12. ENDO E1: Adrenal Gland

Here is a good review pic.

oh my woooooww

1. What are the 2 effects of mineralocorticoids? 2. What are the 2 effects of glucocorticoids?

1. a) retention of sodium ions and water by kidney b) increased blood volume and blood pressure 2. a) proteins and fats broken down and converted to glucose, leading to increased blood glucose b) immune system may be suppressed

*Cushing's disease:* what are the 11 main symptoms of cushing's disease?

1. red cheeks 2. fat pads (buffalo hump) 3. Thin skin 4. High blood pressure 5. thin arms and legs 6. poor wound healing 7. pendulous abdomen / central fat deposition 8. bruisability or ecchymoses 9. moon face 10. abdominal straie 11. osteoporosis/ broken bones

*Catecholamine receptors*: 5. Which receptor does epinephrine have the higher affinity for?

5. Epinephrine has higher affinity for beta 2 receptors

How would under stimulation/production affect a patient?

Addison's disease just read the pic for the symptoms

*Hormones produced by the Adrenal Cortex:* 1. Aldosterone is what type of corticoid? 2. Where is it produced? 3. What does it do? and it acts on what organ? it is apart of what system? 4. Keeps homeostasis for what 2 things?

Aldosterone 1. mineralocorticoid- 2. Zona glomerulosa 3. regulates salt and water retention), in the kidney, part of the renin system 4. functions in salt and water homeostasis

*Hormones produced by the Adrenal Cortex:* 11. Dehydroepiandrosterone is a what? 12. where are they produced? 13. What is a precursor to? 14. how much is known about the regulation of their secretion? 15. follows a similar diurnal pattern as what other adrenal cortex hormone?

Androgens- dehydroepiandrosterone 11. Androgen 12. Zona reticularis 13. DHEA/S, precursor to sex hormones 14. Very little is know about the regulation of their secretion 15. Some (DHEA) follow a similar diurnal pattern as cortisol

*Hormones produced by the Adrenal Cortex:* 5. Cortisol is what type of corticoid? 6. Where is it produced? 7. What does it do? 8. it is released in response to what? 9. Influences what with glucose? 10. it keeps homeostasis for what 2 things?

Cortisol 5. glucocorticoid- 6. Zona Fasciculata 7. increases plasma glucose 8. released in response to stress 9. influences glucose utilization, 10. immune and inflammatory homeostasis

What would over stimulation/production cause in a patient?

Cushing's disease Hypercortisolism usually occurs due to high levels of ACTH from pituitary adenoma

*Adrenal Medulla:* 4. Epinephrine is a responder to WHAT? 5. What does epinephrine influence?

Epinephrine 4. responder to stress such as hypoglycemia/exercise 5. influences energy metabolism and cardiac output

*Catecholamine receptors*: 1. What are the 5 receptor types for catecholamines? 2. What is the primary mechanism of action for each? (i.e. does it increase or decrease cAMP, one of the receptors uses other things other then cAMP)

1&2. alpha 1 - Increased IP3 and Ca2+ and DAG alpha 2- decrease cAMP beta 1 - Increase cAMP beta 2 - increase cAMP beta 3 - increase cAMP

*The adrenal gland:* 1. What are the three layers of the adrenal cortex? 2. What does each layer secrete?

1&2. from top to bottom Zona Glomerulosa - Mineralocorticoids Zona Fasciculata - Glucocorticoids Zona Reticularis - Androgens Just FYI that the fasiculata does make some androgens and the reticularis makes some glucocorticoids.

*Degradation of Catecholamines:* 1. how long are the affects of the catecholamines? 2. why? 3. What are the 2 enzymes that break down catecholamines?

1. *action of catecholamines is brief ~ 10 seconds* 2. The breakdown of epinephrine and norepinephrine is fast! 3. COMT: catecholamine-O-methyltransferase MAO: monoamine oxidase

*Aldosterone:* 1. comprises how much of the mineralcorticoids in the body? 2. is it the most potent of all the mineralcorticoids? 3. Why will Aldosterone only be produced in the glomerulosa cells?

1. 90% 2. yes thats why i asked 3. this is b/c only glomerulosa cells contain *aldosterone synthase* the enzyme to make it

1. what causes production of glucocorticoids and epinephrine and norepinephrine? 2. what causes release of glucocorticoids and epinephrine and norepinephrine?

1. ACTH 2. CNS for epinephrine and norepinephrine ACTH for glucocorticoids

*Aldosterone secretion:* 1. What are the 3 different pathways for aldosterone secretion? 2. What 2 are similar? 3. So what 2 pathways if activated would give you a bigger aldosterone response?

