Chapter 11 Endocrinology Flashcards
Two types of Adrenal glands
1) Adrenal medulla
2) Adrenal Cortex
Adrenal Medulla secretes what two hormones in the bloodstream? What stimulates the Adrenal Medulla?
Epinephrine & Norepinephrine
Adrenal Medulla is stimulated by the sympathetic nervous system.
-Pre-ganlionic fibers on sympathetic side that reaches out and innervates the adrenal medulla.
Where is the adrenal medulla located in regards to the adrenal cortex?
The adrenal medulla is located anterior to the adrenal cortex.
The Adrenal Medulla releases what kind of hormones?
Catecholamine hormones that include epinephrine and norepinephrine
The two primary catecholamine hormones that the adrenal medulla release are _____________ and ____________. These hormones mediate ____________ effects.
Epinephrine and Norepinephrine. They mediate sympathoadrenal effects.
“fight or flight response”
List the sympathoadrenal effects that epinephrine and norepinephrine mediate
- Inc cardiac output
- Inc heart rate
- Dialated blood vessels to the heart
- Inc alertness
- Inc Respiratory rate
- Inc metabolic rate
C H D A R M
What are the metabolic effects from the catecholamines released from the adrenal medulla?
Metabolic effects of epinephrine and norepinephrine.
Overall increased Metabolic rate due to the mediation of circulating epinephrine acting as a hormone.
- Increase glycogenolysis in the liver
- Increase lipolysis in the adipose tissue
Epinephrine released from the adrenal medulla mediates its effects (inc glycogenolysis and inc lipolysis) at target tissues via activation of _________ that increase ______________.
Activation of G-protein coupled Receptors (GPCRs) that increase intracellular second messengers.
Activation of Beta receptor leads to increased intracellular cyclic AMP (cAMP).
Activation of alpha receptors lead to increased intracellular cytosolic calcium.
Activation of what increases intracellular second messengers when epinephrine is mediating effects at target tissues?
GPCRs
What are the two intracellular second messengers that are increased by epinephrine activating GPCRs at target tissues?
Increases intracellular cAMP
Increased Calcium
When B receptors of GPCRs are activated, what intracellular second messenger is impacted?
Cyclic AMP (cAMP)
When Alpha receptors of GPCRs are activated, what intracellular second messenger is impacted?
cytosolic calcium
Explain the steps involved in how B-adrenergic receptors impact intracellular Cyclic-AMP
- The hormone (epinephrine) binds to the B-receptor on the target cells plasma membrane.
- The B-receptor then activates the associated G-protein (heterotrimeric G-protein) on the cytosolic side.
- Once activated the G-protein has an alpha effect which means that the alpha subunit breaks apart and interacts with the downstream effector.
- The alpha subunit interacts with the downstream effector, Adrenylate cyclase, which is an enzyme found on the plasma membrane.
- Activation of the enzyme Adrenylate cyclase promotes production of cyclic-AMP from ATP. (ATP —> Cyclic-AMP)
- THIS IS HOW THERE IS NOW AN INCREASED INTRACELLULAR LEVELS OF CYCLIC-AMP
- Increased cyclic AMP has several downstream effects such as activation of kinases (PKA = “protein kinase A”) or “Cyclic AMP dependent protein kinases”.
When Cyclic AMP binds to these kinases, there is an increased catalytic functioning of these kinases to allow for the phosphorylation of other proteins. (these influence the activity/effects mediated by epinephrine)
What is the name of the downstream effector enzyme that is activated when epinephrine binds to B-adrenergic receptors on target tissues plasma membrane?
Adenylate cyclase
This enzyme converts ATP into Cyclic AMP.
Role of Adenylate Cyclase
Adenylate cyclase is an enzyme that activates the production of cyclic AMP.
It converts ATP into cAMP.
Adenylate Cyclase is activated by the binding of the alpha subunit of the G-protein that is mediated by epinephrine.
What does Cyclic AMP bind to in the cytosol that leads to the downstream physiological effects of epinephrine.
