Adrenal Gland 1 Flashcards
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 ?)
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)
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)
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)
PIC:
capsule
ADRENAL CORTEX
zona ?,
zona ? (glucocorticoids),
zona ? (androgens),
ADRENAL MEDULLA
adrenal ? (catecholamines)
PIC:
capsule
ADRENAL CORTEX (GFRM)
zona glomerulosa (mineralcorticoids)
zona fasciculata (glucocorticoids)
zona reticularis (androgens)
ADRENAL MEDULLA
adrenal medulla (catecholamines)
ADRENAL GLAND HORMONES
CORTEX
* Zona glomerulosa -> ?
* Zona fasciculata -> glucocorticoids
* Zona reticularis -> androgens
MEDULLA
* Adrenal medulla -> catecholamines
ADRENAL GLAND HORMONES
CORTEX
* Zona glo”m”erulosa -> mineralocorticoids
* Zona fasciculata -> glucocorticoids
* Zona reticularis -> androgens
MEDULLA
* Adrenal medulla -> catecholamines
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
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
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)
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)
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)
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
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
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)
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
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
- Most hydrophobic steroids are bound to plasma protein ?. Only ? hormones can diffuse into the target cell
- Steroid hormone receptors are in the ? or ?
2a. some steroid hormones also bind to membrane receptors that use second ? systems to create ? cellular responses
- the receptor-hormone complex binds to ? and activates or represses one or more ?
- activated genes create new ? that moves back to the ?
- translation produces new ? for cell processes
- 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)
- 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
- the receptor-hormone complex binds to DNA and activates or represses one or more genes
- activated genes create new mRNA that moves back to the cytoplasm
- translation produces new proteins for cell processes
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
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
Zona glomerulosa - mineralocorticoids
- zona glomurulosa (mineralcorticoids)
- zona fasciculata (glucocorticoids)
- zona reticularis (androgens)
- ADRENAL medulla (and NOT zona!!!)
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 ?
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
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?# ? **
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 **
RENIN - ANGIOTENSIN - ALDOSTERONE SYSTEM
- angiotensin release from liver
- angiotensinogen reaction: angiotensin I
- angiotensin I then go to the lungs and lungs have ACE (surface of pulmonary and renal endothelium)
- so ACE converts angiotensin I to angiotensin II
- 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
ALDOSTERONE ACTION ON KIDNEY’S DISTAL TUBULES
sodium reabsorption (filtrate -> blood): ** ? process **
potassium secretion (blood -> filtrate): ** ? process **
ALDOSTERONE ACTION ON KIDNEY’S DISTAL TUBULES
sodium reabsorption (filtrate -> blood): ** ACTIVE process **
potassium secretion (blood -> filtrate): ** ACTIVE process **