1. ANG II, increased [K+] and ACTH 2. ANG II and increased [K+] are similar 3. ACTH with either ANG II or increased [K+] She said the rest of info on the slide wasn't important but here is the picture of it for your reading pleasure.

*adrenocoritcal steroids production:* 1. All the adrenocortical steroids will be made from what molecule? 2. Main source of #1 is from what? 3. So the cells in the adrenal cortex will have lots of receptors for [#1 or #2?]

1. Cholesterol 2. LDL 3. LDL this allows them to make all the wonderful steroids in the picture

*Norepinephrine and Epinephrine are Synthesis:* 1. where inside the cell is norepinephrine created? 2. Where in the cell is PNMT found? 3. Why is some norephinephrine found in small quantities being released with epinephrine?

1. Chromaffin granule 2. cytosol 3. it is residual b/c it didn't get converted by the PNMT enzyme before being exocytosed

*Glucocorticoids:* 1. what is the main one and how much of the glucocorticoids does it comprise itself of? 2. is #1 the most potent? 3. Are there synthetic glucocorticoids that are more potent then #1? 4. What are the 3?

1. Cortisol it is 95% of glucocorticoids 2. Yes it is the most potent Glucocorticoid 3. yes yes yes 4. prednazone methylprednazone dexamethazone even more potent then corisol

*Cortisone (FYI) :* 1. cortisone is used to treat what? 2. Cortisone is converted to cortisol where? 3. Cortisol is converted to cortisone where? and why?

1. Cortisone used to treat inflammatory disorders 2. Cortisone is converted to cortisol in adipose and liver 3. Cortisol is converted to cortisone in renal distal tubule and collecting ducts, because cortisol can interfere with aldosterone regulation in kidney

*Adrenal Androgens:* 1. What are the 2 main androgens? 2. what zones produce this and which one is the most important?

1. DHEA and androstenedione 2. produced by the zonae fasciculate/reticularis but mostly reticularis

1. What is the short-term stress response? 2. What is the long-term stress response?

1. Epinephrine and norepinephrine 2. Mineralocorticoids, and glucocorticoids

*cortisol:* 1. Cortisol helps you do what in the morning? 2. is cortisol levels high or low in the mornings? 3. What is this rhythm called that cortisol helps control?

1. GET UP 2. HIGH 3. Circadian rhythm

What are the 5 effects of epinephrine and norepinephrine?

1. Glycogen broken down to glucose; increased blood glucose 2. Increased blood pressure 3. Increased breathing rate 4. Increased metabolic rate 5. Change in blood flow patterns, leading to increased alterness and decreased digestive and kidney activity.

*Addison's disease* 1. High ACTH causes what? 2. low cortisol leads to what 4 things?

1. Hyperpigmentation 2. a) nausea, vomitting b) fatigue c) hypotension d) hypoglycemia

*Review:* 1. Higher centers affect what to release CRH? 2. CRH then activates what? 3. #2 then releases what b/c of CRH? 4. #3 then acts on what? 5. #4 releases what b/c of #3? 6. #5 then inhibits what?

1. Hypothalamus 2. Anterior pituitary 3. ACTH 4. Adrenal Cortex 5. Cortisol 6. Cortisol has negative feedback on Hypothalamus and Anterior pituitary

*Mineralocorticoid-Aldosterone:* *1. What is the major action of aldosterone?* *2. It has a similar action in what other 3 things?* 3. Mineralocorticoid receptors are also found in what other 3 tissues but their role is unclear?

1. Major action is to stimulate *kidney reabsorption of sodium and secretion of potassium* 2. Similar action on salt and water transport in *colon, salivary and sweat glands* 3. Mineralocorticoid receptors are also found in myocardium, liver, brain and other tissues but their role is unclear

*Adrenal Glands Embryological Origins:* 1. The medulla comes from what type of embryological origin tissue?(hint: not one of the main three) 2. The cortex comes from what embryological tissue layer/type?

1. Medulla-neuroectodermal (neural crest cells) tissue 2. Cortex-mesodermal tissue

*cortisol secretion mechanisms:* 1. what are the 3 types of stress that can cause release of cortisol and what are examples of each? 2. These stresses act on what?

1. Physical - running lifting something heavy emotional - relationships work biochemical - most common hypoglycemic conditions. 2. the hypothalamus

*Glucocorticoids- Cortisol:* 1. What are the 8 target tissues? 2. Which ones are the main 3?

