Week 16- Unit 4 Flashcards
What are the alternative counter-regulatory hormones to focus on (5) ?
- Somatostatin
- Growth Hormone
- Catecholamines (norepinephrine and epinephrine)
- Glucocorticoids (cortisol - steroid hormones)
- Thyroid Hormone
What are the “peptide hormones” ? (4)
What do they all signal through?
Insulin
Glucagon
Somatostatin
Growth Hormone
-signal through binding of a cell membrane receptor
The Catecholamines ( nor and epinephrine) are _______ type hormones, they also signal through _______ ______ specifically the ___ or ____ adrenergic receptors.
Amine
Membrane receptors
Alpha or Beta Adrenergic
Glucocorticoids (cortisol) are ______ that signal through _______ receptors that function as ________ ________.
steroid
intracellular
transcription factors
Thyroid hormone is different from all the other hormones as it is a ________ type hormone but signals similar to the _______ types by binding to an ________ receptor and functioning as a transcription factor.
Peptide
Steroid
Intracellular
Insulin is secreted from ______ cells of the ______. It will suppress glucagon release from ______ cells.
(anabolic processes)
Beta
Pancreas
Alpha
Glucagon is secreted from _______ and _____ cells in pancreas. It can also stimulate the release of insulin in such a way that helps regulate ______ and ______ to maintain blood glucose. Without this regulation, Glucagon can precipitate __________ such as in diabetic ketoacidosis.
Alpha and L cells
GNG
Glycogenolysis
Hyperglycemia
Somatostatin is an general _______ for the release of other hormones. It is secreted as a ______ molecule much like insulin and glucagon, meaning it is secreted in _____ form that requires cleavage of the active peptide.
Inhibitor
Pro-molecule
Peptide
Somatostatin is secreted from several sites, mainly what 4 areas?
Hypothalamus
D cells of pancreatic islets
Central Nervous system
Gastric/intestinal mucosa
Somatostatin is secreted in response to what 3 MOLECULES mainly?
Glucose, Arginine, Leucine
What HORMONES can stimulate the release of Somatostatin ?
Glucagon
VIP
Cholecystokinin (CCK)- in Duodenum
Somatostatin will signal via a ______, activating an ______ G-protein which will then _______ adenylate cyclase. This will _______ cAMP.
GPCR
inhibitor
inactivate
decrease
Besides the main GPCR inhibitory pathway for signaling, Somatostatin can also activate several ______, _______ and _______.
Phosphatases
MAPK cascades
Ca+2 (calcium mediated signaling)
Somatostatin’s primary action is to decrease ______ will suppress the release of many hormones including what 4 ?
cAMP
Growth Hormone
TSH
Insulin
Glucagon
Somatostatin will also ______ gastric emptying by impacting the secretion of gastric and pancreatic _______.
Decrease
enzymes (required for digestion)
Glucagon can stimulate the release of both _____ and _____ in the pancreas.
Somatostatin (Delta cell)
Insulin (Beta cell)
Insulin will inhibit the release of ______ but does not necessarily effect the release of ______.
glucagon
Somatostatin
The action of Somatostatin being able to ____ both glucagon and insulin in a regulatory feeback look is necessary so Blood glucose can ______ again to stable levels before ______ is released again into the body.
inhibit
rise
insulin
Growth Hormone is a water _____ polypeptide with a very _____ half-life in circulation of ___ to ___ minutes.
soluble
Short
20 to 50
Growth hormone (GH) is composed of a _____ polypeptide chain in a spiral with ____ ____ bonds.
single
2 disulfide
Growth hormone is release from the ______ _____ gland. Starting at the ______ any number of stimuli can impact the release of _____ that will travel to the location of GH release.
Anterior pituitary
Hypothalamus
Growth Hormone Releasing Hormone (GHRH)
What are 4 examples of factors that can stimulate release of GHRH from they hypothalamus?
Sleep Rhythms Low blood glucose High blood AA Stress Exercise
After it is released from the Hypothalamus, GHRH binds to the ______ _____ of cells in the ______ ______. This results in the release of _____ by way of any number of second messengers including cAMP or Ca+ mediated signaling.
plasma membrane
Anterior Pituitary
Growth Hormone
After release from the anterior pituitary, Growth Hormone will travel in the blood to the ______ and interact with receptors similar to ______ _____ receptors. This will stimulate the release of ______ from the liver.
