Endocrine Lecture 2 Flashcards
Hypothalamus regions receive unique inputs from all areas in the body and then the hypothalamus has to integrate those signals into a singular output:
either to the anterior or posterior pituitary
What hormones are released from anterior vs posterior pituitary?
Anterior Pituitary: ACTH, GH. TSH, LH, FSH, Prl (metabolism, growth and development, reproduction, lactation and response to stress)
Posterior Pituitary: OT and AVP (water balance, parturition and lactation)
The hypothalamus is an example of a _____ endocrine gland.
It is ______ and dumps its hormones _____
Hypothalamus is a classic endocrine gland
It is ductless, dumps its hormones into the blood stream at the medial geniculate
Explain the functions of these hypothalamuc nuclei:
PVN
POA
SO
AR
Hypothalamic Nuclei Functions:
PVN (avp neurons, regulates thirst, blood pressure, also mood/emotion/stress)
POA: reproductive function and body temp
SO (lots of avp neurons regulating osmolarity)
ARC (regulates stress and feeding behavior)
What is the median eminence?
The median eminence is the floor of the hypothalamus, convergence point for axons
“Important to point out that cell bodies of neurons are located in the hypothalamic nuclei, BUT their axons are extended down to the median eminence, where hormones are dumped directly into the blood”
Explain the following hypothalamic releasing factor hormones (which brain nucleui do they originate from, what is their pituitary target, function)
- GnRH and GnIH
- CRH
- TRH
- GnRH (IH is inhibitor) comes from neurons scattered all over brain, but majority in POA, targets gonadotrope cells in the pituitary to release FSH and LH for reproductive function
- CRH comes from the PVN to target corticotropes in the pituitary to release ACTH for many functions (glucocorticoids)
- TRH comes from the PVN, and targets thyrotropes in the pituitary to release TSH for function of thyroid hormone (also has many functions)
Explain the following hypothalamic releasing factors (which nuclei they originate from, what their pituitary targets are and what their function is)
- GHRH
- Somatostatin
- Dopamine
- GHRH comes from the Arcuate nucleus to target somatotropes in the pituitary to release GH, function of growth and development
- Somatostatin (GHRH inhibitor) comes from the PeVN to target somatotropes in the pituitary to inhibit GH as its function
- Dopamine: comes from arcuate nucleus, targets lactotropes in the pituitary to release prolactin for milk production
GnRH:
Cell bodies are _________
Very long axons extend toward the _______
If you do not have these neurons you will be _____
GnRH is a _______ hormone, meaning that it binds to a ____-
GnRH:
Cell bodies are scattered throughout forebrain, with the largest concentration in the POA (Pre-optic area)
Very long axons extend toward the median eminance
If you don’t have these neurons you will be sterile
GnRH is a decapeptide, meaning its a peptide hormone and therefore binds to a cell surface receptor
Kallman Syndrome:
What is kallman syndrome?
Kallman Syndrome:
Rare genetic disease where the GnRH neurons fail to enter the CNS during embryonic development (these neurons originate in the nose and travel to the brain during early development)
Kallman disease is characterized by reproductive failure and anosmia
It is heritable: X linked (Kal 1) and Autosomal (Kal 2)
GnRH:
GnRH is released via the ___________ system and binds to cell surface receptors on ________ (pituitary cells).
It then through different secondary messenger systems causes the pituitary to release two hormones: ____, ___
Explain how one hormone can regulate the synthesis of two different hormones
GnRH:
GnRH is released via the hypophysial portal system and binds to cell surface receptors on gonadotroph cells in the pituitary. It then causes through different pathways those gonadotroph cells to release LH or FSH
It regulates two totally different hormones from the same cell type by regulating the frequency by which GnRH itself is released / “pulsitility” (LH is fast pulsitility, FSH is slow pulses), and also by two different signaling pathways.
Explain the hypophysial portal system
Can you measure hypothalamuc releasing hormones via a blood test?
The hypophysial portal system is a vascular connection between the hypothalamus and the pituitary gland.
The cell bodies of the hypothalamic releasing and inhibiting hormones are within the hypothalamus, and the axons of them end right at the median eminence, where the hormones travel through portal vein to get to anterior pituitary.