The increased cyclic AMP levels from the activation of the enzyme adenylate cyclase allows for cyclic AMP to bind to the regulatory subunit of Protein Kinase.
These kinases are called (PKA = “protein kinase A”) or “cyclic AMP dependent kinases as they are regulated by cAMP.
Activation of these protein kinases leads to the increases Phosphorylation of proteins.
The phosphorylation of proteins leads to the activation and deactivation of specific enzymes that lead to the effects mediated by epinephrine.
What is the catalytic job of Protein Kinases?
Phosphorylation of proteins.
These proteins then influence the activity of various metabolic enzymes that lead to the effects mediated by epinephrine.
alpha-adrenergic receptors influence:
Intracellular levels of Ca2+
What series of steps follows alpha-adrenergic receptor activation from epipinephrine released from the adrenal medulla
- epinephrine from the blood supply binds to alpha-receptor (GPCR) on the target cell’s plasma membrane
- This activates the associated G-protein and for the alpha subunit to interact with the downstream effector enzyme that is also located on the plasma membrane
- The alpha G-protein subunit interacts with the enzyme Phospholipase C
What is the downstream effector of alpha receptor activation?
Phospholipase C
What does the enzyme Phospholipase produce? What is its role?
Once the alpha subunit from the G-protein interacts with Phospholipase, there is a cleavage of the polar head groups of the phospholipid bilayer and their acyl tails attached to the membrane.
The polar head group forms IP3.
The acyl chain produces DAG.
What is IP3? What enzyme forms it? What role does IP3 play in intracellular levels of Ca2+?
Soluble intracellular second messenger in alpha-receptor activation from epinephrine.
IP3 is formed from the polar head groups which are cleaved from their acyl tails via the enzyme phospholipase C.
IP3 then binds to IP3 receptors (calcium channels) on the ER membrane. This opens the calcium channel and allows Ca2+ to move down its electrochemical gradient from areas of high concentration in the lumen of the ER to low concentration in the intracellular cytosol.
THIS IS HOW ACTIVATION OF ALPHA-RECEPTOR RESULTS IN AN INCREASED INTRACELLULAR CA2+.
As intracellular calcium levels increase, what protein does it bind to? What kinase does it bind to?
Calcium binds to a protein called calmodulin.
This calmodulin protein then binds to calcium calmodulin dependent kinases.
These kinases then increase in activity to lead to the typical downstream effects within these target cells.
Where are there high stores of calcium in cells?
Endoplasmic Reticulum of all cells.
SR in muscle cells.
Where is the adrenal cortex located in terms of the adrenal medulla ?
It lies outside of the adrenal medulla
Unlike the adrenal medulla which is controlled by the sympathetic nervous system (“fight or flight”), the adrenal cortex is controlled by what?
The Hypothalamic Pituitary Axis (HPA) controls the adrenal cortex.
When activated, what does the adrenal cortex secrete into the bloodstream?
Corticosteroids (also called steroid hormones)
How is the adrenal cortex arranged?
Its arranged into three layers or zones that release a different subset of steroid hormones into the blood supply.
-Zona glomerulosa
-Zona Fasciculata
-Zona Reticularis
What subset of steroids does the Zona Glomerulosa layer of the adrenal cortex release?
The zona glumerulosa releases mineralocorticoids. This kind of steroid largely affects the electrolyte balance within the blood supply.
Mineralcorticoids are a type of ______ that the ______ _____ layer of the adrenal cortex releases.
Mineralcorticoids largely affects the ______ balance in the blood supply.
A type of steroid that the Zona Glomerulosa layer of the adrenal cortex releases.
This steroid largely affects the electrolyte balance in the blood supply.
What subset of steroids does the Zona Fasciculata layer of the adrenal cortex release?
Glucocorticoids and sex steroids
-Glucocorticoids such as cortisol are important for the regulation of blood glucose
-Note that sex hormones are also released here but their primary source is the ovaries and testes
What subset of steroids does the Zona Reticularis layer of the adrenal cortex release?