1. Target tissues Liver Fat Muscle Bone Skin Viscera Hematopoietic and lymph tissue CNS 2. Liver, Fat, and Muscle

*Adrenal Medulla:* 1. What does it produce?(general term) 2. What are the 2 specific molecules from #1? 3. What signals the medulla to produce the things in #2? 4. What signals the medulla to release the things produced in #3?

1. The adrenal medulla produces catecholamines 2. (primarily epinephrine and small amounts of norepinephrine) 3. ACTH 4. Sympathetic innervation AP's

*Synthesis of Catecholamines:* 1. This is under the control of what axis? 2. ACTH stimulates the synthesis of what specifically? 3. Cortisol increases what enzyme? 4. What does the enzyme in #3 do? 5. Release of epinephrine is triggered by what control?

1. Under control of the *CRH-ACTH-cortisol axis* 2. ACTH stimulates synthesis of *DOPA* 3. Cortisol increases *PNMT enzyme* 4. This enzyme is mostly found in the medulla and it takes norephinephrine to epinephrine. 5. Release is triggered by CNS control

*Cortisol in the blood plasma:* 1. 90% of cortisol is bound to what in the blood? 2. WHY 3. 7% of cortisol is bound to what? 4. only 3-4% of cortisol is what?

1. ~ 90% is bound to *corticoid-binding globulin* (CBG or transcortin 30 fold affinity for cortisol vs aldosterone) 2. This is so it won't be secreted in the kidneys also it increases the half life to 60-90 minutes. This also helps there to be a higher amount of cortisol in our system. 3. ~ 7% bound to albumin 4. Only 3-4% free circulating cortisol

*cortisol secretion mechanisms:* 12. ACTH will tell the adrenal cortex to do what? 13. What will have negative feedback on the anterior pituitary and the hypothalamus?

12. release Cortisol into the body 13. Cortisol

*cortisol secretion mechanisms:* 3. what is another mechanism that causes release of cortisol? (it is a rhythm) 4. normally do you have a high or low level of cortisol when going to sleep? why? 5. In the morning do you have a high or low level of cortisol? why? 6. this import acts on what?

3. Diurnal rhythm 4. LOW- so you can go to sleep 5. HIGH- helps you wake up 6. The hypothalamus

*The adrenal gland:* 3. Cortisol is an example of what type of hormone and what part of the adrenal gland does it come from? 4. Aldosterone is an example of what type of hormone and what part of the adrenal gland does it come from? 5. DHEA and androstenedione is an example of what type of hormone and what part of the adrenal gland does it come from?

3. Glucocorticoids - cortex- zona fasciculata 4. Mineralocorticoid- cortex - zona glomerulosa 5. Androgens - cortex- zona reticularis

*Glucocorticoids- Cortisol:* 3. What is the action of cortisol on the liver fat and muscle? 4. #3 is accomplished by what 3 mechanisms? 5. This can lead the body to what? 6. Fat is redistributed from where to where on the body with cortisol?

3. Increase plasma glucose 4. gluconeogenesis, AA metabolism, and lipolysis 5. Hyperglycemia 6. *Fat redistributed from *extremities* to *face and trunk*

*Addison's disease* 3. low androgens cause what? 4. are the mineralocorticoids usually normal?

3. Loss of pubic hair in women 4. usually normal mineralcorticoids

*Adrenal Androgens:* 3. Males adrenal androgens have [lots or little?] importance? 4. testes produce their own what? from choesterol

3. Males: adrenal androgens have *little* importance, 4. testes produce their own testosterone from cholesterol

*Catecholamine receptors*: 3. What is the examples of tissue distribution for each receptor?

3. alpha 1 - Sympathetic postsynaptic nerve terminals alpha 2 - Sympathetic presynaptic nerve terminals; beta cell of pancreatic islets beta 1 - Heart beta 2 - Liver; smooth muscle of vasculature, bronchioles, and uterus beta 3 - Liver; adipose tissue

*Degradation of Catecholamines:* 4. Epinephrine gets broken down to WHAT? via MAO? via COMT? 5. Norepinephrine gets broken down to WHAT? via MAO? Via COMT?

4. Epinephrine ---->COMT----> Metanephrine Epinephrine ---->MAO----> Dihydroxymandelic acid 5. norepinephrine ---->COMT----> Normetanephrine Norepinephrine ---->MAO----> Dihydroxymandelic acid

*Mineralocorticoid-Aldosterone:* 4. What cells in the kidney monitor the levels of Na+ and water? 5. these cells tell what cells to create renin? 6. renin then does what? 7. This product is then turned into Angiotensin II where and by what? 8. Angiotensin II then goes where to create aldosterone?