Liver
Jak-STAT
Insulin-like Growth Factor 1 (IGF-1)
IGF-1 will be similar to insulin by binding a plasma membrane _____ _____ for signaling. It regulates itself for feedback at several different levels.
Tyrosine kinase
Growth Hormone will feedback and inhibit the release of ______ in the Hypothalamus.
Similarly, _____ will feedback and inhibit its release from the Hypothalamus as well.
GHRH
IGF-1 (from liver)
IGF-1 can directly inhibit the release of _____ at the Anterior Pituitary gland. It will inhibit the release of _____ from the Hypothalamus, and then it will also STIMULATE the release of _______ from the Hypothalamus.
GH
GHRH
Somatostatin (will travel to inhibit release of GH at anterior pituitary)
The primary physiologic factors effecting stimulation of release of Growth Hormone depend on fuel availability. If Blood Glucose is _____ after meals , it will stimulate release of GH and GH helps reduce Glucose _____ and increases ______.
Low (GH helps increase blood glucose)
uptake
GNG
GH is released in response to ____ blood glucose and ______ blood levels after meals. The other three main stimulating factors are ?
low
AA
Sleep, Stress, Exercise
What will suppress the GH secretion at the physiological level after meals ?
High blood glucose after meals
High blood Fatty Acids
Release of GH can also be stimulated with pharmacological means such as addition of _______ or it can be inhibited by the introduction of _______.
GHRH
Somatostatin
Pathological states such as Starvation where energy is extremely low, will elicit the _____ of growth hormone release. This helps influence the pathways of ____ and _____ as a means of providing energy.
Stimulation
GNG
Lipolysis
Pathological states such as Obesity, Hypothyroidism, Hyperthyroidism will ______ growth hormone secretion.
suppress
For a GH receptor, they ______ upon ligand binding. However the receptors themselves lack _____ activity, so they are associated with _____ family of kinases.
dimerize
kinase
Jak2
The Jak2 (JAK) family of kinases that associate with GH receptor will phosphorylate the receptor after dimerization from ligand binding, this will then phosphorylate and activate ________, _______, or ______ signaling that all can have a cellular effect.
STAT (1,3,&5)
MAPKs
Phosphoinostitol kinases (PI3K)
GH as a physiological effect can be considered a means of _____ energy. It leads to a “muscle building” environment.
increasing
GH will effect the Adipose by ______ lipolysis by increasing the sensitivity of the tissue to _________. This will then in turn stimulate lipolysis by phosphorylation of ________.
This is a means of decreasing fat storage—>lean athletic physique.
increasing
epinephrine
Hormone sensitive lipase
In the Skeletal muscle, GH will increase ______ uptake and oxidization by the muscle.
This generates _____.
GH also increases ______ transport and uptake which will lead to increased _____ _____.
Free Fatty Acid (FFA - came from adipose)
ATP
AA
Protein Synthesis
In the liver, GH will ______ GNG and decreases ______ uptake to maintain blood levels, then increasing glycogen synthesis (even though counter intuitive, it is making energy and storing it too)
increase (GNG)
Glucose
In the liver, GH will also increase _______ uptake that will be oxidized to Acetyl CoA which increases substrate for ______.
FA
Ketogenesis
In the liver, because GH will decrease glucose uptake and increase ketogenesis (FA uptake too), this will contribute to ______ blood glucose levels and increased energy reserves.
elevated
Most importantly , GH will stimulate the release _____ and _____ that illicit the indirect effects of GH release on the body.
IGF-1
IGF-2
(2 Isoforms)
What cells in the Anterior Pituitary Gland will release Growth Hormone?
Somatotrophs
IGF can function in both an ______ and ______ way after being produced after the binding of GH to its Jak-STAT family Receptor on the liver.
Endocrine
Paracrine
IGF can act as a paracrine by binding to its own receptor on the ______. This receptor is similar to a ____ ___ (insulin like receptor with endogenous activity)
Liver
Tyrosine Kinase
The cascade initiated by IGF binding its own receptor in a Liver cell (paracrine) will cause a ________ response. This allows the cell to grow.
