Adrenal Gland 1 Flashcards

1
Q

ADRENAL GLAND OVERVIEW

Located next to the cranial pole of the kidneys Assist with maintaining homeostasis by:

  • Regulating body’s adaptive responses to ?*
  • Maintenance of body balance of:
     ?
     ?
     ?
  • Control of ?

The main hormones of the adrenal gland belong to 2 different families:

? hormones (adrenal cortex)
 Glucocorticoids (cortisol)
 ? (aldosterone)
 ? (sex hormones)

? (adrenal medulla)
 ?
 Norepinephrine
(the other catecholamine is ?)

A

ADRENAL GLAND OVERVIEW

Located next to the cranial pole of the kidneys Assist with maintaining homeostasis by:

  • Regulating body’s adaptive responses to STRESS*
  • Maintenance of body balance of:
     water
     sodium (think of resting membrane potential and action potential)
     potassium
  • Control of blood pressure

The main hormones of the adrenal gland belong to 2 different families:

steroid hormones (adrenal cortex)
 Glucocorticoids (cortisol)
 mineralocorticoids (aldosterone)
 androgens (sex hormones)

Catecholamines (adrenal medulla)
 Epinephrine
 Norepinephrine
(the other catecholamine is dopamine)

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2
Q

LOCATION OF ADRENAL GLAND

located next to the cranial pole of the kidneys

Divisions of the adrenal gland
- Microanatomy organization

CORTEX
- ? in origin
- #? layers (zones)

MEDULLA
- ectodermal in origin (notes: origin of neural and epithelial tissue from ectoderm)

A

LOCATION OF ADRENAL GLAND

located next to the cranial pole of the kidneys

Divisions of the adrenal gland
- Microanatomy organization

CORTEX
- mesodermal in origin
- #3 layers (zones)

MEDULLA
- ectodermal in origin (notes: origin of neural and epithelial tissue from ectoderm)

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3
Q

PIC:

capsule

ADRENAL CORTEX
zona ?,
zona ? (glucocorticoids),
zona ? (androgens),

ADRENAL MEDULLA
adrenal ? (catecholamines)

A

PIC:

capsule

ADRENAL CORTEX (GFRM)
zona glomerulosa (mineralcorticoids)
zona fasciculata (glucocorticoids)
zona reticularis (androgens)

ADRENAL MEDULLA
adrenal medulla (catecholamines)

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4
Q

ADRENAL GLAND HORMONES

CORTEX
* Zona glomerulosa -> ?
* Zona fasciculata -> glucocorticoids
* Zona reticularis -> androgens

MEDULLA
* Adrenal medulla -> catecholamines

A

ADRENAL GLAND HORMONES

CORTEX
* Zona glo”m”erulosa -> mineralocorticoids
* Zona fasciculata -> glucocorticoids
* Zona reticularis -> androgens

MEDULLA
* Adrenal medulla -> catecholamines

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5
Q

HPA - axis

Hypothalamic Pituitary Adrenal axis

Hypothalamus – (CRH: corticotropin-releasing hormone) –> Anterior Pituitary – (ACTH: Adrenocorticotropic Hormone) –> ? ? –> (CORT/cortisol)

when there’s cortisol it sends ? feedback to the hypothalamus and anterior pituitary

PIC:
- arrow going to zona pellucida is thicker so ACTH is much higher to stimulate this and will have lil effect on this

  • hyperkalemia (too much potassium in blood) & angiotensin II -> v thick arrows meaning need a lot of angiotensin II and hyperkalemia to stimulate the release of aldosterone in the glomerular zone (mineralocorticoids)
  • ACTH stimulates release of :

ONLY ADRENAL CORTEX (“adrenocorticotropic” hormone) and not adrenal medulla
aldosterone from: glomerular zone (mineralo-corticoids)
cortisol from: Fascicular zone (glucocorticoids)
androgens from: reticular zone

overproduction of cortisol sends negative feedback to CRH and ACTH

  • CRH from the hypothalamus directly stimulates the release of epinephrine and norepinephrine from the adrenal medulla
  • also epinephrine stimulates ACTH release
    STRESS CAN AFFECT stimulation of CRH and stimulation of ADRENAL MEDULLA
A
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6
Q

MECHANISM OF ACTON OF ACTH (Adrenocorticotropic hormone) ON ADRENOCORTICAL STEROIDOGENESIS