4. Macula densa cells 5. Granular cells or juxtaglomerular cells 6. renin changes *angiotensinogen to angiotensin I* 7. Angiotensin I is converted to Angiotensin II by *ACE in the Lungs* 8. Goes *to the adrenal cortex* where it *makes aldosterone* which then *goes and acts on the kidney*

*cortisol:* 4. The circadian rhythm is controlled by WHAT? nucleus of the hypothalamus that receives input from the retina? 5. Do blind people have a circadian rhythm? 6. what is the mechanism for the hypothalamic neurons pulses of secretory activity?

4. The suprachiasmatic nucleus of the hypothalamus receives input from the retina to control circadian rhythm. 5. Blind people lose circadian rhythm. 6. The mechanism for the hypothalamic neurons pulses of secretory activity is not yet understood.

*Catecholamine receptors*: 4. What is the example of the actions to the tissues for each receptor?

4. alpha 1 - increase vascular smooth muscle contraction alpha 2 - inhibit norepinephrine release; inhibit insulin release beta 1 - Increase cardiac output beta 2 - Increase hepatic glucose output; decrease contraction of blood vessels,, bronchioles, and uterus beta 3 - increase hepatic glucose output; increase lipolysis

*Adrenal Androgens:* 5. Females adrenal androgens are the [major or least] source of precursor androgens? 6. ovaries utilize WHAT? to make 17 beta-estradiol? 7. can ovaries also produce 17 beta-estradiol from cholesterol on their own?

5. Females: adrenal androgens are the *major* source of precursor androgens, 6. ovaries utilize *adrenal androgens* to make 17ẞ-estradiol 7. YES ovaries can also produce it from cholesterol on their own

*Degradation of Catecholamines:* 6. Normetanephrine gets broken down to WHAT? via MAO? 7. Metanephrine gets broken down to WHAT? via MAO? 8. Dihdydroxymandelic acid gets broken down to WHAT? via COMT?

6. Vanillylmandelic acid (in urine) 7. Vanillylmandelic acid (in urine) 8. Vanillylmandelic acid (in urine)

*Glucocorticoids- Cortisol:* 7. What is the action of cortisol on bone? 8. What is the action of cortisol on skin and viscera?

7. bone metabolism; reduce mineral density 8. wasting of fat and supportive tissues produces thinning and fragility of skin and vessels

*cortisol secretion mechanisms:* 7. Small-bodied neurons in the hypothalamus synthesize and secrete WHAT which later goes on to increase cortisol? 8. What portal vessels carry molecule in #7 to the [anterior or posterior?] pituitary?

7. corticotropin releasing hormone (CRH) 8. LONG portal vessels carry CRH to the *anterior pituitary

*Adrenal Androgens:* 8. Zonae fasciculate/reticularis will also make small amounts of what 2 things?

8. Zonae fasciculate/reticularis will also make small amounts of *testosterone and 17ẞ-estradiol*

*Glucocorticoids- Cortisol:* 9. What is the action of cortisol on hematopoietic and lymph tissue? 10. What is the action of cortisol on the CNS?

9. Anti-inflammatory; reduced immune activity 10. unknown mechanisms but can cause mood swings, depression, and anxiety.

*Degradation of Catecholamines:* 9. Since Epinephrine and norepinephrine get degraded so quickly what do you measure to determine total catecholamine production? 10. What is the main molecule that you will be able to check quickly in the urine for epinephrine production?

9. Catecholamines, metanephrines, and vanillylmandelic acid (VMA) can be measured To determine total catecholamine production 10. Vanillylmandelic acid

*cortisol secretion mechanisms:* 9. what cells in the anterior pituitary are going to receive the CRH? 10. the cells in #9 will release what when they receive the CRH signal? 11. Where does the hormone in #10 go to?

9. corticotrophs cells 10. ACTH 11. well it goes systemically through the blood but it acts on the *adrenal cortex*

****MEMORIZE THE PATHWAY ON THE BACK OF THE CARD SUPPPPPERRRR IMPORTANT Y'ALL****

JK she said you don't have to memorize it just be familiar with it because some people have mutations in the enzymes. might slow down or stop the production of certain hormones

List the different zones of the adrenal gland and the main steroid produced there.

Medulla- epinephrine Zona reticularis- DHEA Zona fasciculate- Cortisol Zona glomerulosa- Aldosterone