Adrenal Gland 2 Flashcards
Divisions of the adrenal gland - recall
CGFRM
capsule - zona glomerulosa ( ? ) - zona fasciculata ( ? ) - zona reticularis ( ? ) - adrenal medulla ( ? )
mineralocorticoids: main one is ? (sodium water balance)
glucocorticoids: main ones are ?
sex steroids: ?
catecholamines: ?
C G-FRM think of it as G-FIRM - firm
capsule - zona glomerulosa ( mineralocorticoids ) - zona fasciculata ( glucocorticoids ) - zona reticularis ( androgens ) - adrenal medulla ( catecholamines )
mineralocorticoids: main one is ALDOSTERONE (sodium water balance)
glucocorticoids: main ones are CORTISOL & CORTICOSTERONE
sex steroids: ANDROGENS
catecholamines: NOREPINEPHRINE
(=adrenaline)
Epinephrine
ZONA FASCICULATA - GLUCOCORTICOIDS (cortisol)
Regulation HPA axis:
Hypothalamic (CRH)
Pituitary (ACTH)
Adrenal (cortisol)
the hypothalamus secretes corticotropin-releasing hormone (CRH) which stimulates the corticotropin in the anterior pituitary to release ACTH (adrenocorticotropic hormone) which further acts on the adrenal cortex to secrete cortisol
cortisol then sends negative feedback to the hypothalamus to not secrete CRH - corticotropin (NOT cortisol) releasing hormone
In response to:
low blood glucose (glucocorticoid!)
stressors (stress hormone)
CORTISOL increases the expression of genes that will regulate:
- ?
- immune system
- ? system
- ?
- reproduction
- circadian or ? rhythm -> higher blood concentrations of cortisol in the morning than afternoon/evening.
ZONA FASCICULATA - GLUCOCORTICOIDS (cortisol)
Regulation HPA axis:
Hypothalamic (CRH)
Pituitary (ACTH)
Adrenal (cortisol)
the hypothalamus secretes corticotropin-releasing hormone (CRH) which stimulates the corticotropes in the anterior pituitary to release ACTH (adrenocorticotropic hormone) which further acts on the adrenal cortex to secrete cortisol
cortisol then sends negative feedback to the hypothalamus to not secrete CRH - corticotropin (NOT cortisol) releasing hormone
In response to:
low blood glucose (glucocorticoid!)
stressors (stress hormone)
CORTISOL increases the expression of genes that will regulate:
- metabolism
- immune system
- cardiovascular system
- growth
- reproduction
- circadian or diurnal rhythm -> higher blood concentrations of cortisol in the morning than afternoon/evening.
CRH - a corticotropin-releasing hormone released from the hypothalamus stimulates the corticotropes in the anterior pituitary to release adrenocorticotropic hormone which stimulates the adrenal cortex to release cortisol
glucocorticoids - fascicular zone is linked to secretion of cortisol (mineralocorticoids - glomerulosa secretes aldosterone)
so the cortisol that’s released from the fascicular zone is transported with the help of ? in the blood. thickness of arrow shows that transcortin effects ACTH more than CRH (thickness of level)
so the cortisol that’s released from the fascicular zone is transported with the help of “transcortin” in the blood. thickness of arrow shows that transcortin effects ACTH more than CRH (thickness of level)
Glucocorticoids (cortisol)
“stress”
Biological response to ** ? or ? stimuli **; or a body’s reaction to change to ** maintain ? **
* ?
* Inflammation
* ?
* Physicaltrauma, hypotension (low BP)
* ?
RECALL:
triacylglycerol: main storage of fats
glycerol going to the liver
substrates to make glucose: pyruvates, glycerol, AAs
so cortisol affects
1. liver: gluconeogenesis
2. muscle: protein catabolism
3. adipose tissue: lipolysis
4. immune system: function suppressed
Glucocorticoids (cortisol)
“stress”
Biological response to ** ? or internal stimuli **; or a body’s reaction to change to ** maintain homeostasis **
* hypoglycemia
* Inflammation
* pathogens
* Physicaltrauma, hypotension (low BP)
* emotional
Stress
Diurnal rhythm: Influencing the HPA axis
Circadian rhythm & Stressors (physical, and emotional, including fever, hypoglycemia, and hypotension) affect neurotransmitters which in turn affect the hypothalamus which then stimulates the corticotropin-releasing hormone which affects corticotropes in AP to secrete ACTH which then goes to the target organ i.e. adrenal cortex to secrete circulating cortisol
this cortisol can either send negative feedback to AP or the hypothalamus
Steroid hormones (lipophilic) bound to plasma proteins for transport in the blood
?-? globulin (CBG) transcortin ** ? **
?
Free cortisol binds to ? in cytosol
* H-R complex migrates to the ?
* Stimulates or inhibits expression of
specific ?