Mitogenic
As an autocrine, IGF will be similar to activites of ______ and it also has an influence on bones (long bones) on _____ or growth of the bone.
Insulin
Sulfation (needed for bone growth)
Growth Hormone will ______ glucose uptake in the Muscle, and _____ protein synthesis.
decrease
increases
Defects in GH are rare, but Excessive release of GH will cause _______ or Giantism.
Acromegaly
-Begins in young children or adolescents
What usually causes Acromegaly?
Tumor of somatotrope cells (secrete the GH from Anterior Pituitary)
Synthesis of Catecholamines like epinephrine and norepinephrine (stress induced) is initiated with ______ as the precursor.
Tyrosine
What organ will release Catecholamines like norepinephrine and epinephrine?
Adrenal Medulla
What 4 things may cause Catecholamine release from the adrenal medulla?
Exercise
Hypoglycemia
Pain
Hypoxia (lack of oxygen)
The major role of Catecholamines is to rapidly increase energy by increasing ______ in the adipose and ______ in the liver and muscle. They will also counteract the effects of _____.
Lipolysis
Glycogenolysis
Insulin (inhibits activity)
Epinephrine can enhance the activity of glycogenolysis in the liver using an _______ _______.
Alpha-agonist receptor
Binding of the Epinephrine to the Alpha-agonist receptor in the liver will activate ______ Which cleaves the membrane bound _____.
G-Protein
PIP2
What will the PIP2 be cleaved into in the beginning of Epinephrine induced activity on the liver cell?
- IP3
2. DAG
What does IP3 do in the epinephrine liver cell pathway?
stimulate release of Ca+ from the Endoplasmic Reticulum . This will then activate Calcium calmodulin
What will DAG do in the epinephrine pathway in the liver cell?
Activates Protein Kinase C which will phosphorylate Glycogen synthase to make it inactive
(leads to Glycogenolysis)
During exercise, Glucose in the muscles can be converted to ______ or to Pyruvate which is then transaminated to _______ and both shuttled to the liver for use as substrate for _____.
Lactate
Alanine
GNG
Glucocorticoids are all synthesized by starting with _________ and are for long term survival.
Cholesterol
Synthesis and secretion of Glucocorticoids is controlled by ________signaling.
neuroendocrine
any number of factors upon the Hypothalamus to signal release down the line
What two neurotransmitters will signal the brain to release ______ after they are signaled themselves by the Hypothalamus .
Acetylcholine
Serotonin
(monoamines above)
CRH
AcetylCholine and serotonin will target cells in the _____ ______ to release ______.
Paraventricular nucleus
CRH (cortisol releasing hormone)
CRH (cortisol releasing hormone) is released and will target cells specific in the pituitary gland, these cells will release ______ into general circulation.
ACTH - this will then travel and target the Adrenal gland to initial synthesis of Cortisol
Cortisol release from the Adrenal glands will provide a negative feedback loop by inhibiting the release of ____ from Hypothalamus and the _____ from the Pituitary.
CRH
ACTH
What is the rate limiting step in the synthesis of Cortisol from Cholesterol?
First step in synthesis pathway when Cholesterol is converted to :
Pregnenolone
In the muscles, Glucocorticoids will ______ protein degradation, ____ protein synthesis, and ______ glucose utilization.
Increase degradation
Decrease synthesis
Decrease utilizaiton
In the Adipose, Glucocorticoids will increase ________ for their fuel avaliability.
Lipolysis of TG
Glucocorticoids can increase the synthesis of ____________ in the Liver, this is the enzyme that is required for GNG.
PEP-carboxykinase
Glucocorticoids will _______ GNG and _____ glycogen storage. This occurs so that when_______ is released, there can be rapid entry of Glucose into the blood.
enhance
increase
epinephrine
Glucocorticoids (cortisol) will cause the normally opposed GNG and Glycogen synthesis to increase together by increasing _________ like AA, and increasing transcription of _________.
precursors (AA from muscles)
PEPCK (PEP carboxykinase)
Increases in Cortisol levels can result in the symptoms of _____ ____ and ______ _____.