CRH which is produced in the hypothalamus stimulates corticotropin in AP or adenohypophysis to release ACTH which then binds to GPCR receptor and which the help of enzyme AC, ATP is converted from cAMP

and PKA activates diff. enzymes 1, 2, 3, 4

A
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7
Q

STEROID HORMONE SYNTHESIS IMP!!!!(steroidogenesis)

 Derived from ?
* Cholesterol is carried in blood plasma by ?
* Enters the cells via ? mediated endocytosis (recall clathrin)→ then is either used ? or stored as ? form in vesicles

 In the first step, cholesterol is converted to ** ? **
* This first step is common to all ** ? ** hormones
* Occurs in the ?
* This step is regulated by ? (adenohypophysis)
 ? the rate of synthesis of all adrenocortical hormones
 Clinical treatment example: ketoconazole can reversibly inhibit steroidogenesis, blocking several enzymes in different steps of the synthesis pathway → reduces mainly ? levels)

A

STEROID HORMONE SYNTHESIS IMP!!!!(steroidogenesis)

 Derived from cholestrol
* Cholesterol is carried in blood plasma by LDLs
* Enters the cells via receptor-mediated endocytosis (recall clathrin)→ then is either used immediately or stored as ester form in vesicles

 In the first step, cholesterol is converted to ** pregnenolone **
* This first step is common to all ** adrenocortical ** hormones
* Occurs in the mitochondria
* This step is regulated by ACTH (adenohypophysis)
 limits the rate of synthesis of all adrenocortical hormones
 Clinical treatment example: ketoconazole can reversibly inhibit steroidogenesis, blocking several enzymes in different steps of the synthesis pathway → reduces mainly cortisol levels)

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8
Q

STEROIDOGENESIS

Different tissues of the adrenal gland (the different zones) express different ?
 not all processes occur in all cells
i.e., cells of the zona ? don’t have (17ɑ-OH) enzyme

Steroid hormones are ** ? ** stored in vesicles
 When made, steroid hormones are
secreted ? by diffusion across the cell membrane (lipophilic)

A

STEROIDOGENESIS

Different tissues of the adrenal gland (the different zones) express different enzymes
 not all processes occur in all cells
i.e., cells of the zona glomerulosa don’t have (17ɑ-OH) enzyme

Steroid hormones are ** NOT ** stored in vesicles
 When made, steroid hormones are
secreted immediately by diffusion across the cell membrane (lipophilic)

GLOMERULOSA
- mineralcorticoids
cholestrol -> aldosterone

FASCICULATA
- glucocorticoids
to cortisol

RETICULARIS
-androgens (Sex hormones) - innermost
- sex hormones to dihydrotestosterone and estradiol

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9
Q

STEROID HORMONE TRANSPORT

Hydrophobic → carried in plasma in association with ? proteins:

 ?-binding globulin (CBG) or ?
 ?

Cortisol transport
* ?% bound to transcortin
* ?% bound to albumin
* ?% unbound (free state)

Aldosterone transport
* ?% bound to transcortin
* ?% bound to albumin
* ?% unbound (free state)

(need to be free before they enter the target cell)

FREE CORTISOL + BOUND CORTISOL = TOTAL CORTISOL

A

STEROID HORMONE TRANSPORT

Hydrophobic → carried in plasma in association with transport proteins:

 corticosteroid-binding globulin (CBG) or transcortin
 albumin

Cortisol transport
* 75% bound to transcortin
* 15% bound to albumin
* 10% unbound (free state)

Aldosterone transport
* 10% bound to transcortin
* 50% bound to albumin
* 40% unbound (free state)

(need to be free before they enter the target cell)

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10
Q

HORMONE RECEPTOR INTERACTION

Steroid hormones bind to ? receptors (as they have no trouble crossing the hydrophobic membrane)

 steroid receptor superfamily
* steroid receptors can be located:
 ?
 ?

