
How can antipsychotic medications cause galactorrhea through their effect on dopamine and prolactin?
Dopamine neurons in the hypothalamus normally inhibit prolactin (PRL) release from the anterior pituitary.
Many antipsychotics are D2 receptor blockers. They block dopamine’s inhibitory signal.
INHIBIT THE INHIBITOR --> spontaneous lactation
84
What other other ways galactorrhea can occur?
Brain tumor or car accidents
Tumor can block communication from the hypothalamus and pituitary - no D2 getting into the anterior pituitary to block prolactin
85
Predict how circulating hormone levels change as a result of positive feedback
high E2 from ovaries leads to neuroprogesterone production in the hypothalamus and activates Kiss1 neurons who stimulate GnRH which leads to inc LH
in short - High estrogen flips the system into positive feedback, causing a chain reaction that leads to a surge in LH and eventually ovulation.
86
Explain clinical implications of GnRH agonists and antipsychotic medications with respect to neuroendocrine regulation
– GnRH agonists exploit the need for pulsatile stimulation, tonically inhibit the HPG axis
– DA neurons tonically inhibit lactotrophs, interference with this inhibition (via antipsychotics, tumor, accident) can lead to galactorrhea
87
GnRH agonists [BLANK ] the production of LH/FSH because they provide [BLANK ] GnRH stimulation instead of [BLANK] GnRH stimulation.
GnRH agonists [decrease ] the production of LH/FSH because they provide [continuous ] GnRH stimulation instead of [pulsatile ] GnRH stimulation.
88
Does this correspond more closely with hypothalamic neurons that communicate with the anterior pituitary or the posterior pituitary:
* The neurons have axons that terminate in the primary plexus of the median eminence
anterior pituitary
89
Does this correspond more closely with hypothalamic neurons that communicate with the anterior pituitary or the posterior pituitary:
* The neurons of the hypothalamus secrete hormones into the general circulation
posterior pituitary
90
Does this correspond more closely with hypothalamic neurons that communicate with the anterior pituitary or the posterior pituitary:
The neurons of the hypothalamus secrete hormones into the hypophysial portal vessels
anterior pituitary
91
Neurons of the hypothalamus secrete a hormone that stimulates the secretion of another hormone by the pituitary
anterior pituitary
92
The neurons make the hormone but the release is also regulated by the pituitary
posterior pituitary
93
The leaky [BLANK ] barrier allows for diffusion of substances from the circulation to the hypothalamus. This allows the hypothalamus to communicate with [BLANK].
The leaky [blood-brain ] barrier allows for diffusion of substances from the circulation to the hypothalamus. This allows the hypothalamus to communicate with [the rest of the body ].
94
The leaky [BLANK ] barrier allows for diffusion of substances from the cerebrospinal fluid to the hypothalamus. This allows the hypothalamus to communicate with [BLANK ].
The leaky [brain-CSF ] barrier allows for diffusion of substances from the cerebrospinal fluid to the hypothalamus. This allows the hypothalamus to communicate with [the rest of the brain ].
95
Kisspeptin neurons in the AVPV/RP3V and Kisspeptin neurons in the Arc respond differently to which hormone?
They respond differently to estradiol.
96
If you were to stimulate Kisspeptin neurons in the AVPV/RP3V of intact mice, which hormone would they release?
Stimulating kisspeptin neurons of intact mice causes a release of kisspeptin which then stimulates the release of GnRh. This makes the overall effect of stimulation is the release of GnRH. This happens through depolarization.
97
How does Kisspeptin treatment affect GnRH neuronal activity?
Kisspeptin stimulates the depolarization of GnRH neurons because they express the receptor for kisspeptin (which is GPR54).
98
Which population of neurons would you hypothesize is present only in females?
The kisspeptin neurons in the AVPV/RP3V are involved in the positive feedback and LH surge and this is something specific to female reproduction. So I would say these neurons are only present in females since they are related to this type of surge and feedback loop. Males also do not experience positive feedback loops so this is more evidence of it being present in females.
99
What are trophic cells?
Examples?
specialized cells in the anterior pituitary that respond to signals from the brain and release hormones into the bloodstream.
Ex: gonadotrophes, corticotrophs, somatotrophes
100
What are Peripheral Endocrine Glands?
Examples?
the glands outside the brain that respond to the hormones from the anterior pituitary
Ex: thyroid gland, adrenal gland, ovaries/testes (gonads)
101
Tropic hormone examples
LH, FSH, TSH, ACTH etc
