Lecture 32 - Adrenocorticosteroids

Question 1

the adrenal gland is divided into two main structures:

Answer 1

the cortex and medulla

Question 2

the inner part of the adrenal gland

Answer 2

medulla

Question 3

which hormones are secreted by the adrenal medulla?

Answer 3

adrenaline and noradrenaline

Question 4

the outer part of the adrenal gland

Answer 4

cortex

Question 5

what are the three “zones” of the adrenal cortex?

Answer 5

• zona glomerulosa
• zona fasciculata
• zona reticularis

Question 6

what is the main function of the adrenal cortex?

Answer 6

secretes steroid hormones

Question 7

what hormones are secreted by the zona glomerulosa?

Answer 7

mineralocorticoids

Question 8

what is the purpose of mineralocorticoids?

Answer 8

salt balance –> works on the nephron of the kidney to control the amount of Na+ that is resorbed or excreted

Question 9

what hormones are secreted by the zona fasciculata?

Answer 9

glucocorticoids

Question 10

what is the purpose of glucocorticoids?

Answer 10

functions in metabolic and immune response

Question 11

what hormones are secreted by the zona reticularis?

Answer 11

androgens

Question 12

what is the purpose of androgens?

Answer 12

precursors for strong androgens (testosterone) and estrogens

Question 13

steroid hormones are metabolites of cholesterol that bind to ______ with high specificity

Answer 13

intracellular receptors

Question 14

can steroid hormones be stored like peptide hormones?

Answer 14

no, they are rapidly synthesized when required

Question 15

a network of endocrine organs that regulate homeostasis by integrating signals from both the central nervous systems and peripheral tissues

Answer 15

the hypothalamic-pituitary-adrenal (HPA) axis

Question 16

ACTH is controlled by _____from the hypothalamus

Answer 16

corticotropin-release hormone (CRH)

Question 17

when does ACTH stimulate steroid production?

Answer 17

after meals, and just before waking (circadian rhythm)

Question 18

stimulates cortisol synthesis and release

Answer 18

ACTH

Question 19

list the major steps in the hypothalamic-pituitary-adrenal (HPA) axis

Answer 19

1) stimulation of the hypothalamus to produce cortiocotropin releasing hormone (CRH)
2) CRH acts on the anterior pituitary to release ACTH
3) ACTH acts on the adrenal cortex to secrete cortisol

Question 20

a cortisol-mediated _____ is fundamental for termination of the HPA axis response to stress

Answer 20

-ve feedback loop

Question 21

how are glucocorticoids released in non-stressed (or basal) conditions?

Answer 21

released rhythmically with both a circadian and ultradian (pulsatile) pattern

Question 22

cortisol secretion is characterized by an:

Answer 22

ultradian rhythm (high frequency pulsatile secretion)

Question 23

what is the primary role of the renin-angiotensin-aldosterone system (RAAS)?

Answer 23

to control blood pressure and fluid balance in the body

Question 24

metabolites of cholesterol that bind to intracellular receptors with high specificity

Answer 24

steroid hormones

Question 25

how are steroid hormones carried through the bloodstream?

Answer 25

binds to corticosteroid CBG

Question 26

do steroid hormones enter their target tissues as free steroids or are they still bound to CBG?

Answer 26

enter as free steroids

Question 27

what happens when a steroid hormone binds with its target receptor?

Answer 27

1) binding of the hormone displaces heat shock proteins (Hsp) 2) the activated steroid-receptor dimer is translocated to the nucleus 3) the dimer binds to the glucocorticoid receptor element (GRE) in the DNA promotor region 4) gene transcription and translation is stimulated --> biological response

Question 28

endogenous glucocorticoids activate both:

Answer 28

glucocorticoid receptors (GR) and mineralocorticoid receptors (MR)

Question 29

synthetic glucocorticoids have different affinities for:

Answer 29

glucocorticoid receptors (GR) and mineralocorticoid receptors (MR)

Question 30

which is the more potent activator of the glucocorticoid receptors (GRs): synthetic glucocorticoids or endogenous glucocorticoids?

Answer 30

synthetic glucocorticoids

Question 31

cortisol circulates as its inactive form and is converted to its active form by _____ in most tissues

Answer 31

11-beta-hydroxysteroid dehydrogenase 1 (11-beta-HSD1)

Question 32

why is it that cortisol has such when effects on the kidneys, even though it activates the mineralocorticoid receptors (MRs)?

Answer 32

kidney cells (mineralocorticoid targets) express the enzyme 11-beta-hydroxysteroid dehydrogenase II (11-beta-HSDII) that inactivates cortisol

Question 33

what happens when the 11-beta-HSDII enzyme is inhibited (known as the 'licorice overdose')?