  • cytoplasmic receptors translocate to the ? after ? binding
  • Androgen hormones can bind to ** cell surface ? ** (GPCR, ligand-gated channels and others) triggering a ** ? cellular response **

HORMONES BIND TO THEIR RESPECTIVE INTRACELLULAR receptor ALTERING THE ABILITY OF THESE PROTEINS TO CONTROL THE ? OF SPECIFIC GENES

A

HORMONE RECEPTOR INTERACTION

Steroid hormones bind to INTRACELLULAR receptors (as they have no trouble crossing the hydrophobic membrane)

 steroid receptor superfamily
* steroid receptors can be located:
 cytoplasm
 nucleus

  • cytoplasmic receptors translocate to the nucleus after hormone binding
  • Androgen hormones can bind to ** cell surface receptor ** (GPCR, ligand-gated channels and others) triggering a ** RAPID cellular response **

HORMONES BIND TO THEIR RESPECTIVE INTRACELLULAR receptor ALTERING THE ABILITY OF THESE PROTEINS TO CONTROL THE transcription OF SPECIFIC GENES
- complex binds to sites on chromatin, activating mRNA transcription

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11
Q
  1. Most hydrophobic steroids are bound to plasma protein ?. Only ? hormones can diffuse into the target cell
  2. Steroid hormone receptors are in the ? or ?

2a. some steroid hormones also bind to membrane receptors that use second ? systems to create ? cellular responses

  1. the receptor-hormone complex binds to ? and activates or represses one or more ?
  2. activated genes create new ? that moves back to the ?
  3. translation produces new ? for cell processes
A
  1. Most hydrophobic steroids are bound to plasma protein carriers. Only unbound hormones can diffuse into the target cell

(note: 1 in pic is coming from which type of blood vessels? = CAPILLARIES)

  1. Steroid hormone receptors are in the cytoplasm or nucleus

2a. some steroid hormones also bind to membrane receptors that use second messenger systems to create RAPID cellular responses

  1. the receptor-hormone complex binds to DNA and activates or represses one or more genes
  2. activated genes create new mRNA that moves back to the cytoplasm
  3. translation produces new proteins for cell processes
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12
Q

STEROID HORMONE METABOLISM AND ELIMINATION

Metabolism involves mainly the ? (organ)
 ? of the hormones for excretion
 Conjugation to ? and ?
* reduces biological ?
* become ?-soluble for passage in the urine

clearancy half-life
-> cortisol: #? mins
-> aldosterone: #? mins

A

STEROID HORMONE METABOLISM AND ELIMINATION

Metabolism involves mainly the liver (organ)
 modification of the hormones for excretion
 Conjugation to sulfates and glucuronides
* reduces biological potency
* become water-soluble for passage in the urine

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13
Q

Zona glomerulosa - mineralocorticoids

A
  1. zona glomurulosa (mineralcorticoids)
  2. zona fasciculata (glucocorticoids)
  3. zona reticularis (androgens)
  4. ADRENAL medulla (and NOT zona!!!)
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14
Q

ZONA GLOMERULOSA - MINERALOCORTICOIDS

Mineralocorticoids are corticosteroids that influence ** ? and ? balance **
** ? and ? balance (mainly Na+ K+ and water)
 ? is the primary mineralocorticoid **

What stimulates aldosterone synthesis and secretion?
 ** ? ** (high or low? BP)
 low [Na+]
(above 2 involved in RAAS: renin-? system)
 high [K+]

* ACTH has a lot of little? effect in aldosterone synthesis.*
There are few receptors for ?
located in the cells of zona ?

A

ZONA GLOMERULOSA - MINERALOCORTICOIDS

Mineralocorticoids are corticosteroids that influence ** salt and water balance **
** electrolytes and fluid balance (mainly Na+ K+ and water)
 ALDOSTERONE is the primary mineralocorticoid **

What stimulates aldosterone synthesis and secretion?
 ** HYPOTENSION ** (low BP)
 low [Na+]
(above 2 involved in RAAS: renin-angiotensin system)
 high [K+]

* ACTH has a little effect in aldosterone synthesis.*
There are few receptors for ACTH
located in the cells of zona glomerulosa

(zona fasciculata (glucocorticoids) for production of aldosterone)

PIC:
- angiotensinogen stimulated by RENIN to get converted into angiotensin I which then gets converted into (w the help of ACE angiotensin-converting enzyme in lungs)

angiotensin II which stimulates the adrenal cortex to secrete aldosterone

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15
Q

ALDOSTERONE REGULATION

Production of aldosterone is mainly regulated by the Renin-angiotensin-? system (RAAS)

STIMULI for renin secretion:
 low [Na+] in renal filtrate
-> detected by cells of ? densa

 Reduced ** ? ? ** in the kidney detected by baroreceptors in the afferent arteriole

 ** ? stimulation ** of the juxtaglomerular apparatus via ** β?# ? **

A

ALDOSTERONE REGULATION

Production of aldosterone is mainly regulated by the Renin-angiotensin-aldosterone system (RAAS)

