9) Adrenal Gland Flashcards
What stimulates the release of CRH?
- Decrease in plasma cortisol
- Hypoglycemia
- Stress
What inhibits the release of CRH?
Increase in plasma glucocorticoids
Where are the adrenal glands located?
Above or medial to the upper poles of the kidneys
What is the thickest layer of the adrenal cortex?
Zona fasciculata
What are the three zones of the adrenal cortex?
- Zona glomerulosa
- Zona fasciculata
- Zona reticularis
What is the importance of the structure of the adrenal gland in terms of the proximity between the adrenal cortex and medulla?
- Glucocorticoids produced by the adrenal cortex (cortisone, cortisol) are required for the synthesis of catecholamines
- Catecholamines are synthesized by the adrenal medulla
- Glucocorticoids travel from the cortex to the medulla directly
Which hormone does the zona glomerulosa produce?
Aldosterone
Which hormone does the zona fasciculata produce?
Cortisol
Which hormone does the zona reticularis produce?
Sex steroids
Which hormones does the adrenal medulla produce?
Catecholamines (epinephrine and norepinephrine)
The zona ________ cannot synthesize cortisol or androgens.
glomerulosa
Why can’t the zona glomerulosa synthesize androgens or cortisol?
Because it lacks 17a-hydroxylase
Why can’t the zona fasciculata form sex steroids?
Because it lacks 17-lyase
What is the first step common to all steroids? Where does it take place?
- Formation of pregnenolone from cholesterol
- Mitochondria
What determines which steroid is produced in a cell or tissue?
Tissue-specific expression of enzymes
Where are enzymes for steroid hormone synthesis located within the cell?
- Mitochondria and endoplasmic reticulum
- Steroid intermediates have to shuttle back and forth
How do most steroids differ?
- By minor modifications of side groups
- Often hydroxyl groups
What is the StAR protein?
- Rate-limiting enzyme for the transport of cholesterol
- Carries the cholesterol across the mitochondrial membrane to the inner surface
What is the function of P450scc?
Side chain cleavage of cholesterol to pregnenolone
The uptake of cholesterol is regulated by what?
- StAR protein
- Steroid Acute Regulatory protein
StAR is ____-inducible.
cAMP
What hormones increase StAR?
- Trophic hormones
- ACTH in the adrenal gland
- Gonadotrophins in the gonads
Where is cortisol stored intracellulary?
There is NO cellular storage of cortisol
What is cortisol converted to in the liver? For what purpose?
- Inactive cortisone and other metabolites
- For excretion in urine
What are the two main effects of cortisol? (2)
1) Carbohydrate and protein metabolism
2) Anti-inflammatory effects
What enzyme converts cortisol to inactive cortisone?
Hydroxysteroid dehydrogenase type II
What enzyme converts inactive cortisone to cortisol?
Hydroxysteroid dehydrogenase type I
Which hormone can activate the aldosterone receptor?
Cortisol
How does the plasma concentration of cortisol compare to aldosterone?
Cortisol is 100 to 1000-fold higher than aldosterone
What must aldosterone-specific cells do to assure that they respond specifically to aldosterone?
Inactivate cortisol
A deficiency in the enzyme responsible for converting cortisol to cortisone results in what syndrome?
- AME syndrome
- Apparent mineralocorticoid excess
Skin, liver, adipose, CNS, and placenta possess hydroxysteroid dehydrogenase type __.
1
Kidney, colon, sweat glands, salivary glands, and placenta possess hydroxysteroid dehydrogenase type __.
2
What occurs to hydroxysteroid dehydrogenase type 2 when cortisol levels are too high?
- HSD2 is overwhelmed
- Cortisol stimulates Na+/K+ exchange in the kidney
- Causes hypokalemia and hypertension
A component of which food is an inhibitor of hydroxysteroid dehydrogenase type 2?
Licorice
What type of receptor is the cortisol receptor?