(so MUST BE FREE TO BIND TO CORTISOL)
CORTISOL TRANSPORT
?% bound to transcortin
?% bound to albumin
?% UNbound (free state)
Steroid hormones (lipophilic) bound to plasma proteins for transport in the blood
corticosteroid-binding globulin (CBG) ** transcortin **
Albumin
Free cortisol binds to receptors in the cytosol
* H-R complex migrates to the nucleus
* Stimulates or inhibits expression of
specific genes
(so MUST BE FREE TO BIND TO CORTISOL)
** CORTISOL TRANSPORT **
75% bound to transcortin
15% bound to albumin
10% UNbound (FREE state)
CORTISOL EFFECTS - PROTEIN METABOLISM
** Stimulate ? of proteins ***
Mobilization of ? ? from the extrahepatic tissues
Mainly from ? ? (to a lesser extent from the bones)
Serves as substrate for enzyme ?
Serves as substrate for ?
** Reduces cellular ? synthesis **
Decreases ? formation and protein synthesis
If long-term increased release of cortisol:
* Decrease muscle ? synthesis → can
cause muscle ?
* Decreased ? formation can → cause osteoporosis
CORTISOL EFFECTS - PROTEIN METABOLISM
** Stimulate catabolism of proteins ***
Mobilization of AAs from the extrahepatic tissues
Mainly from skeletal muscles (to a lesser extent from the bones)
Serves as substrate for enzyme manufacturing
Serves as substrate for gluconeogenesis
(so the protein are being broken down into AAs and so these AAs serve as substrate for gluconeogenesis and enzymes (needed to fasten this pathway))
** Reduces cellular protein synthesis **
Decreases RNA formation, protein synthesis
If long-term increased release of cortisol:
* Decrease muscle fiber synthesis → can
cause muscle wastage
* Decreased bone formation can → cause osteoporosis
CORTISOL EFFECTS - LIPID METABOLISM
** Increase mobilization of fatty acids from ? tissue (TAG → FFA + Glycerol)
Shift the metabolism from glucose to ? utilization
Enhance the ? of FFAs in cells
Reduced ? transport into fat cells
Can cause obesity **
Depletion of ? fat (SUCH AS IN LIMBS) while increasing ? (abdominal) fat – “potbelly”
→ redirects FFA from adipose tissue to liver and ?
CORTISOL EFFECTS - LIPID METABOLISM
** Increase mobilization of fatty acids from adipose tissue (TAG → FFA + Glycerol)
Shift the metabolism from glucose to fat utilization
Enhance the oxidation of FFAs in cells
Reduced glucose transport into fat cells
Can cause obesity **
Depletion of peripheral fat (SUCH AS IN LIMBS) while increasing visceral (abdominal) fat – “potbelly”
→ redirects FFA from adipose tissue to liver and abdomen
CORTISOL - CARB METABOLISM
** increased Blood Sugar → increased ? (GNG) and glycogenolysis (glycogen found in liver and muscle) **
Stimulates ** synthesis of ? ** involved in GNG
Mobilizes substrates from the ? tissues for GNG
AA → mainly from muscle (and bones to a lesser extent)
Fat (glycerol) → from adipose tissue
** increases Substrate for ? **
Antagonizes ? inhibitory (hormone of abundance) effect of GNG and glycogenolysis in the ?
CORTISOL - CARB METABOLISM
** increased Blood Sugar → increased gluconeogenesis (GNG) and glycogenolysis (glycogen found in liver and muscle) **
Stimulates ** synthesis of enzymes ** involved in GNG
Mobilizes substrates from the extrahepatic (liver) tissues for GNG
AA → mainly from muscle (and bones to a lesser extent)
Fat (glycerol) → from adipose tissue
** increases Substrate for GNG **
Antagonizes insulin’s inhibitory (hormone of abundance) effect of GNG and glycogenolysis in the liver
CORTISOL - CARB METBAOLISM
Potentiates the action of glucagon and epinephrine on glucose metabolism
Recall: glucagon (hormone of “starvation”) and ? → ↑ glycogenolysis
(catabolism of glycogen) - notes: to produce more glucose)
? effect (the presence of one hormone enables another hormone to act)
notes: so it helps other hormones to act as how they should act
** Can cause ? ? (steroid diabetes) **
Increased gluconeogenesis + reduction in
glucose ?*
About ?% of dogs with HAC develop DM (hyperfunction of the adrenal cortex; diabetes Mellitus)
Chronic administration of glucocorticosteroids can cause ? diabetes
CORTISOL - CARB METBAOLISM
Potentiates the action of glucagon and epinephrine on glucose metabolism
Recall: glucagon (hormone of “starvation”) and epinephrine → ↑ glycogenolysis
(catabolism of glycogen) - notes: to produce more glucose)
permissive effect (the presence of one hormone enables another hormone to act)
notes: so it helps other hormones to act as how they should act
** Can cause DIABETES MELLITUS (steroid diabetes) **
Increased gluconeogenesis + reduction in
glucose utilization*
About 20% of dogs with HAC develop DM (hyperfunction of the adrenal cortex; diabetes Mellitus)
Chronic administration of glucocorticosteroids can cause steroid diabetes
so the cortisol has following effects:
SKELETAL MUSCLE
- lowers glucose uptake, glycogen, protein synthesis
- increases protein breakdown
whereas insulin does the opposite for instance it increases glucose uptake (trying to decrease glucose levels roaming freely and so uptake by skeletal muscle)
LIVER
- increases gluconeogenesis
ADIPOSE TISSUE
- increases lipolysis
- increases release of NEFAas and TGs
- NEFAas main substrates are:
1. AA from protein catabolism
2. NEFAs from adipose tissue
CORTISOL - IMMUNE SYSTEM
- ? lysosomal membranes
Decreasing release of ? enzymes by damaged cells - ↓ synthesis of ? and ? (both are eicosanoids)
↓ vasodilation, permeability and ? blood cell migration - ↓ secretion of ? by mast cells
- ↓ phagocytosis and suppresses ? formation
- Prevents ? tissue synthesis
ALL THESE POINTS LEAD TO LOWERING OF ? SYSTEM ?
