Stress And Metabolism: Cortisol

Question 1

Anatomical zones of adrenal cortex

Answer 1

. Zona glomerulosa: outermost zone lying immediately beneath capsule of gland
. Zona fasciculata: middle zone and largest portions f cortex
. Zona reticularis: innermost zone

Question 2

Glucocorticoids

Answer 2

. Cortisol is most important
. Corticosterone can be important under certain circumstances
. Produced in zona fasciculate
. Essential to life CN of their effects on carb and protein metabolism

Question 3

Mineralcorticoids

Answer 3

. Aldosterone produced only in zona glomerulosa

. Vital to maintain Na and K balance and ECF volume

Question 4

Sex steroids

Answer 4

. Androgens and estrogens

. Produced only in zona reticularis

Question 5

Synthesis of adrenocortical hormones

Answer 5

. Cholesterol transported from cytoplasm to mitochondrial matrix through StAR protein
. Cholesterol hydroxylated and side-chain cleaved by cytochrome P-450 enzymes to form pregnenolone (rate-limiting step in cortisol synthesis)
. Specific enzymes then take pregnenolone and turn it into whatever steroid is needed

Question 6

Where cholesterol comes from?

Answer 6

In LDL

. Stored in endocrine cells as an ester

Question 7

How is rate of steroid hormone secretion controlled?

Answer 7

. Regulation of synthesis
. Hormones diffuse out of adrenal cells and bind to circulating proteins in plasma
. Cortisol is 95% protein bound (75% corticosteroid-binding globulin, 20% to albumin)
. 5% cortisol exits free in plasma
. Cortisol diffuses into target cell and binds to cytosolic receptor
. Complex then moves into clues to stimulate protein synthesis and altering enzymatic rxns and cell function

Question 8

Control of cortisol transport proteins

Answer 8

. Estrogens inc. hepatic synthesis of CBG that inc. protein bound cortisol altering the total plasma cortisol conc.

Question 9

Cortisol effects on protein

Answer 9

. Inc. plasma AA conc.
. Inc. degradation of mm., CT
. Dec. insulin-stimulated AA uptake
. Inc. conversion of AA into glucose (gluconeogenesis)

Question 10

Cortisol effects on carbs

Answer 10

. Inc. plasma glucose conc.
. Inc. glucose production by liver
. Inc. catabolism of tissue protein for glucose production
. Dec. insulin-stimulated glucose uptake in mm. And adipose (inhibition of GLUT-4 insertion)
. Inc. glucagon sec.
. Inc. E synthesis
. Inc. glycogen synthesis

Question 11

Cortisol effects on lipids

Answer 11

. Inc. plasma FA conc.
. Inc. lipolysis in tissues
. Permissive for lipolysis caused by E (via PMNT) and GH (glucose-sparing effect)
. Permissive for action of NE, E, ADH, and G

Question 12

Permissive effects of cortisol on cardiovascular system

Answer 12

. Catecholamines and angiotensin require permissive amts of cortisol to stimulate contraction of vascular smooth m. And cardiac m. To maintain arterial bp
. Permissive amts cortisol needed for normal capillary permeability to maintain vascular BV
. Results from expressing more adrenergic receptors and voltage-gated Ca channels

Question 13

Permissive effects of cortisol on metabolism and growth

Answer 13

. Required for E and GH release and metabolic actions

Question 14

Supramaximal effects of cortisol

Answer 14

. Suppress inflammation and cell-mediated immunity
. Inhibits synthesis of prostaglandins and leukotrienes
. Excessive breakdown of endogenous functional protein (thinning of skin, mm. Wasting, bone breakdown)
. Endogenous ACTH secretion is suppressed
. Hyperglycemia
. High FA content in plasma

Question 15

Metabolism of adrenocortical hormones

Answer 15

. Metabolized slowly due to extensive protein-binding in plasma
. Half-life: 70-90 min
. Metabolized in liver where it is converted to water-soluble molecule to facilitate excretion
. Metabolism slower in rants and the aged
. Inc. in hyperthyroidism and dec. in hypothyroidism

Question 16

How cortisol secretion is stimulated

Answer 16

. Hypothalamic corticotropin-releasing hormone (CRH) stimulates cleavage of precursor pro-opiomelancortin (POMC) producing ACTH and beta-endorphins from fragment beta-LPH
. Major stimulus: physio or psych stress
. ACTH stimulates cortisol synthesis via stimulating LDL uptake, hydrolyzing esters and stimulating cholesterol transport into mitochondria, and promoting binding of cholesterol to cytochrome P-450 initiating pregnenolone formation

Question 17

Chronic ACTH elevation

Answer 17

. Hypertrophy of adrenal tissue

. Elevation in free cortisol conc. In plasma

Question 18

Negative feedback loop w/ cortisol

Answer 18

. High cortisol conc. Depresses ACTH and CRH release

Question 19

Pattern of CRH-ACTH-cortisol pathway

Answer 19

. Diurnal
. Secretion greatest during early morning hours and minimal late at night
. Related to sleep and food-activity cycles

Question 20

Magnitude of cortisol secretion is proportional to ___

Answer 20

. Intensity of stressful stimulus
. Acute stress: greatest cortisol response
. Adaptation occurs to chronic stress
. Cortisol can override the neg. feedback effects from hypothalamus and pituitary if stress stimulus is large enough

Question 21

Hormone levels in addision’s

Answer 21

. Low cortisol

. Inc. CRH and ACTH

Question 22

Hormone levels from pituitary adenoma

Answer 22

. Inc. ACTH and cortisol

. Dec. CRH

Question 23

Hormone levels from adrenal adenoma/carcinoma

Answer 23

. High cortisol

. Low ACTH and CRH

Question 24

Hormone levels from ectopic ACTH production from lung carcinoma

Answer 24

. Inc. ACTH overall, dec. ACTH from pituitary
. Dec. CRH
. Inc. cortisol

Question 25

Hormone levels from ectopic CRH production

Answer 25

. Inc. CRH from ectopic tumor, dec. CRH from hypothalamus

. Inc. ACTH and cortisol

Question 26

Hormone levels in iatrogenic Cushing’s syndrome

Answer 26

. Inc. cortisol from meds
. Dec. cortisol from atrophied adrenal cortex
. Dec. CRH and ACTH

Question 27

Termination of exogenous steroid meds

Answer 27

. ACTH production suppressed w/ high cortisol meds
. Atrophy of adrenal cortex can occur
. Dosage of cortisol must be gradually dec. to allow endogenous cortisol and ACTH to resume their normal interaction