Weight Gain
Central Adiposidy
Patient A - 41 year old female presents with High blood cortisol level, fatigue, weakness, lethargy, gained 40lbs in 2 months (central obesity and neck obesity) . Her physical examination was remarkable for ______ _______ with weight of 211 lbs.
Cushingoid appearance
In Patient A, Cortisol levels were elevated but ACTH was reduced. What does this suggest about the location of the defect?
Is the elevated cortisol a primary or secondary defect?
Location = Tumor in Adrenal Gland (high cortisol but low ACTH)
Primary Defect
In Patient A, the tumor in the adrenal gland will increase Cortisol output, this will cause negative feedback and inhibit _____ at the pituitary gland, and _______ at the Hypothalamus level.
ACTH release
CRH release
T4 is also called ?
T3 is also called?
(3,5,3,5)Tetra-iodothyronine
(3,5,3)Tri-iodothyronine
The two secreted Thyroid hormones called :
T4 -is also called ?
T3 -is also called?
(3,5,3,5)Tetra-iodothyronine
(3,5,3)Tri-iodothyronine
The majority of Thyorid hormone is bound, and it is only the small portion of free hormone that has ______ activity This free form is able to cross membranes freely and bind intracellular receptors.
Biological
Both T3 and T4 contain the skeleton of _______ residues. From here they are modified by the addition of _____ to the rings.
Tyrosine
Iodine
- T3 has 3 iodines
- T4 has 4 iodines
T3 and T4 production required the first synthesis of __________ and then are only released once it has been degraded.
Thyroglobulin
Synthesis of T3 and T4 starts with a ______ _____ that moves Na+ and Iodine into the Thyroid follicular cell.
Sodium-iodide symport
The movement of Iodine into the cell requires energy , so the symport is coupled to a _______
Na+-K ATPase
-pump to keep a electrochemical concentration gradient
Once in the cell, the Iodine is oxidized by ______ _______. This enzyme is located at the apical brush border.
thyroid peroxidase
The oxidation of Iodine once in the cell by thyroid peroxidase will form an ________ (I+). This will be what moves out of the cell into the Colloid space and reacts with ______residues.
Iodinium Ion
Tyrosine
Where is the Thyroglobulin protein stored that the Iodinium ion (I+) will react with?
Colloid space
To make T4 , you have a couping of 2 ___________
Di-Idonatedtyrosine (DIT)
To make T3 you have a coupling of ______ and ______.
DIT
MIT (monoiotosine-tyrosine residue)
Once the T3 and T4 are synthesis, they can be stored by staying bound to the _______ and remain in the _____ space.
Thyroglobulin (Tgb)
Colloid
The release of Thyroid hormone is different from other peptides as it is not released in a pro-form to be cleaved for activation, rather , the Tgb+T3 or T4 goes back into the cell through _______ from the colloid space.
Pinocytosis
Once the Tgb+T3 (T4) is in the cell again and out of the Colloid space, it is degraded by Lysosomes proteases , what then occurs?
The Tgb is degraded by lysosomes but the T3 and T4 are now free to be released into circulation out of the cell.
T4 is in ______ concentrations in the blood . However ______ is though to be the more biologically active form in the body.
higher
T3
T3 has a much shorter half-life between ____ and ____ days.
T4 has a half-life of about ______
1 and 1.5 days
7 days
One thing to note is that T3 and T4 are not found in appreciable amounts in ______ ______. It will mainly travel through blood bound to ____.
blood circulation
Tgb
A contributing factor that T3 and T4 are not readily in blood is because of what feature of seroids?
they can cross cell plasma membrane very easily and leave the circulation
Thyroid Hormones in the body are primarily controlled by _________ _______.
Thyroid-secreting hormone
TSH
TSH is released from the _____ in a circadium patter (wave like ).
Pituitary
What does the Hypothalamus release to target the Pituitary for release of TSH?
Thyroid Release Hormone (TRH)
Thyroid secreting hormone (TSH) from the anterior pituitary will reach the _____ and activate many different processes. It acts on a _______ ____ on the thyroid.
Thyroid
G-Protein coupled receptor
In the presence of TSH, then ____ and ____ will be released. These can impact the peripheral tissue, and specifically ____ will feedback and inhibit the activity of ____ and _____.
