CH6 Adrenal Gland Flashcards
What two types of hormones does the adrenal gland secrete? What are they?
steroid hormones (glucocorticoids, mineralocorticoids, androgens), catecholamines (norepinephrine, epinephrine)
What kinds of steroid hormones secreted by the adrenal cortex? Which specific ones are secreted by which layer?
glucocorticoids (cortisol, zona fasciculata & zona reticularis in the cortex), mineralocorticoids (aldosterone, zona glomerulosa in the cortex), androgens (dehydroepiandrosterone DHEA, zona fasciculata & zona reticularis in the cortex)
What are the catecholamines secreted by the adrenal gland? What are they derived from? Which part secretes them?
norepinephrine, epinephrine; derived from L-tyrosine; secreted by medulla
What is the embryologic origin of the adrenal cortex?
mesodermal tissue
What is the embryologic origin of the adrenal medulla?
neural crest cells
What are the 3 zones of the adrenal cortex? what do they produce?
zona glomerulosa (mineralocorticoid aldosterone), zona fasciculata (glucocorticoid cortisol & androgen DeHydroEpiAndrosterone), zona reticularis (glucocorticoid cortisol & androgen DeHydroEpiAndrosterone)
What stimulates sex steroid release from adrenal glands?
hypothalamic-pituitary-adrenal hormone stimulation
What stimulates catecholamine release from adrenal glands?
direct sympathetic stimulation (sympatho-adrenal)
What is the circulation system of the adrenal gland?
superior, middle, & inferior suprarenal aa –> drain into adrenal medulla (allowing for steroid hormones released from cortex to influence catecholamine synthesis) –> renal vein (right drains into IVC, left drains into left renal artery)
What is the distinguishing feature of the outer layer of the adrenal cortex? What does it produce?
Zona Glomerulosa contains abundant smooth ER. produces mineralocorticoid aldosterone.
What is the distinguishing feature of the middle layer of the adrenal cortex? What does it produce?
Zona Fasciculata contains abundant lipid droplets. produces glucocorticoids cortisol and corticosterone, & also produces androgens Dehydroepiandrosterone DHEA and Dehydroepiandrosterone-sulfat DHEAS
What is the distinguishing feature of the inner layer of the adrenal cortex? What does it produce?
Zona Reticularis develops postnatally (approx. 3 yrs old). produces glucocorticoids cortisol and corticosterone, & also produces androgens dehydroepiandrosterone DHEA and dehydroepiandrosterone-sulfate DHEAS
Track Glucocorticoid Synthesis via progesterone.
(Cholesterol Ester Hydrolase) converts cholesterol-esters –> cholesterol. (P45side-chain cleavage enzyme) converts cholesterol –> pregnenolone. Pregnenolone –> Progesterone –> 11-deoxycorticosterone –> CORTICOSTERONE
Track Glucocorticoid Synthesis via 17-alpha-hydroxypregnenolone.
(Cholesterol Ester Hydrolase) converts cholesterol-esters –> cholesterol. (P450side chain cleaving enzyme) converts cholesterol –> 17-alpha-hydroxypregnenolone. 17-alpha-hyxroxypregnenolone –> 17-alpha-hydroxyprogesterone –> 11-deoxycortisol –> CORTISOL
Track Mineralocorticoid Synthesis.
(Cholesterol Ester Hydrolase) converts cholesterol esters –> cholesterol. (P450side chain cleaving enzyme) converts cholesterol –> pregnenolone. Pregnenolone –> progesterone –> 11-deoxycorticosterone –> corticosterone –> ALDOSTERONE
Why does Mineralocorticoid Synthesis only use the Progesterone pathway?
Zona Glomerulosa doesn’t have 17-alpha-hydrolase. (required to convert pregnenolone –> 17-a-OH-pregnenolone)
Track Androgen Synthesis via 17-alpha-hydroxypregnenolone.
(Cholesterol Ester Hydrolase) converts cholesterol esters –> cholesterol. (P450side chain cleaving enzyme) converts cholesterol –> pregnenolone. Pregnenolone –> 17-alpha-hydroxypregnenolone –> Dehydroepiandrosterone DHEA
Track Androgen Synthesis via 17-alpha-hydroxyprogesterone.
(Cholesterol Ester Hydrolase) converts cholesterol esters –> cholesterol. (P450side chain cleaving enzyme) converts cholesterol –> pregnenolone. Pregnenolone –> 17-alpha-hydroxypregnenolone –> 17-alpha-hydroxyprogesterone –> ANDROSTENEDIONE
What stimulates Glucocorticoid Cortisol release? What is an important feature of the stimulation of Glucocorticoid Cortisol release?
ACTH (corticotropin); it is pulsatile & follows a circadian rhythm that is sensitive to environmental & internal factors (light, sleep, stress, disease)
What kind of receptor does ACTH bind to? What kind of cell? What is the biological effect?
Gs protein-coupled plasma membrane melanocortin 2 receptor on Adrenocortical Cells. Activates PKA –> phosphorylates Cholesteryl-ester Hydrolase (increase activity) & activates + increase synthesis of Steroid Acute Regulatory (STAR) Protein. [both of these enzymes catalyze rate-limiting steps in steroidogenesis]
What is STAR protein? What is its significance?
STeroid Acute Regulatory Protein mediates cholesterol transfer to inner mitochondrial membrane for P450scc (side chain cleaving) enzyme [cholesterol–>pregnenolone]; this is one of the rate-limiting steps in steroidogenesis
What feedback mechanism regulates the Hypothalamic-Pituitary-Adrenal (HPA) Axis? What is the HPA axis?