NOTE: you CANNOT measure these hypothalamic releasing portal veins in systemic blood, only in portal vein so they are never looked at
GnRH Pulsitility:
Explain the relationship between GnRH pulsing and the pituitary hormone pulses of LH and FSH
Also explain the significance of GnRH pulsing and why it is important that it is pulsitle
GnRH Pulsitility:
- GnRH pulse is right before the pituitary hormone pulse
- Pulse frequency determines which pituitary hormone is released:
- Slow: FSH
- Fast: LH
For GnRH pulsitility is important to recycle receptors back to the surface AND important for distinguishing which pituitary hormone gets released
Explain the difference for pituitary hormones between the Beta subunit and the alpha subunit in all the hormones
All pituitary hormones contain ghe same alpha subunit (a-GSU)
But they all differ in which Beta subunit they have
Explain the tuberoinfundibular system vs the neurohypophysial tract
Two Major Pathways for Hypothalamic-Pituitary Connection:
- Tuberoinfundibular system: comprises all neurons that send axonal projections to the median eminence. Hormones target the anterior pituitary through the portal vein
- Neurohypophysial Tract: comprises neurons whose axons terminate in the posterior pituitary
Pituitary Gross Anatomy:
The Anterior Pituitary main part is called the _____
The posterior pituitary consists of ______ and ____
Pituitary Gross Anatomy:
Anterior Pituitary: pars distalis
Posterior Pituitary: pars nervosa and infundibulum (stalk)
Explain the different tissue types that make up the anterior and posterior pituitary:
Anterior pituitary: _______ tissue
Posterior pituitary: ______ tissue
Anterior pituitary: glandular tissue: cords of epithelial cells
anterior pituitary: adenohypophysis
Posterior Pituitary: neurohypophysis, neural tissue
Label these stains: which part is anterior pituitary which part is posterior pituitary
Darker stain: anterior pituitary (pars distalis)
Lighter stain on the bottom: posterior pituitary (pars nervosa)
Posterior Pituitary - Neurohypophysis:
Axons from ______ neurons terminate in the neurohyphophysis
Blood supply is seperate, and is from the ____ artery
Major hormones released from posterior pituitary:
- *
Posterior Pituitary: Neurohypophysis:
Axons from magnocellular neurons terminate in neurhypophysis (neurohypophysial tract)
Blood supply from inferior hypophysial artery- has its own capillary bed
Major Hormones: Argininge Vasopressin (AVP) and oxytocin (OXY)
Posterior Pituitary:
Pars Nervosa Histology:
Axons terminate near the _________
Posterior Pituitary:
Axons terminate near fenestrated capillaries that way they can go right into the blood stream
Posterior Pituitary: Pars Nervosa and Herring Bodies;
What are herring bodies?
Pars Nervosa:
Herring bodies are dilations of unmyelinated axons near their terminals
Contain vesicles of either AVP or oxytocin plus a binding protein called neurophysin (the copeptide)
Anterior Pituitary- Adenohypophysis:;
The median eminence (ME) is the interface for all hypophysial hormones
ME lies _____ the BBB and forms the floor of the third ventricle (explain what that means)
Anterior Pituitary - Adenohypohysis:
The median eminence (ME) is the interface for all hypophysial hormones
ME lies outside the BBB and forms the floor of the third ventricle
This means that hormones can also be regulated from things outside of the blood stream
**Explain which cells within the anterior pituitary are responsible for producing the following hormones:
LH/FSH
TSH
ACTH
GH
Prolactin
LH and FSH : gonadotrophs
TSH: thyrotrophs
ACTH: corticotrophs
GH: somatotrophs
Prolactin: lactotrophs
Anterior Pituitary Cell Types and Hormones:
_______ are the most abundant hormone producing cell type (include which two types of cells)
Basophils - dark stain (which three types of anterior pituitary cells are basophils)
What are chromophobes?
Anterior Pituitary Cell Types and Hormones:
Acidophils - most abundant hormone producing cell type (light stain)
- somatotrophs : GH
- lactotrophs: prolactin
Basophils: dark stain
- corticotrophs: ACTH
- gonadotrophs: LH and FSH
- Thyrotrophs: TSH
Chromophobes have clear appearnace, paracrine actions, often pituitary tumors are in these and show no symptoms
Explain the regional distribution of anterior pituitary cell types:
Are are the kind of cells that are located on the outside?
