Adrenal Gland Flashcards
Glucocorticoids, mineral corticoids, and catecholamines are released from what gland?
Adrenal gland
Blow flood from suprarenal arteries creates a sinusoid system in the adrenal medullae, this help modulate what?
Enzyme activity
What are the 3 layers of the adrenal cortex?
- Z. glomerulosa (outer most)
- Z. fasciculata
- Z. reticularis (inner most)
“Go Find Rex, Make Good Sex”
T or F: All steroids share the same first step (cholesterol converted to prenenolone via desmolase)?
True
Mobilization of cholesterol (via ATII receptor, K+ channels) → free cholesterol travels to mitochondria → inner mitochondrial membrane (via STaR) → converted to pregnenolone via desmolase (this is the rate limiting step and dependent on STaR)
What are the rate limiting enzymes in the conversion of cholesterol to pregnenolone?
Desmolase, dependent on STaR
The Z. glomerulosa produces what hormones?
mineralcorticoid: Aldosterone
T or F: Aldosterone provide negative feedback on CRH & ACTH
FALSE
Cortisol is the only corticoid that provides negative feedback on CRH & ACTH
The Z. glomerulosa lack what enzyme forcing pregnenolone to only be converted to progesterone => aldosterone?
Lacks 17𝛂-hydroxylase
MR type 1 receptors are greatest in what organ?
Kidney
What hormones stimulates ACTH to produce aldosterone?
ATII (RAAS)
What layer of the adrenal cortex lacks 17,20-lyase (prevents production of androstenedione) and lacks aldosterone synthase (prevents production of aldosterone)?
Z. fasciculata
T or F: GR Type II receptors are located in all cells?
True
The cortisol-cortisone shunt includes what two enzymes?
11B-HSD1 (activates: cortisone to cortisol)
11B-HSD2 (inactivates: cortisol to cortisone)
Liver cortisol → kidney where inactivated by 11B-HSD2, cortisone can’t bind to MR → cortisone travels back to liver → activated by 11B-HSD1 → binds to GR receptors
What hormones lead to the production of cortisol?
GnRH → CRH → ACTH → Cortisol (glucocorticoid)
T or F: Cortisol provide negative feedback to GnRH, CRH, and ACTH
TRUE
What corticoids produce a long term response to stress?
Mineralocorticoids (aldosterone) and glucocorticoids (cortisol)
What enzyme does Z. reticularis lack preventing production of aldosterone and cortisol?
21𝛽 Hydroxylase
What hormone class does Z. reticularis produce?
Androgens (androtenedione)
Do angrogens have feed back on CRH and ACTH?
No
Cortisol is the only hormone that has negative feedback on CRH and ACTH
The following are a result of a deficiency of what enzyme?
- No conversion of: progesterone → 11-deoxycorticosterone OR 17-hydroxyprogesterone → 11 deoxycortisol
- Cortex does NOT produce glucocorticoids or mineralocorticoids → sodium loss and hypoglycemia
- Steroid intermediates build up → converted to androgens → Adrenogenital syndrome & ↑ 17-ketosteroids in urine
- ↑ ACTH (b/c lack of neg feedback from cortisol) → tropic effects
21𝛽 Hydroxylase Deficiency
Plasma levels of Cortisol and what other hormone are reflect pulsatile and circadian release of ACTH?
Cortisol and Androtenidione (Androgens)
Androstenedione are a major source of androgens for females, these produce what effect in the female? (2)
secondary sex charactristics and libido
Does catecholamine synthesis take place in the adrenal cortex or medulla?
Medulla (specifically chromaffin cells)
What is the rate limiting step in catecholamine synthesis?
Tyrosine conversion to DOPA via tyrosine hydroxylase
Tyrosine conversion to dopamine takes place in the cytosol or granules?
Cytosol
Dopamine conversion to NE takes place in the cytosol or granules?
Granules
NE conversion to E takes place in the cytosol or granules?
Cytosol
What enzyme is responsible for conversion of NE to E?
phenylethanolamine-N-methyltransferase
Where is Epi store in the body?
Granules
Activation of tyronsine hydroxylase is a result of acute or chromic stimulation of catecholamine synthesis?
Acute
Increased expression and concetration of tyronsine hydroxylase is a result of acute or chromic stimulation of catecholamine synthesis?
Chronic
T or F: Catecholamine secretion result in a rapid and short lived response (t1/2 = ~ 2min) ?
True.
Response to “fight or flight”, hypotension, shock, HF, hypoglycemia
Increased HR, ↑ glycogenolysis, gluconeogenesis, glucagon secretion and lipolysis are the effects of what hormone?
Epinephrine
What enzyme monitors NE > Epi degradation and secretion?
MOA (neural cytoplasm)
What enzyme monitors Epi > NE degradation and secretion?
Catechol-0-methyltransferase (COMT) (heart, liver, kidney)
T or F: Plasma levels of cortisol are greater than plasma levels of aldosterone?
TRUE
Mineralocorticoid receptors (MR) and glucocorticoid receptors (GR) are structurally similar. Does aldosterone or cortisol bind with higher affinity?
Cortisol
Under healthy conditions will cortisol bind to MR receptors?
No
What 3 mechanisms prevent cortisol from binding to MR receptors under health conditions?
