Adrenal Gland Physiology Flashcards Preview

DEMS: Unit III > Adrenal Gland Physiology > Flashcards

Flashcards in Adrenal Gland Physiology Deck (26)
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1
Q

Key Steps in steroid hormone biosynthesis

A
  • release of cholesterol from lipid droplets inside the cell by removing esters
  • Subsequent steps in steroid hormone synthesis occur within either the mitochondria or endoplasmic reticulum.
  • The rate-limiting step requires mitochondrial enzymes - the cytochrome P-450 enzymes or 20, 22 desmolase.
  • Pregnenolone is the product of this reaction. This rxn occurs throughout the cortex.
  • each pathway used different biosynthetic enzymes. .
2
Q

Transport of glucocorticoids in plasma

A
  • Cortisol circulates primarily (90%) bound to proteins.
    • Of the 90% that is bound, 75% is bound to cortisol binding globulin (CBG) and 15% is bound to albumin.
  • 10% circulates in a free form. Remember, free hormone is the amount that matters physiologically and is regulated.
3
Q

General/overall actions of cortisol

A
  • Major stress hormone in the body, necessary for life. Prolonged stress is detrimental to health.
  • Formed in the zona fasiculata
  • Overall: ↓ insulin actions → ↑ serum glucose, ↑ FFA from adipose tissue
4
Q

Cortisol action @ liver

A

↑ gluconeogenesis → ↑ serum glucose

5
Q

Cortisol action @ adipose and muscle tissue

A
  • Adipose Tissue:
    • Activates hormone sensitive lipase → ↑ serum FFA
    • Results in fat deposition on trunk, abdomen, face; mobilization of fat from extremities
  • Muscle: proteolysis makes more amino acids available for gluconeogenisis
6
Q

Cortisol effects on water balance

A

Inhibits ADH → ↑ water excretion (inverse stimulation of ADH secretion)

7
Q

Cortisol actions @ stomach

A

Increased gastric acid secretion

8
Q

Cortisol actions @ adrenal cortex

A
  • Paracrine effect: Increases conversion of NE → Epi
  • Cortisol is permissive of epinephrine; epi is much more active in presence of cortisol
9
Q

Cortisol actions @ heart

A
  • ↑ cortisol → ↑ RBC production → Polycythemia
  • Too little cortisol → ↓ RBC production → Anemia
  • ↑ β adrenergic receptor synthesis in target tissues, so for heart, ↑ HR, contractility, etc.
10
Q

Cortisol actions @ brain

A

depression and psychotic symptoms result from changes in cortisol levels, mechanism unknown

11
Q

Consequences of excess cortisol

A
  • Skin: thinning by ↓ fibroblast proliferation
  • Capillaries: fragility → bruising
  • CV: polycythemia
  • Bone: ↓ calcium absorption from gut and interferes with bone formation → fractures and osteoporosis
  • Cortisol is antagonist of Vitamin D
  • Anti-inflammatory effects: influences prostaglandins, cytokines, migration, etc. Inhibits phospholipase A2
  • Immunosuppressant: ↓ T-cell proliferation, ↓ T-cell activation
12
Q

Mechanism of ACTH release

A
  • Parvocellular (small) neurons (Supraoptic + Paraventricular) from the hypothalamus secrete CRH into H-P portal system
  • CRH binds to receptors on corticotrophs in the pituitary thereby activating adenylate cyclase
  • Ca2+ influx which stimulates release of ACTH.
  • POMC gene transcription is also activated.
13
Q

Regulations of release of ACTH

A
  • Negative feedback: Plasma free cortisol feeds back on the hypothalamus and the pituitary to inhibit CRH and ACTH secretion.
  • Stimulation of release: Stress of various forms stimulates secretion of CRH and thus ACTH and cortisol.
    • Stress can be physical in nature such as pain, trauma or cold exposure.
    • Emotional stress and specific chemicals are also effective stimulants.
14
Q

ACTH actions @ adrenal gland (general)

A

ACTH interacts with receptors on the cells of the Zona fasciculata and reticularis to promote secretion of cortisol. ACTH has several actions, which lead to increased cortisol secretion.

