Stress And Metabolism: Cortisol Flashcards
Anatomical zones of adrenal cortex
. Zona glomerulosa: outermost zone lying immediately beneath capsule of gland
. Zona fasciculata: middle zone and largest portions f cortex
. Zona reticularis: innermost zone
Glucocorticoids
. 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
Mineralcorticoids
. Aldosterone produced only in zona glomerulosa
. Vital to maintain Na and K balance and ECF volume
Sex steroids
. Androgens and estrogens
. Produced only in zona reticularis
Synthesis of adrenocortical hormones
. 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
Where cholesterol comes from?
In LDL
. Stored in endocrine cells as an ester
How is rate of steroid hormone secretion controlled?
. 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
Control of cortisol transport proteins
. Estrogens inc. hepatic synthesis of CBG that inc. protein bound cortisol altering the total plasma cortisol conc.
Cortisol effects on protein
. Inc. plasma AA conc.
. Inc. degradation of mm., CT
. Dec. insulin-stimulated AA uptake
. Inc. conversion of AA into glucose (gluconeogenesis)
Cortisol effects on carbs
. 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
Cortisol effects on lipids
. 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
Permissive effects of cortisol on cardiovascular system
. 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
Permissive effects of cortisol on metabolism and growth
. Required for E and GH release and metabolic actions
Supramaximal effects of cortisol
. 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
Metabolism of adrenocortical hormones
. 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
How cortisol secretion is stimulated
. 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
Chronic ACTH elevation
. Hypertrophy of adrenal tissue
. Elevation in free cortisol conc. In plasma
Negative feedback loop w/ cortisol
. High cortisol conc. Depresses ACTH and CRH release
Pattern of CRH-ACTH-cortisol pathway
. Diurnal
. Secretion greatest during early morning hours and minimal late at night
. Related to sleep and food-activity cycles
Magnitude of cortisol secretion is proportional to ___
. 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
Hormone levels in addision’s
. Low cortisol
. Inc. CRH and ACTH
Hormone levels from pituitary adenoma
. Inc. ACTH and cortisol
. Dec. CRH
Hormone levels from adrenal adenoma/carcinoma
. High cortisol
. Low ACTH and CRH
Hormone levels from ectopic ACTH production from lung carcinoma
. Inc. ACTH overall, dec. ACTH from pituitary
. Dec. CRH
. Inc. cortisol