STIMULI for renin secretion:
 low [Na+] in renal filtrate
-> detected by cells of macula densa

 Reduced ** BP ** in the kidney detected by baroreceptors in the afferent arteriole

 ** sympathetic stimulation ** of the juxtaglomerular apparatus via ** β1 adrenoreceptors **

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16
Q

RENIN - ANGIOTENSIN - ALDOSTERONE SYSTEM

  1. angiotensin release from liver
  2. angiotensinogen reaction: angiotensin I
  3. angiotensin I then go to the lungs and lungs have ACE (surface of pulmonary and renal endothelium)
  4. so ACE converts angiotensin I to angiotensin II
  5. angiotensin II stimulates:
    a. sympathetic activity
    b. tubular Na+ Cl- reabsorption and K+ excretion. H2O retention
    c. stimulates adrenal gland: cortex to secrete aldosterone which in turn stimulates b.
    d. arteriolar vasoconstriction, increase in BP
    e. stimulates ADH secretion from the neurohypophysis (made in the hypothalamus)
    -> ADH secretion stimulates collecting duct: H2O reabsorption

5 a-e: water and salt retention. Effective circulating volume increases. Perfusion of the juxtaglomerular apparatus increases -> ** high Na conc. in filtrate, high water absorption, high BP — negative feedback low Na conc. in filtrate; low BP ** –> to stop secreting renin from kidney

A
17
Q

ALDOSTERONE REGULATION

** ? ** is another major regulatory factor for mineralocorticoid secretion
** An increase in [K+] directly stimulates zona ? to secrete ? ** → (independent of RAAS)

A

ALDOSTERONE REGULATION

** POTASSIUM ** is another major regulatory factor for mineralocorticoid secretion
** An increase in [K+] directly stimulates zona glomerulosa to secrete aldosterone ** → (independent of RAAS)

18
Q

ALDOSTERONE ACTION ON KIDNEY’S DISTAL TUBULES

ALDOSTERONE acts on ? tubules in the ?:
 ** Active ? of sodium (Na+) **
* increasing activity of epithelial ? channels
* synthesis of ?-? pump (Na+/K+-ATPase)

 ** Active secretion of ? (K+) **
* Synthesis of potassium channels

** Active ? of protons H+
 ? ? of water (water flows with Na+) **

A

ALDOSTERONE ACTION ON KIDNEY’S DISTAL TUBULES

ALDOSTERONE acts on distal tubules in the kidneys:
 ** Active resorption of sodium (Na+) **
* increasing activity of epithelial sodium channels
* synthesis of sodium-potassium pump (Na+/K+-ATPase)

 ** Active secretion of potassium (K+) **
* Synthesis of potassium channels

(need to get rid of unimp. potassium)

 Active secretion of protons H+
 passive reabsorption of water (water flows with Na+)

19
Q

Aldosterone action on kidney’s distal tubules

  1. aldosterone combines w a ? receptor (note: aldosterone released from which type of blood vessel?)
  2. hormone-receptor complex initiates ? in the nucleus
  3. new ? channels and ? are made
  4. aldosterone-induced proteins modify existing ?
  5. result is increased Na+ ? and K+ ?
A

Aldosterone action on kidney’s distal tubules

  1. aldosterone combines w a cytoplasmic receptor (note: aldosterone released from which type of blood vessel? = CAPILLARIES (perfusion occurs here))
  2. hormone-receptor complex initiates transcription in the nucleus
  3. new protein channels and pumps are made
  4. aldosterone-induced proteins modify existing proteins
  5. result is increased Na+ reabsorption and K+ secretion

pic:
3. translation and protein synthesis occur in cytoplasm from where new channels and new pumps are made

  1. proteins modulate existing channels and pumps -> ATP (na K atpase pump?) (aldoesterone icnreases this: ARROW TO ATIP)

note: active step here (atp part) and passive step on the left (5) due to gradient difference concentration

(Na is reabsorbed and taken back into the blood and K is excreted into urine )

20
Q

ALDOSTERONE ACTION ON KIDNEY’S DISTAL TUBULES

sodium reabsorption (filtrate -> blood): ** ? process **

potassium secretion (blood -> filtrate): ** ? process **

A

ALDOSTERONE ACTION ON KIDNEY’S DISTAL TUBULES

sodium reabsorption (filtrate -> blood): ** ACTIVE process **

potassium secretion (blood -> filtrate): ** ACTIVE process **