Inside
Look at the diagram:
Most somtotrophs and lactotrophs are located outside
KEY CONCEPT:
Draw out the differences between the hypothalamus to anterior pituitary general axis vs the hypothalamus to posterior pituitary axis
AVP: (posterior pituitary tract)
AVP is made in the _____ neurons within the hypothalamus, travels down the ________ tract to the posterior pituitary, where it goes into systemic circulation and targets _____ and _____
AVP: is processed as a _____ peptide
What does it look like as a preprohormone and a prohormone? (which copeptide does AVP vs OXY have)
AVP is made in the magnocellular neurons within the hypothalamus, travels down the axons (neurohypophysial tract) to the posterior pituitary where it goes into systemic circulation and targets the vasculature and the kidneys.
AVP is a nonapeptide (9 AA)
Transcribed as a preprohormone (means signal peptide still attached)
Prohormones: AVP and neurophysin II, and OXY is neurophysin I
AVP is made in cell bodies within the ___ and ___
The PVN has two types of cells: magnocellular and parvocellular
Only _______ neurons project to the posterior pituitary
Parvocellular neurons that contain AVP project to ___ and are important for _____
AVP in magnocellular SON and PVN is important for maintaining _______
AVP is made in cell bodies in the PVN and SON
PVN has two types of cells: magnocellular and parvocellular
Only magnocellular neurons project to the posterior pituitary
Parvocellular PVN neurons that contain AVP project to median eminence and are important for regulating mood/anxiety/stress
AVP in magnocellular SON and PVN is important for maintaining fluid balance
***AVP Release Posterior Pituitary:
Explain the signaling pathways that trigger AVP release from the posterior pituitary and how sensitive they are relative to one another
- Plasma osmolarity
2, Significant blood loss
- Plasma Osmolarity (VERY sensitive)
When plasma osmolarity increases, the osmoreceptors in the brain shrink. The shrinkage of those osmoreceptors decreases the inhibition that is normally on magnocellular neurons, allowing them to release AVP and target vasculature (constrict to increase BP) and kidneys (increase water reabsorption)
- Significant blood loss (less sensitive, have to lose 5-10% of blood volume):
A decrease in mean arterial BP causes a decrease in baroreceptor stretch and thus a decrease in baroreceptor firing, the brain then increases sympathetic tone. Also, the osmoreceptors now respond to lower osmolarity (shifts curve to left)
AVP Targets:
The first target of AVP is the vasculature
AVP as a peptide hormone will bind to ______ receptors to cause _______
What does this do to vascular resistance?
AVP Targets:
First target of AVP is the vasculature
AVP as a peptide hormone will bind to a surface receptor, and for vascular smooth muscle the receptor is called the V1 receptor to cause vasoconstriction
AVP causes vasoconstriction- increases vascular resistance
AVP:
AVP targets the vasculature and the ____ (which organ)
On the _____ it binds to the ___ receptor
AVP causes ____ insertion on the cell membrane facing the lumen, thus causing water _____
AVP:
second target is the KIDNEY
On the kidney it binds to the V2 receptor
AVP causes AQP2 insertion in cell membrane facing the lumen, increases water reabsorption
SUMMARY of AVP affects:
In the vasculature, AVP binds to the __ receptor, causing _____ and an ____ in vascular resistance
In the kidney, AVP binds to the ___ receptor, causing _______ and thus ______
In the vasculature, AVP binds to the V1 receptor, causing vasoconstriction and an increase in vascular resistance
In the kidney, AVP binds to V2 receptor, causing AQP2 insertion in cell membrane facing the lumen, increasing water reabsorption
OXYTOCIN:
Oxytocin causes smooth muscle _____
Where does it have its effects, and what does that cause?
Example of _____ feedback loops
Oxytocin:
Oxytocin causes smooth muscle contraction
- Breast: contracts myoepithelial cells and causes milk ejection
-
Uterine contraction: giving birth
(note: “PITOCIN” is synthetic oxytocin used to induce labor)
POSITIVE FEEDBACK
HPL Axis:
What are the three parts of the HPL Axis
Explain the axis briefly
HPL Axis: (regulation of growth overall)
Hypothalamus : arcuate nucleus makes GHRH
P: anterior pituitary somatotrope releases GH
Liver: releases IGF-1
GHRH is made by the arcuate nucleus and is released into portal vein, targets pituitary somatotrope to activate PKA and release GH. The three major targets of GH are muscle, adipose tissue, and the liver (and the liver is what makes IGF-1)
Somatostain is the ______ of GHRH
______ is made in the hypothalamus and pancreatic delta cells (_____)
Most of the somatostatin in the body is made where?
