Lecture 20 Flashcards
(21 cards)
Cortisol is what response hormone? What types of this is cortisol involved in?
Cortisol is a stress response hormone. It’s involved in all types of stress: Toxins, trauma, infection, exercise, hypoglycemia, emotional stress, pain, cold exposure
Why is cortisol (a steroid hormone that has function in suppressing the immune system) released during infection?
When the body is infected, its purpose is to kill that pathogen. But when our body goes overboard, other effects can occur and can cause too much damage to occur. Cortisol helps mitigate this response such that you are able to kill the pathogen in your body without killing yourself in the process.
What are the main functions of cortisol?
- increases blood sugar, aids in metabolism of fats, sugars and proteins
- suppresses immune system
- works with norepinephrine for short term memory responses (too much = impaired learning)
- decreases bone formation
- decreases insulin response (prevents GLUT4 transporters getting to cell membrane)
- inhibits collagen/protein synthesis and muscle protein uptake, increases protein breakdown
- acts as diuretic to flush out more water & increases sodium retention and potassium excretion in kidneys and intestines
How is cortisol stimulated to be released and what happens as a result of cortisol release? How does the negative feedback system associated with cortisol work to control cortisol synthesis?
Stressful situation –> hypothalamus –> stimulates release of CRH (corticotropin-releasing hormone) –> anterior pituitary to release ACTH (adrenocorticotropic hormone) –> adrenal cortex to make cortisol
Cortisol into the blood –> different target tissues to cause different responses –> goes back to inhibit the anterior pituitary and hypothalamus from secreting ACTH and CRH
Explain how ACTH acts on zona fasciculata cells to stimulate the production of cortisol.
ACTH is going to bind to GPCRs on zona fasciculata cells and stimulate the activation of adenylyl cyclase through G-alpha –> production of cAMP –> activation of PKA –> phosphorylation of proteins which increase transcription of steroid acute regulatory (StAR) protein –> translation of StAR protein –> mitochondria to allow for cholesterol transport into the mitochondria
Cholesterol gets acted upon by side chain cleavage enzyme (cytochorm P450SCC) in the mitochondria to produce delta-5 Pregnenolone –> sent to mitochondria to produce cortisol (released into the blood and go to target tissues)
ACTH increases the amount of LDL receptors such that more cholesterol is present in the cell for cortisol/steroid hormone synthesis
What does cortisol do in the muscles, the liver, and the adipose tissue?
a) liver: cortisol can increase gluconeogenesis, increase the amount and activity of enzymes for gluconeogenesis and glycogen storage (because cortisol creates a panic response and tells the body it needs glucose ASAP and may need it later)
b) muscles: cortisol will increase protein degradation, decrease protein synthesis, decrease glucose utilization, and decrease sensitivity to insulin (helps bring amino acids to the liver and keep blood sugar high)
c) adipose tissue: cortisol will increase the breakdown of fat, decrease glucose utilization, decrease sensitivity to insulin. (increasing lipolysis serves to mobilize glycerol backbones of triacylglycerides to increase blood sugar
Cortisol acts in your adipose tissue to mobilize glycerol, such that glycerol can be utilized to increase blood sugar. Why might this be problematic?
This increases the amount of fatty acids circulating in your blood. As a result, this can cause things like excess blood clots, more lipid deposits, development of plaques that are forming in your bloodstream as a result of stress.
Cortisol has what other response in addition to having a stress response? Why does this make sense and how does this process occur?
It’s also an anti-inflammatory. Cortisol has the effect of suppressing the immune system. Your immune response usually occurs when you have inflammation so if you’re suppressing the inflammatory response, you’re also suppressing your immune system as well.
It binds to glucocorticoid receptor to increase the production of an inhibitor (I-kB) of NF-kB (the transcriptional factor used for COX gene transcription.) This prevents eicosanoid/prostaglandin synthesis and prevents immune response. It also targets specific immune cells for apoptosis and degrades interleukins. Cortisol inhibits immune responses and decrease inflammation as well.
What is hydrocortisone and what is it used for? What about synthetic derivatives of hydrocortisone?
Hydrocortisone is used in oral administration, IV injection, and topical application. It is an immunosuppressive and anti-inflammatory. Synthetic derivatives include prednisolone (4x stronger) and dexamethasone (40x stronger.) Doctors can prescribe these strong anti-inflammatory drugs to help treat hives after epinephrine (epi-pen)
What factors increase cortisol levels in the body?
trauma/stressful events, sleep deprivation, anorexia nervosa, intense/prolonged exercise, variations of specific genes in the brain make certain people more susceptible to stress than other people, excess caffeine
People with anorexia nervosa have higher cortisol levels. Since they are not eating, they don’t have stores of fat to be able to produce the precursors for cholesterol synthesis. How is it that these individuals produce such high levels of cortisol, despite being severely malnourished?