Class I (cytosolic) intracellular receptor
The effects of cortisol are (similar/opposite) to insulin and (similar/opposite) to GH.
opposite
similar
What are the effects of cortisol on muscle cells, adipocytes, and lymphocytes?
Increase in catabolism
What are the effects of cortisol on the liver?
- Increase in glycogen synthesis
- Increase in gluconeogenesis
What is the overall effect of cortisol on blood glucose and glycogen store?
- Increase in blood glucose
- Despite the increase in glycogen storage
Cortisol is (pro/anti)-inflammatory.
anti-inflammatory
How does cortisol affect lymph nodes, the thymus, lymphocytes, and antibodies? How does that affect the patient’s health overall?
- Atrophy of the lymph nodes and thymus (activation of apoptosis)
- Decrease in lymphocytes and antibodies
- Patients become susceptible to infections
How is cortisol linked to hypertension through norepinephrine?
Cortisol sensitizes arterioles to the action of norepinephrine
How is cortisol linked to carbohydrate metabolism through norepinephrine?
- Permissive effect on the action of norepinephrine on carbohydrate metabolism
- Glycogenolysis leads to hyperglycemia
How does cortisol affect the CNS?
Increased activity of the CNS, leading to euphoria
Cortisol may act as a ___________ because it interacts with its receptor.
mineralocorticoid
How does cortisol affect blood glucose, amino acids, and fatty acids? Why?
- Increase in blood glucose, amino acids, and fatty acids by catabolism
- They are now available to help resist stress
ACTH activates cortisol production via which signalling pathway?
G-protein/cAMP
After a long suppression of synthesis of ACTH, what may be needed to allow for ACTH synthesis to resume?
- Time is required
- Hypothalamic axis does not respond well, and requires time to produce the cyclical release of ACTH
Describe the rhythm of cortisol-releasing hormone release.
Highest level early in the morning (diurnal rhythm)
What is the transport protein for cortisol?
Corticosteroid Binding Globulin (CBG or Transcortin)
Where is CBG synthesized?
- Synthesized in the liver
- Highest affinity for cortisol
What percentage of cortisol is bound to CBG? What percentage is “free” in plasma? What occurs to the rest?
- 75% bound to CBG
- 10% is free
- 15% bound to serum albumin
Bound cortisol is protected from what? What is the effect?
- Protected from inactivation by the liver
- Maintains a pool of circulating cortisol by delaying metabolic clearance
How does the liver inactivate free steroids?
By increasing water solubility
How does Cushing’s disease affect blood glucose?
- Increased levels of blood glucose
- Diabetes mellitus
How does Cushing’s disease affect body fat?
- Increased body fat and redistribution
- Central obesity and moonface
How does Cushing’s disease affect the immune system?
Increased susceptibility to infection
Which types of tumours may cause Cushing’s disease?
- CRH-producing tumour
- ACTH-producing tumour
- Cortisol-producing adrenal tumour
What are the four causes of spontaneous Cushing’s disease?
1) CRH-producing tumour
2) ACTH-producing tumour
3) Cortisol-producing adrenal tumour
4) Lack of feedback control by cortisol
What is the most common cause of Cushing’s disease?
- Iatrogenic (“brought forth by the healer”)
- Results from chronic glucocorticoid therapy
What is the treatment for Cushing’s disease?
- Removing the cause of hypersecretion without permanently damaging the adrenal or pituitary
- Microsurgery
- Radiation therapy
- Pharmacologic inhibition of ACTH secretion
What is Addison’s disease?
Adrenal hypofunction
What is the most common cause of Addison’s disease?
The destruction of the adrenal gland by an autoimmune response
What are symptoms of Addison’s disease?
- Fatigue
- Weakness
- Faintness
- Nausea
- Vomiting
- Low-blood pressure
- Salt craving
- Pain in muscles and joint
- Excessive freckling
What causes the excessive freckling in Addison’s disease?
- The pituitary gland is attempting to stimulate the production of cortisol
- Release of MSH from the production of ACTH from POMC
How does Addison’s disease affect kidney function? Why?