15
Q

Actions of ACTH @ adrenal gland ==> cortisol secretion

A
  • In the cortex, ACTH → ↑ cAMP levels (via Gs protein) → ↑ the rate of synthesis of pregnenolone.
  • ↑ All cellular numbers in adrenal cortex, and ↑ in all enzymes
    • ACTH mainly ==> cortisol, so mineralcorticoids still secreted if ACTH disrupted
  • ↑ LDL uptake
  • ↑ Hydrolysis of stored cholesterol esters and transport of cholesterol into mitochondria.
  • Adrenal androgens generally vary with the secretion of cortisol and appear to be stimulated by ACTH.
16
Q

Characteristics of chromaffin cells (general)

A
  • medulla is essentially a specialized sympathetic ganglion
  • The cells of medulla are called adrenal chromaffin cells because they bind chromium dyes
  • Chromaffin cells make epinephrine.
17
Q

Mechanism of epinephrine release from medullary chromaffin cells

A
  • sympathetic cholinergic preganglionic fibers that release ACh @ nAChRs on chromaffin cells
  • ==> cation flow (mostly Na+ and some Ca2+) into the chromaffin cell ==> depolarization ==> calcium influx through voltage-gated calcium channels
  • Changes in intracellular calcium lead to release of catecholamines via calcium-dependent exocytosis.
  • The main hormone released is epinephrine, and to a lesser extent, norepinephrine (NE).
  • This is a rapid mechanism. There is a slow response as well, mediated by muscarinic receptors.
18
Q

Rate limiting step in formation of NE and Epinephrine

A

Rate limiting step is formation of NE and Epi via tyrosine hydroxylase in the cytosol of chromaffin cells.

19
Q

General actions of epinephrine

A
  • acts through GPCRs
  • ↑ Glycogenolysis
  • Urinary - relaxes detrusor at β2, closes sphincter and contracts trigone at α1
  • ↓ Glucose utilization
20
Q

Epinephrine actions @ beta1 receptors

A
  • ↑ Cardiac contractility
  • ↑ Heart rate
  • ↑ Conduction velocity
21
Q

Epinephrine actiosn @ beta2 receptors

A
  • ↑ Gluconeogenesis
  • ↑ Lipolysis
  • ↑ Insulin secretion at pancreatic β cells
  • ↑ Glucagon secretion
  • ↑ Muscle K+ uptake
  • ↑ Arteriolar dilation and ↓ BP in skeletal muscle
  • ↑ Muscle relaxation
  • ↑ Bronchodilation
22
Q

Epinephrine actions @ beta3 receptors

A

↑ Lipolysis via Hormone sensitive lipase

23
Q

Mechanism of action of epinephrine @ alpha1 & alpha2 receptors

A
  • α1 → Gq → PLC → PIP2
    • → IP3 → Ca2+ OR
    • → DAG → PKC
  • α2 → Gi → ↓ cAMP
24
Q

Mechanism of action of epinephrine @ beta receptors

A
  • β 1, 2, 3 → Gs → ↑ cAMP
25
Q

Epinephrine actions @ alpha vs. beta receptos

A
  • Epi works more at β receptors than at α receptors. NE works better at α.
  • Net effect at cells depends on ratio of β to α receptors as they antagonize eachother as seen in pathways above.
  • @ Pancreatic β cells the primary receptor type is α adrenergic (stimulation of which, by Epi, is inhibitory).
    • Prolonged epinephrine release, like during exercise, can uncouple the insulin/glucose.
    • epi doesnt cause increased insulin action during exercise.
  • Epinephrine is one of strongest stimulators of hormone sensitive lipase.
    • Provides with burst of FFA as source of energy.
26
Q

Body’s integrated response to stress

A
  • 3 main responses to stress in the brain:
  • NE in brain produces rapid arousal.
  • CRH activates cortisol,
  • And the sympathetic system creates epinephrine.