HPA axis: circuit of CRH –> ACTH –> Cortisol; Cortisol inhibits release of CRH and ACTH
What is the binding protein for circulating Cortisol? What stimulates production of this protein?
glucocorticoid-binding alpha2-globulin (transcortin / cortisol-binding protein); stimulated by estrogen
What organs inactivate Cortisol?
liver, kidney
What is the inactive form of Cortisol?
Cortisol –> cortisone –> tetrahydrocortisol/tetrahydrocortosone (known as 17-hyxroxycorticosteroids)
What is 11beta-hydroxysteroid Dehydrogenase?
NADP dependent reductase; 2 types: type I (cortisone –> cortisol), type II (cortisol –>cortisone)
Which form of 11beta-hydroxysteroid dehydrogenase has a higher affinity for its substrate? What does it do?
type II, converts cortisol –> cortisone
What is the purpose of aldosterone?
stimulate K+ excretion & increase Na+ resorption
What stimulates release of aldosterone?
angiotensin II & high K+ concentration
What does angiotensin II do?
vasoconstriction & stimulate aldosterone
What is the renin-angiotensin-aldosterone system a response to?
decrease of blood volume
What do the adrenal androgens (DHEA / DHEAS) get converted into? What happens to that hormone?
DHEA/DHEAS –> androstenedione –> dihydrotestosterone OR 17beta-estradiol
What are the 2 types of steroid hormone receptors?
type I (mineralocorticoid receptor) & type II (corticosteroidreceptor)
What is special about type I steroid hormone receptor?
specific for mineralocorticoids, but have a high affinity for glucocorticoids
How is the specificity for type I steroid hormone receptor enhanced?
1) glucocorticoids are bound to glucocorticoid-binding-alpha2-globulin & albumin. 2) aldosterone target cells have 11beta-hydroxysteroid-dehydrogenase-type-II activity. 3) mineralocorticoid receptor discriminates between aldosterone and glucocorticoids (glucocorticoids dissociate faster than aldosterone from type I receptors)
What is the overall effect of Glucocorticoid Cortisol?
increase blood glucose concentration
How does cortisol effect blood vessels?
maintain vascular integrity/fluid volume & responseiveness ot catcholamine
How does cortisol effect immune function?
anti-inflammatory effect
What is the physiological effect of Aldosterone on the distal tubule Principal Cells?
increase synthesis of Na+ (in) channels & K+ (out) channels in apical membrane. increase Na+/K+ 3:2 ATPase in basolateral membrane
How does Aldosterone effect the pH of urine?
makes urine more acidic and plasma more alkaline (increase expression of H+-ATPase and Cl-/HCO3 exchanger of intercalated cells)
What other important areas are receptors for Aldosterone (type I MC steroid receptors) located?
salivary glands, sweat glands (increase Na+ intake), colon (increase K+ excretion)
How does 21-hydroxlase deficiency present? why?
virilization (androgen excess), sodium wasting, accumulation of DHEA & ACTH; no glucocorticoid or mineralocorticord activity (prevent progesterone from forming 11-deoxycorticosterone & prevents 17alpha-hydroxyprogesterone from forming 11-deoxycortisol)
How does 11beta-hydroxlase deficiency present? why?
virilization (androgen excess), salt/water retention, hypertension; has mineralocorticoid activity (accumulation of 11-deoxycortisterone, 11-deoxycortisol, DHEA, ACTH)
What is Cushing Syndrome?
excess ACTH resulting in excess cortisol (can be ACTH dependent or independent based on CRH:ACTH)
What is Addison Disease?
glucocorticoid & mineralocorticoid deficiency (can see regular mineralocorticoid b/c it can be stimulated by angiotension II/K+)
What is Conn Syndrome?
tumor of adrenal gland causes hypersecretion of aldosterone (hypertension, hypokalemia)
What causes secondary hyperaldosteronism?
excess renin-angiotensin system stimulation of aldosterone
What is Pseudohyperaldosteronism?
activation of type I steroid hormone receptor (mineralocorticoid) by other substances (e.g. glucorticoid resistance)
What is Primary Hypoaldosteronism?
adrenal cannot produce aldosterone; see elevated renin activity
What is Secondary Hypoaldosteronism?
inadequate stimulation by angiotensin II (usually associated with renal insufficiency
What is Pseudohypoaldosteronism?
unresponsiveness of steroid receptor I to mineralocorticoid hormones (sever salt wasting, hyperkalemia, metabolic acidosis)
What substance stimulates the adrenal medulla?
acetylcholine
What kind of cells is the adrenal medulla made of?
Chrommafin Cells (aka pheochromocytes)
How is Epinephrine formed?
Tyrosine –> DOPA (via tyrosine hydroxylase). –> Dopamine (via dopa decarboxylase) –> Norepinephrine (via dopamine-beta-hydroxylase) –> Epinephrine (via phenylethanolamine N-methyltransferase)
What are catecholamines metabolized by? What do they become for excretion?
COMT (cathol-o-methyltransferase) & MAO (monoamine oxidase), excreted as VMA (vanillylmandelic acid)
What types of receptors do catecholamines bind to?
alpha/beta adrenergic G protein-coupled receptors
What type of receptor are alpha adrenergic receptors? What do they have a high affinity for?
Gq, epinephrine
What type of receptor are beta adrenergic receptors? What do they have a high affinity for?
Gs, isoproterenol (asynthetic agonist)
What important role does the beta adrenergic receptor play in the heart?
increase contractility
What receptors does Isoproterenol target?
B1-adrenergic receptor
What receptors do bronchodilators target?
B2-adrenergic receptor