Glucocorticoids and sex steroids
-Glucocorticoids such as cortisol are important for the regulation of blood glucose
-Note that sex hormones are also released here but their primary source is the ovaries and testes
Glucocorticoids
A steroid released from the Zona fasciculata and Zona Reticularis.
Ex: this includes cortisol
Glucocorticoids are involved in the regulation of blood glucose.
The biosynthesis of the steroid hormones (corticosteroids) from the adrenal cortex (Zona glomerulosa, Zona Fasciculata, and Zona Reticularis) are based on ________________.
Cholesterol
What mineralocorticoids does the Zona Glomerulosa release?
Aldosterone
Mineralocorticoids regulate _________
Electrolytes: Na+ and K+
Aldosterone
Increases sodium and water retention
Promotes potassium excretion in the kidneys
This is the hormone that serves to increase blood volume and pressure; and balances electrolyte concentrations
What is the major steroid hormone of the Zona Fasciculata and Zona Reticularis?
Cortisol
Cortisol
One type of glucocorticoid.
Cortisol will increase blood glucose levels
Glucocorticoids regulate ________
glucose and other metabolites.
They typically mediate catabolic effects.
Glucocorticoids also play a role in immune supression and inhibition of inflammation.
How does cortisol increase blood glucose levels?
Stimulates activation of glucogenesis
Inhibits glucose utilization in tissues
Can also provide energy by releasing and Increases fatty acid levels in the blood by stimulating lipolysis and fat cells.
What corticosteroid subset plays a role in immune supression and inhibition of inflammation?
Glucocorticoids
Steroid hormones are synthesized from __________.
Cholesterol
Where are steroid hormones produced in and secreted by?
Produced in and secreted by the adrenal cortex and gonads
Structure of cholesterol
Hydrophobic Four-ring fused structure
Hydrophobic molecule (small exception of hydroxyl group on left hand side)
Is cholesterol hydrophobic or hydrophilic molecule?
Hydrophobic molecule (small exception of hydroxyl group on left hand side)
Are the steroids derived from cholesterol going to relatively hydrophobic or hydrophillic?
Hydrophobic
How do steroid hormones travel through the blood stream? Why
They travel through the bloodstream by binding to “carrier proteins”.
They need carrier proteins in order to travel through the bloodstream because steroid hormones are hydrophobic and they want to stay away from the aqueous environment.
Two features of steroid hormones
1) Hydrophobic
2) Lipophilic
What do steroid hormones recognize and bind to?
Intracellular nuclear hormone receptors
“nuclear receptors”
“intracellular receptors”
Intracellular nuclear hormone receptors are ___________ factors
Transcription
Steroid Hormones Mechanism of Action
- Steroid hormones bind to carrier protein in the blood stream so it can carry it through the blood supply.
- Enters target cell via simple diffusion
- Hormone binds to receptor protein (transcription facter) in the cytosol.
- Hormone bound to the receptor protein allows translocation into the nucleus.
- The DNA binding domain of the receptor protein sits on the DNA strand
- Upregulates mRNA
- Protein synthesis
- Steroid hormone physiological response
Via what kind of transport does steroid hormones exit blood stream and enter target cell?
Simple diffusion
What are the two domains of the receptor protein for a steroid hormone?
- Ligand-binding domain- where the hormone binds
- DNA-binding domain– recognizes and sits down on certain sequences in the DNA.
-This is the transcription factor end of the molecule
What needs to happen for the hormone-bound receptor to act as a transcription factor?
Two monomers come together to form an activated homodimer.
Explain the hypothalamic-pituitary-adrenal axis in the negative feedback control of cortisol.
Stress info –> higher brain centers –> stimulates hypothalamus to release CRH –> CRH binds to the Anterior Pituitary –> Anterior pituitary releases ACTH
What does the hypothalamus release in response to stress? (HPA: neg feedback)
CRH
What detects CRH in the HPA Axis Negative Feedback Control?
Anterior Pituitary
What does the Anterior
Pituitary release in the HPA Axis Negative feedback control that ultimately leads to release of cortisol?
ACTH
What detects ACTH in the HPA Axis Negative Feedback Control?
Adrenal Cortex