- Cortisol bound to albumin & cortisol-binding globulin (only small % of free hormone crosses cell membrane)
- Aldosterone converts cortisol to cortisone (↓ cortisol affinity to MR)
- Aldosterone dissociates from MR more slowly than cortisol
Over expression of 11B-HSD1 in adipose tissues will lead to over time?
Production of excess cortisol → insulin resistance/ features of metabolic syndrome
During what time of the day are cortisol/ATCH levels highest?
Morning
Levels rise during sleep/ peak in AM & drop throughout the day (reflects circadian release of ACTH)
Does stress increased the burst amplitude of CRH or the duration of CRH release?
Burst amplitude→ ↑ ACTH → ↑ Cortisol
What is the primary action of cortisol
↑ blood glucose
What hormone do the following describe?
↑ glycogenolysis (early stages of fasting)
↑ glycogenesis (late-stage fasting)
↑ gluconeogenesis
↑ glucose sparing
↓ glucose uptake in tissues other than brain
Cortisol
Epinephrine will increase or decrease insulin secretion via 𝛂-adrenergic stimulation of 𝛃-cells
Decrease insulin secretion
Generally, does epinephrine favor release or storage of energy stores
Release (during short term stress)
Generally, does Cortisol favor release or storage of energy stores?
Release (during long term stress)
↑ protein catabolism, ↑ lipolysis lead to enhanced what?
Gluconeogenesis
What hormone maintains BP by maintain a-1 responsiveness to catecholamines?
Cortisol
What hormone inhibits bone formation, decreases bone density, and leads to muscles wasting/weakness?
Cortisol
What hormone thins skin, impair collagen formation an decreases connective tissue support in capillaries?
Cortisol
What corticoid is stimulated by ↓ BP/ ECF volume
Aldosterone
ATII > ↑ plasma K+ > ACTH will increase the secretion of what hormone?
Aldosterone
Aldosterone binds to MR or GR stimulating Na reabsorption & K secretion?
MR
What is the net effect of Aldosterone on ECF?
Expansion of ECF volume
Conn’s syndrome is due to increased or decreased levels of aldosterone?
Increased
- Aldosterone secreting tumor
- hypernatremia, fluid retention, hypokalemia, metabolic alkalosis, HTN = ↓ renin
Will a 17a-hydroxylase deficiency result in increased or decreased levels of aldosterone?
Decreased
- ↑ corticosterones, but HTN = ↓ renin SO No ATII → ↓ aldosterone
- hypokalemia, metabolic alkalosis
Cushing’s syndrome is due to high or low levels of cortisol?
HIGH
↑ active cortisol binds to aldosterone receptors (MR) → aldosterone-like effects
What enzyme is down regulated in Cushing’s syndrome?
11B-HSD2 → ↑ active cortisol binds to aldosterone receptors (MR) → aldosterone-like effects
Primary adrenocortical insufficiency leads to what disease?
Addison’s Disease: autoimmune destruction of the adrenal cortex → ↓ synthesis of all adrenocortical hormones
Low levels of what hormone will produce hypoglycemia during stress, weight loss, muscle weakness
Cortisol
Low levels of what hormone will produce hyperkalemia, hypotension, metabolic acidosis, salt craving
Aldosterone
Low levels of what hormone will produce ↓ 2˚ sex characteristic in postpuberty females, ↓ libido
Androgrens
Will ACTH secretion by increased or decreased in Addison’s disease?
Increased due to lack of negative feedback from cortisol
High levels of what hormone will produce hyperpigmentation of elbows, knees, nipples, scars (𝛂-MSH fragment)
ACTH
With secondary (failure of corticotrophs to adequately secrete ACTH) and Tertiary (insufficient CRH) adrenocortical insufficiency levels of what two hormones will be low? What hormone will have normal levels?
- Cortisol and androgen deficiency
- Normal aldosterone
Will you have hyperpigmentation w/ secondary and Tertiary adrenocortical insufficiency?
No
Moon face, buffalo hump, central obesity, thin skin/striate and muscle wasting are sx of what mineralcorticoid disease?
Cushing’s
Excess glucocorticoids and androgens
Primary adrenal hyperplasia decreased ACTH levels, this leads to what syndrome?
Cushing’s syndrome
An overactive pituitary increased ACTH levels this leads to what disease?
Cushing’s
What are the effects of F being expose to ↑ DHEA and androstenedione in utero (adrenogenital syndrome)?
Masculinization of female (female pseudohermaphrodite): penis like clitoris, scrotum like vagina, ovaries present, primary amenorrhea
What are the effects of F having ↑ DHEA and androstenedione as an adult (Adrenogenital syndrome)?
Adult females develop male traits = deepening of voice, ↑ muscle mass, amenorrhea and hirsutism, clitoral enlargement and acne
A pheochromocytoma (catecholamine secreting tumor) will lead to hyper or hypo function of the adrenal medulla?
Hyperfunction –> HTN, ↑ HR, chest pain, excessive sweating, HA, hyperglycemia, fatigue
(Adrenomedullary Dysfunction)
Following an adrenalectomy, a pt will have hyper or hypo function of the adrenal medulla
HYPO –> no overt clinical difficulties
Adrenomedullary Dysfunction
Cushing’s syndrome (hypercortisolism) is associated with mutated secretion of what hormone?
growth hormone