- Aldosterone is low or absent
- Water and sodium loss from the kidney
- Low fluid volume and low blood pressure
- Salt appetite
How does Addison’s disease affect the liver?
- Liver function decreases due to absent cortisol
- Extremely low sugar
How does Addison’s disease affect the stomach?
- Stomach digestive enzymes decrease due to absent cortisol
- Vomiting, diarrhea, cramps
- Low fluid volume
What is the treatment for Addison’s disease?
Life-long glucocorticoid and mineralocorticoid therapy
What is the main function of aldosterone in terms of sodium and potassium?
- Recovery of sodium in the renal filtrate
- Enhanced potassium secretion into the urine to balance the charge difference
What are the three physical attributes of plasma that maintain homeostasis of the blood system?
- Volume
- Blood pressure
- Osmolarity
What is the major determinant of blood pressure in arteries?
The diameter of arterioles
Aldosterone increases sodium reabsorption in which areas?
- Distal tubules of the kidney
- GI tract
- Salivary gland
- Sweat gland
The release of aldosterone is mainly under the control of what?
Angiotensin II
What secretes angiotensinogen?
Liver
What catalyzes the conversion of angiotensinogen to angiotensin I?
Renin
What catalyzes the conversion of angiotensin I to angiotensin II? What is it secreted by?
- Angiotensin converting enzyme
- Surface of pulmonary and renal endothelium
How does angiotensin II affect blood pressure and arteriole diameter?
- Arteriole vasoconstriction
- Increase in blood pressure
How does angiotensin II affect the pituitary gland?
- ADH secretion
- H2O reabsorption at the collecting duct
What is the overall effect of angiotensin II?
- Water and salt retention
- Effective circulating volume increases
What is the source of renin?
Juxtaglomerula apparatus
What is the function of macula densa cells in the distal tubule?
Detect sodium levels in the kidney tubule
What is the function of juxtaglomerula cells?
Detect blood pressure and release renin in response to low blood pressure
What causes the rapid pressor response of angiotensin II?
Change in peripheral resistance through direct vasoconstriction
What causes the slow pressor response of angiotensin II?
Change in renal function (increased sodium reabsorption both direct and aldosterone-mediated)
How does the release of angiotensin II affect the sympathetic nervous system and the adrenal medulla?
- Increase in sympathetic discharge
- Increase in adrenal medullary catecholamine release
Aldosterone increases the recovery of ______.
sodium
How does aldosterone increase the recovery of sodium?
- Promotes the insertion of additional sodium channels into the luminal membrane
- Adds additional Na+/K+ ATPase channels into the basolateral membrane of the tubule
What are the main sites of action of aldosterone?
- Distal tubules and collecting ducts of the kidneys
- Other secretory systems (sweat glands, salivary glands, colon)
Aldosterone promotes the retention of ______ and the excretion of ______ and ___ into the lumen of the tubules.
sodium
potassium
H+
Aldosterone sensitizes arterioles to (vasodilators/vasoconstrictors).
vasoconstrictors
Does aldosterone act instantaneously?
No, it has a lag period of one hour
Why does aldosterone have a lag period of one hour?
Aldosterone-induced enzymes have to be synthesized de novo
What kind of receptors are aldosterone receptors?
Intracellular receptors that may activate the expression of a series of genes
What are aldosterone-responsive target tissues that are capable of inactivating cortisol to cortisone?
- Kidney
- Colon
- Salivary glands
AME may be induced by _______.
licorice
What is the most important regulatory system of aldosterone secretion?
Renin-angiotensin system
The release of renin by juxtaglomerular cells is activated by what?
- Decrease in plasma fluid volume
- Decrease in plasma osmolarity
How does angiotensin II affect glomerular filtration rate?
Reduces glomerular filtration rate
What are the three major factors that regulate renin release? (3)
1) Baroreceptors in the wall of the afferent arteriole (decrease in pressure)
2) Neural input via the sympathetic nervous system
3) NaCl concentration in the lumen of the distal tubules (low NaCl)
How does NaCl concentration affect renin release?