Somatostatin is the inhibitor of GHRH (it does this two ways, explained on another card)
SS14 is made in the hypothalamus and pancreatic delta cells PC1/PC2
SS14 is the inhibitor of GHRH
Most of the somatostatin in the body is SS28 and that is made by D cells in the stomach and cleaved by the enzyme furin
GHRH and somatostatin:
Somatostatin inhibits GHRH in two ways:
1.
2.
Also, explain what graphs would look like that compare the relationship between somatostatin, GHRH, and GH levels (somatostatin and GHRH/GH have an ____ relationship_
GHRH and somatostatin:
Somatostatin inhibits GHRH at two levels:
- Somatostatin modulates GHRH pulsatility in the hypothalamus (decreasing its pulsatile frequency)
- Somatostatin inhibits PKA in the pituitary thereby inhibiting GH release
There is an inverse relationship between somatostatin levels and levels of both GHRH and GH
Key Concept: GH Intermediates
Many downstream target organ effects of GH are mediated through ______
GH stimulates ____ production in the ____
Key Concept: GH Intermediates:
Many downstream target organs effects of GH are mediated through IGF-1
GH stimulates IGF-1 production in the liver (and this stimulation is insulin dependent)
HPL Axis:
GHRH is released from hypothalamus and travels to the anterior pituitary where it stimulates PKA to release GH.
GH has three major targets: _____, ____, _____
GH stimulates IGF1 in the liver (____ dependent)
Explain the feedback loop of IGF-1 in the HPL axis
HPL Axis:
GHRH is released from hypothalamus, travels to anterior pituitary and activates PKA to create and release GH
GH has three targets: adipose tissue, muscle, and the liver
In the liver, GH stimulates IGF-1 production as long as there is insulin (IGF-1 stimulation is insulin dependent)
IGF-1 acts as negative feedback: in a long loop, IGF-1 inhibits GH release at the pituitary gland AND IGF-1 stimulates somatostatin in the hypothalamus (both of these cause negative feedback)
Explain the negative feedback loop that IGF-1 has on the HPL axis
IGF-1 is stimulated by GH in the presence of insulin
IGF-1 asserts negative feedback on the HPL axis via:
inhibiting GH release at the pituitary somatotropes
AND stimulating somatosatin (so that somatostatin can inhibit the pathway as well)
Explain the Physiological Effects of GH (and IGF-1) in the fed vs fasted state
Fed State:
- GH stimulates liver to increase RNA and protein synthesis, and to increase IGFBPs and IGFs
- GH stimulates muscle to increase AA uptake and increase protein synthesis
GH goal in fed state is to increase lean body mass
- also in fed state, IGF-1 will increase organ size and bone size
Fasted State:
- in fasted state, GH will cause adipose tissue to decrease glucose uptake and increase lipolysis
- Liver: increase gluconeogenesis
- Muscle: decrease glucose uptake
Explain what happens in the following scenarios within the HPL axis:
- eating only protein
- eating a donut
- fasted state
- eating only protein: amino acids stimulate GHFH, increase GH levels, increase IGF-1 levels, increase protein synthesis and growth
- donut: low AA, high glucose will inhibit GHRH
- fasting state: low glucose stimulates GHRH but no IGF-1, GH will then increase (without IGF-1 increase), and that GH will ause caloric mobilization in lipids
IGF-1 peaks are critical during _____ periods
IGF-1 levels are at the highest during _____ (life stage)
IGF-1 peaks during critical growth periods - highest during puberty
What are the main stimulators and inhibitors of GH?