CORTISOL - IMMUNE SYSTEM
- stabilizes lysosomal membranes
Decreasing release of proteolytic enzymes by damaged cells - ↓ synthesis of prostaglandins and leukotrines (both are eicosanoids)
↓ vasodilation, permeability and white blood cell migration - ↓ secretion of histamine by mast cells
- ↓ phagocytosis and suppresses antibody formation
- Prevents connective tissue synthesis
ALL THESE POINTS LEAD TO LOWERING OF IMMUNE SYSTEM INFLAMMATION
Cortisol - other effects
** excessive cortisol inhibits secondary functions not necessary for ? **
? system
Various mechanism of actions → Reduces reproductive ?
?
Various mechanism of action → i.e., inhibiting insulin-like growth factor 1 (IGF-1)
- ? system: *
Increases the sensitivity of vascular smooth muscle to ? (i.e., catecholamines)
Suppresses the release of ? (i.e., nitrous oxide)
Helps maintain blood ?
Cortisol - other effects
** excessive cortisol inhibits secondary functions not necessary for SURVIVAL **
reproductive system
Various mechanism of actions → Reduces reproductive ?
growth
Various mechanism of action → i.e., inhibiting insulin-like growth factor 1 (IGF-1)
- cardiovascular system: *
Increases the sensitivity of vascular smooth muscle to vasoconstrictors (i.e., catecholamines)
Suppresses the release of vasodilators (i.e., nitrous oxide)
Helps maintain blood pressure
zone reticularis - androgens
Androgens are hormones that interact with male sex hormone receptors
Dehydroepiandrosterone (?)
? -> ? -> released into the blood stream → ? or ? to produce testosterone and estrogens **
- Less active than testosterone
- ? androgens action is not significant in most animals (mostly contribute to increase libido and secondary sexual characteristics in humans)
zone reticularis - androgens
Androgens are hormones that interact with male sex hormone receptors
Dehydroepiandrosterone (DHEA)
DHEA -> androstenedione -> released into the blood stream → testis or ovaries to produce testosterone and estrogens **
- Less active than testosterone
- adrenal androgens action is not significant in most animals (mostly contribute to increase libido and secondary sexual characteristics in humans)
(androgen’s production is regulated by ACTH)
ADRENAL MEDULLA
Chromaffin cells → ? cells* *modified post-ganglionic sympathetic motor neurons, lack ? and ?
Short-term (acute) stress Fight or flight response
** ? from ?-ganglionic ? neurons → binds to nicotinic receptors on the chromaffin cells → secretion of ? **
Catecholamines:
EPI (epinephrine) ?%
NE (norepinephrine) ?%
IMP info: preganglionic sympathetic neuron from the spinal cord and then it synapses into adrenal medulla
pre-ganglionic sympathetic neurons smtms secrete acetylcholine such as in this case;
ADRENAL MEDULLA
Chromaffin cells → neuroendocrine cells* *modified post-ganglionic sympathetic motor neurons, lack dendrites and axons
Short-term (acute) stress Fight or flight response
** acetylcholine from pre-ganglionic sympathetic neurons → binds to nicotinic receptors on the chromaffin cells → secretion of catecholamines **
Catecholamines:
EPI (epinephrine) 80%
NE (norepinephrine) 20%
IMP info: preganglionic sympathetic neuron from the spinal cord and then it synapses into adrenal medulla
pre-ganglionic sympathetic neurons smtms secrete acetylcholine such as in this case;