Cortisol is one of the essential hormones that will still be produced. In the early stages of anorexia nervosa, more cortisol will be produced since malnutrition is stressful on the body. Increases in cortisol levels can be linked to the beginning of this eating disorder.
What are some methods to help decrease higher-than-normal cortisol levels?
- meditation
- dancing
- massage therapy
- laughing/humor
- ashwagandha
- specific fatty acids (omega-3 NOT OMEGA-6)
- Magnesium supplements after aerobic exercise
Explain how Cushing’s Syndrome occurs and what the characteristics as a result of these diseases are and the treatments.
Cushing’s Syndrome: excess glucocorticoids/cortisol
- causes: tumor, pituitary disorder, wrong medication, ectopic ACTH syndrome
- results: leads to an increase in ACTH and blood sugar (steroid diabetes)
- characteristics: obesity, excess roundness of face, hypertension, hyperglycemia, osteoporosis
- treatment: take something that inhibits cortisol production
Explain how Addison’s Disease occurs, what the characteristics as a result of these diseases are and the treatments.
Addison’s Disease: Opposite of Cushing’s Syndrome - destruction of adrenal cells
- causes: tuberculosis or autoimmune disorders (infection of the adrenal glands)
- results: low cortisol and low aldosterone levels
- characteristics: salt regulation issues, weight loss, hypotension, weakness, decrease in extracellular fluid, increase in MSH leads to pigmentation problems
- treatment: cortisol injections
Explain how Congenital Adrenal Hyperplasia (type 1 and Type 2) occurs, what the characteristics as a result of these diseases are and the treatments.
Congenital Adrenal Hyperplasia (CAH): genetic defect where you have mutations in the specific genes/enzymes which cause issues with the production of cortisol
- Type 1: defect in 21-hydroxylase –> leads to low cortisol levels –> high ACTH due to reduced negative feedback. All intermediates used to make cortisol are now converted to androgens and leads to masculinization of newborn females and early puberty for males
- Type II: defect in 11beta-hydroxylase, leads to hypertensions
- normally ACTH leads to pregnenolone, leading to the production of cortisol, however, if the enzymes required for cortisol synthesis are not present, pregnenolone then becomes dihydroepiandrosterone (DHEA) which become testosterone
Cortisol deficiency and what disease have similar symptoms?
Explain the similarities and why they occur
Addison’s Disease
Both have issues with the pituitary, impaired gluconeogenesis, impaired tolerance to stress, unnatural melanin patching/discoloration. The reason for pigmentation issues is due to an increase in MSH (melanocyte stimulating hormone) which increases melanocyte synthesis. Excess MSH leads to production of more melanocytes in tissues that normally do not have them, leading to darkening in areas that normally aren’t that dark.
In a lot of tissues, testosterone can get reduced to what by what? What does this molecule do and why is the enzyme which produces this often a drug target?
Testosterone can get reduced to 5alpha-dihydrotestosterone (DHT) by 5alpha-reductase. DHT causes male pattern baldness, prostate cancer, and is the “bad testosterone.” It can’t be aromatized and binds to androgen very well and activates the testosterone response a lot better than normal testosterone. Men take 5alpha-reductase inhibitors to prevent the formation of “bad testosterone.”
If you have excess testosterone as a result of congenital adrenal hyperplasia diseases, this can lead to excess buildup of what?
5alpha-dihydrotestosterone
What occurs as a result of 5alpha-reductase deficiency?
It can lead to inhibition of specific secondary male characteristics. If there are issues with the enzyme, children end up not hitting puberty when they are supposed to, and they can lead to the development of opposite genitals to their chromosomes.
What mutations can occur that lead to issues with testosterone and 5alpha-dihydrotestosterone synthesis? What occurs as a result?
5alpha-reductase mutation prevents the development of 5alpha-dihydrotestosterone. There will be issues with testosterone production. Constitutive activation of luteinizing hormone (LH) receptors as a result of mutation can also lead to puberty at a young age. There can also be mutations of the androgen receptors in target tissue and prevents response from androgens.
Abusers of steroids have up to 40x the amount than normal. Do these individuals take just testosterone? What occurs as a result of steroid abuse?
They take a mixture of steroids to affect different parts of the pathway to help increase their testosterone by 40x.
Because there are androgen receptors throughout the entire body, all androgens will act on these receptors and regulate genes throughout the entire body. The overuse can cause
- increased muscle mass
- increased blood pressure
- increased LDL
- decreased HDL
- increased risk of liver and heart damage
- gynocomastia
- increased risk of prostate cancer
- acne
- smaller testicles
- reduced sperm count
- mood swings (roid rage)