GH is increased by ___, ____, ___
GH is decreased by ____, ____, ____
Stimulators and Inhibitors of GH:
Main stimulator of GH is GHRH, other stimulators include dopamine, NE/Epi (exercise/stress), Amino Acids (protein building), and thyroid hormone
Main inhibitor of GH is somatostatin, other inhibtors of GH are IGF-1 (negative feedback loop), glucose (hyperglycemia), and free fatty acids (obesity)
GH is increased by stress, exercise, starvation
GH is decreased by aging, high blood glucose, and obesity
GH Excess- somatotrope tumor (20%)
Explain the differences between gigantism and acromegaly:
Gigantism: extremely ____, occurs before _____
Acromegaly: usually diagnosed in ____
- gradual enlargement of ____ and ____
- changes in facial features
- possible increased organ size
- most often caused by ___
GH Excess - somatotrope tumor (20%)
Gigantism - extremely rare, occurs before the closing of the epiphyseal plate during childhood
Acromegaly: usually diagnosed in middle age
- gradual enlargement of hands and feet
- changes in facial features
- possible increased organ size
- most often caused by pituitary adenoma
GH Deficiency:
Dwarfism (children): related to GH
- Laron Syndrome: genetic defect in _____, causing ______ of IGF-1. Plasma GH levels are_____
- African Pygymy (explain)
Adult GH Deficiency:
- caused by _____
- increased ___ deposition, muscle wasting
- risk of fractures, reduced bone density
GH Deficiency:
Dwarfism (children): related to GH
-
Laron Syndrome: genetic defect in GH receptor - NO production of IGF-1. Plasma GH levels are normal to high (lack of negative feedback)
- treatment for laron syndrome is giving the pt IGF-1
- African Pgymy: partial defect in GH receptor, some IGF-1 response
- plasma levels of Gh normal
Adult GH Deficiency:
- caused by pituitary tumor/surgery
- increased fat deposition and muscle wasting
Explain what you would expect to see in terms of GH levels for:
Laron Syndrome
African Pgymy
Laron Syndrome: genetic defect in GH receptor, causing no production of IGF-1. Due to that lack of negative feedback, GH levels are normal to high
African Pgymy: partial defect in GH receptor, some IGF-1 response, plasma GH levels are normal
Prolactin:
Prolactin is made in pituitary ______
Prolactin is tonically inhibited by ______
Early antihypertensive drugs inhibited ___, thereby causing what?
Prolactin is released in response to ____
Prolactin:
Prolactin is made in pituitary somatotropes
Under normal conditions, dopamine tonically inhibits prolactin
early antihypertensive drugs inhibited dopamine, caused prolactin release and caused galactorrhea (milk production in breasts)
Prolactin is released in response to suckling (positive feedback loop)
Prolactin is important in milk production
_____ inhibits prolactin
Prolactin inhibits _______
(so in instances where prolactin is abnornally high, then what?)
Dopamine inhibits prolactin
Prolactin inhibits GnRH
At times where prolactin is high, you will have diminished FSH and decreased menstral cycles
Prolactin:
Prolactin hormone is in the same family as ___ hormone
This means that ___ can bind the prolactin receptor, and prolactin can bind the ___ receptor
Explain what they means for acromegaly patients
Prolactin
Prolactin is in the same family as GH hormone
This means that prolactin can bind the GH receptor. and GH can bind the prolactin receptor
In patients with acrogemaly (high GH levels), the extra GH can bind to prolactin receptors and cause galactorrhea (milk production)
Prolactin Excess:
- prolactinomas are common pituitary adenomas
- cause _____ prolactin levels
- causing ______ (increased milk production)
- reproductive ________
Prolactin Deficiency:
- Sheehan’s syndrome (explain what this is…. it was in small group)
Prolactin Excess:
- prolactinomas are common pituitary adenomas
- cause increased prolactin levels
- causing galactorrhea (milk discharge from breast)
- reproductive dysfunction (prolactin inhibits GnRH release)
Prolactin Deficiency:
- Sheehan’s Syndrome:
- occurs as a result of hemorrhage during childbirth
- causes pituitary cell death
- affects lactotrophs, causing an inability to produce milk, and also causes loss of pubic hair
Predict the GH level for the following scenarios:
- Insulin induced hypoglycemia should cause an ___ in GH levels
- Administration of IGF-1 should cause an __ in GH levels
- Insulin induced hypoglycemia should cause an increase in GH levels (low blood sugar stimulates GHRH release, thereby increasing GH levels)
- Administration of IGF-1 causes a decrease in GH levels (due to negative feedback)