Low NaCl = low blood pressure = increase in renin
What feedback control system regulates renin release?
Angiotensin II
How do low potassium levels affect aldosterone?
Reduces aldosterone
How do low potassium levels affect renin?
Stimulates renin
What is Conn’s syndrome?
Hypersecretion of aldosterone
What are the two major causes of Conn’s syndrome?
- Adrenal hyperplasia (60%)
- Tumour (40%)
Conn’s syndrome results in excess excretion of which ions?
Potassium and H+
What are the effects of excess excretion of K+ and H+ in Conn’s syndrome?
- Serum alkalosis
- Neuropathy (hypocalcemia)
How does Conn’s syndrome affect water homeostasis, sodium reabsorption and blood pressure?
- Increased water retention
- Increased sodium reabsorption
- Increased blood pressure
What is the function of atrial natriuretic peptide (ANP)?
- Increases the excretion of H2O and sodium
- Reduces blood volume
What produces ANP? How is it stored?
- Produced by cardiocytes
- Stored in granules
Where are ANP receptors located?
- Glomeruli
- Medullary collecting ducts of the kidney
- Zona glomerulosa of the adrenal cortex
- Peripheral arterioles
An (increase/decrease) of sodium and water intake stimulates the release of ANP from cardiocytes.
increase
How does ANP affect plasma renin and aldosterone?
Reduction in plasma renin and aldosterone
How does ANP affect renal blood flow, water and sodium excretion?
- Increase in renal blood flow
- Increase in water excretion
- Increase in sodium excretion
Why does ANP increase sodium excretion?
- Increase in filtration rate
- Inhibition of reabsorption of sodium
How does ANP affect vasoconstriction by angiotensin II?
Inhibits vasoconstriction by angiotensin II
Which sex steroids are synthesized in females? Which are synthesized in males?
- Females: estrogens and progesterones
- Males: androgens
The adrenal cortex contributes to the production of which metabolites, implicated in the production of sex steroids? What is it regulated by?
- DHEAS
- Androstenedione
- Regulated by ACTH and CRH
What is the primary role of sex steroids in the adrenal cortex? When does the release increase in the life cycle?
- Unclear
- Body hair growth in females (adrenarche)
- Increase before puberty
- Responsible for growth spurt in middle childhood
What is andrenarche?
- Increased expression of adrenal androgens (without increased cortisol levels)
- During puberty
What is congenital adrenal hyperplasia (CAH)?
- Masculinization of external genitalia at birth
- Excessive androgen production (hyperplasia of the adrenal glands)
What does the genitalia of females ressemble in individuals with CAH?
- Labia comes together to look like a scrotum
- Clitoris enlarges to look like a penis
How does the primordial gonad become an ovary in a normal female?
- Lack of Y chromosome
- Lack of SRY gene (on Y chromosome)
Is the Mullerian duct maintained in males or females? What does it lead to?
- Females
- Uterus oviduct
Why don’t males possess the Mullerian duct?
Because they possess Anti-Mullerian hormone (AMH)
Is the Wolffian duct maintained in males or females?
Males
What causes the presence of female external genitalia in normal females?
- Lack of testosterone
- Lack of DHT
What causes the presence of masculinized external genitalia in CAH females?
- Presence of testosterone (by the adrenal gland)
- Presence of DHT
What are the effects of testosterone on the brain in CAH females?
Sexual differentiation of the brain
Do females with CAH possess a uterus and ovaries?
Yes, but they also possess masculinized external genitalia
What is the enzyme defect in CAH? What are the effects on the hormones produced by the adrenal gland?
- 21-hydroxylase (autosomal recessive)
- Low cortisol production
- Low aldosterone production (salt appetite increases)
How does low cortisol production in CAH females affect the hypothalamic pituitary axis?
Reduced negative feedback, which increases the secretion of CRH and ACTH
What is the treatment for CAH females?
- Surgical correction at birth
- Raise as girls (possess tendency towards male play patterns)