T3 and T4
T3
TRH
TSH
TSH is secreted from the Pituitary Gland and will bind a _______ receptor on the surface of the Thyroid ______ cells.
G-coupled Protein
Follicular
The activation of the G-protein coupled receptor by TSH will increase what 3 things?
- Expression for synthesis for Tgb
- Activity of Iodine Transporter increases (calcium mediated boost)
- Expression of Thyroid peroxidase (required for oxidation of Iodine before added to Tgb)
As the T3 and T4 bound to Tgb translocates through the cell through pinocytosis, ______ and ______ will digest the Tgb leaving T3 and T4 to diffuse outside cell.
Proteases
Peptidases
(from lysosomes)
What is the primary negative feedback regulating thyroid hormone release from the thyroid?
T3 will provide negative feedback at the pituitary gland preventing TSH from being released
T3 and T4 can be taken up by cells and will function as _____ _____ to illicit gene expression and ____ ______.
Transcription factors
Protein synthesis
The physiological changes caused by Thyroid hormones in the liver include:
- ________ Glycolysis
- ________synthesis
- Conversion of cholesterol to ____ salts
- TAG _______
- _____Hepatic Glucose secretion during fasting
Increased
CHolesterol
bile
synthesis increses
increases (increases sensitivity to epinephrine)
The same bipolar impact of Thyroid hormones on the liver is seen in adipose, it can both:
- Increase Lipolysis by_______
- Increase Lipogenesis by ______
- increases sensitivity to epinephrine (more break down of FA)
- direction determined by insulin and glucose levels
In the skeletal muscle, thyroid hormone will:
Increase glucose ______.
Stimulate protein ______.
Enhance Glycogenolysis by _______
uptake
synthesis
increasing sensitivity to epinephrine
In the pancrease, Thyroid Hormone will _______ sensitivity of beta cells to release ______. Thyroid hormone is actually _______ for sufficient release of insulin from the pancreas.
increase
Insulin
required
Thyroid Receptor (TR) is bound to DNA and in the abscence of T3/T4 functions as a ________ on gene expression. It can dimerize with different receptors (Homo dimers with same or Heterodimers with retinoic).
repressor
Binding of T3 to its Thyroid receptor on sitting on the DNA will cause a conformational change that activates the _______ _____. This is done through activation of a _____ ____.
Transcriptional complex
Histone Acetylation domain (HAC- domain)
-allows for opening of DNA and accessibility for transcription
Cortisol has its receptor in the ______ and its receptor will require ligand binding before translocation to the ______.
cytosol
nucleus (sit on DNA)
11 Year old female- Patient B- presents with high weight loss, heat intolerance, decline in grades at school, family hx for thyroid disease in both grandmothers. Test results: T3= very high at 374 TSH =low T4 = elevated This was confirmed as \_\_\_\_\_\_ disease.
Graves disease
-hyperthyroidism with thyrotoxicosis
In Patient B with Graves disease: T3= very high TSH = low T4 = high Why is the TSH low? Where is the defect?
TSH is low because there is inappropriate release of T3 from the Thyroid which is then inhibiting TSH release from Pituitary
Defect is in the Thyroid
To explain the heat intolerance in Graves disease:
Cold stimulus will signal Hypothalamus to release ________.. This will signal via _______ receptors on ________ cells.
Norepinephrine
-(Catacholamine)
G-coupled protein
Brown fat cells
To explain the heat intolerance in Graves disease:
The G-protein receptor activation will increase _________ which functions as an _________.
Thermogenin
Uncoupler
Thermogenin is an _______ and will dissipate the proton gradient and Heat is released as the gradient is not coupled to synthesis of _____.
uncoupler (protein)
ATP
At the same time the Epinephrine is stimulating Thermogenin activity in brown fat cells, it is stimulating _____ break down and making a lot of _____ and ____. This can be rapidly oxidized in ETS and since its uncoupled releases excess heat.
Triglyceride
NADH
FADH(2)
To explain the heat intolerance in Graves disease:
Elevated ____ will enhance the signaling of _______ in brown fat. This leads to an abnormal increase in FA oxidation and abnormal thermogenin production all leading to high heat production in ETS.
T3
Norepinephrine (NE)
-T3 increases cell sensitivity to E and NE