Answer 33

cortisol binds to the mineralocorticoid receptors (MRs), which mistake it for aldosterone, leading to an inappropriate aldosterone-like effect (can cause high blood pressure)

Question 34

a genetic disease arising from mutations in the 11-beta-HSDII enzyme

Answer 34

apparent mineralocorticoid excess

Question 35

a synthetic glucocorticoid that has both anti-inflammatory and immunomodulating properties

Answer 35

prednisone

Question 36

orally administered prednisone undergoes significant first-pass metabolism in the liver to become:

Answer 36

prednisolone

Question 37

is prednisone effective when administered topically?

Answer 37

no

Question 38

is prednisolone effective when administered topically?

Answer 38

yes

Question 39

a glucocorticoid that provides strong negative feedback to the hypothalamus and pituitary, decreasing the secretion of CRH and ACTH, resulting in suppression of endogenous cortisol

Answer 39

dexamethasone

Question 40

where does the name "glucocorticoid" come from?

Answer 40

their profound effects on glucose levels

Question 41

how does cortisol impact the liver?

Answer 41

- promotes gluconeogenesis - increases glycogen storage

Question 42

how does cortisol impact the skeletal muscle?

Answer 42

- inhibits glucose uptake and oxidation - reduces glycogen storage - increases protein degredation (to provide a.a. as precursors for gluceoneogenesis)

Question 43

how does cortisol impact the white adipose tissue (WAT)?

Answer 43

- inhibits glucose uptake and oxidation - increases lipolysis (provides glycerol as precursors for gluconeogenesis)

Question 44

how does cortisol impact the pancreas?

Answer 44

- inhibits insulin secretion - increases glucagon secretion - induces beta-cell hyperplasia

Question 45

the effects of cortisol on the liver, skeletal muscle, and adipose tissue are critical for:

Answer 45

metabolic adaptations during stress (ex: fasting/starvation) when plasma glucose needs to be preserved

Question 46

a hormone secreted from the beta cells of the pancreas

Answer 46

insulin

Question 47

what does insulin do?

Answer 47

inhibits hepatic gluconeogenesis and promotes uptake of glucose into the tissues

Question 48

how do glucocorticoids impact insulin?

Answer 48

antagonizes insulin actions by inibiting glucose uptake in muscle and adipose tissue

Question 49

true or false: chronic glucocorticoid use alters body composition and results in hyperglycemia and metabolic syndrom

Answer 49

true

Question 50

persistant gluconeogenesis and glucose production directly cause hyperglycemia and lead to:

Answer 50

insulin resistance

Question 51

how do glucocorticoids regulate inflammation?

Answer 51

inhibit arachadonic acid generation and inhibit prostanoids (prostaglandins and thromboxanes)

Question 52

plays an important role in the metabolism of arachadonic acid to various prostanoids

Answer 52

COX-2

Question 53

true or false: glucocorticoid regulation of COX-2 involves direct receptor antagonism

Answer 53

false, glococorticoids suppress the transcription of the COX-2 gene

Question 54

glucocorticoids can induce the production of _____, a group of proteins which inhibit phospholipase A2

Answer 54

lipocortins (annexins)

Question 55

annexin A-I plays an important anti-inflammatory role for two important reasons:

Answer 55

1) direct effects on leukocytes inhibits their tissue infiltration 2) suppression of phospholipase 2 activity (prevents arachadonic acid generation)

Question 56

a disease characterized by the inability of the adrenal cortex to produce a sufficient amounts of glucocorticoids and mineralocorticoids

Answer 56

Addison's disease

Question 57

- fatigue - anorexia - nausea - dizziness - weight loss - salt-craving - hyperpigmentation these are all symptoms of:

Answer 57

Addison's disease

Question 58

how is Addison's disease treated?

Answer 58

with glucocorticoid/mineralocorticoid supplementation (hydrocortisone/cortisol)

Question 59

disease caused by hypercortisolemia, leading to the occurence of characteristic clinical symptoms (cardiac disease, osteoporosis, infertility, sexual dysfunction, obesity, infection, myopathy, liver steatosis, vascular disease, and neuropsychiatric disorders)

Answer 59

Cushing's syndrome

Question 60

what are the three main causes of Cushing's syndrome?

Answer 60

- adrenal tumors (increase cortisol production) - pituitary tumor (increase ACTH production) - drug induced (long term tratment with high doses of glucocorticoids)

Question 61

how is Cushings syndrome treated?

Answer 61

depends on cause and may include surgery, radiation, chemotherapy, cortisol reducing medicines, or reduction of glucocorticoid dosage (if cause is drug induced)