adrenal physiology

Question 1

Function of adrenal cortex

Answer 1

secretes steroid hormones: mineralcorticoids (aldosterone), glucocorticoids (cortisol), and sex steroids

Question 2

Which part of the adrenal cortex secretes mineralcorticoids

Answer 2

zona glomerulosa (outer)

Question 3

Which part of the adrenal cortex secretes glucocorticoids

Answer 3

zona fasciculata (middle)

Question 4

Which part of the adrenal cortex secretes sex hormones

Answer 4

zona reticularis (inner)

Question 5

What is the fetal zone

Answer 5

a region in the inner zone which is only present during fetal life and serves as an important source of precursor for estrogen synthesis by the placenta

Question 6

1. Identify the key steps in steroid hormone biosynthesis.

Answer 6

circulating LDL > release of Cholesterol by removal of esters (inside cell) > pregnenolone (20,22 desmolase in mitochondria)

Question 7

compare enzymes in different regions of the adrenal cortex

Answer 7

All zones contain desmolase. Zona glomerulosa lacks 17a-hydroxylase and so cannot make glucocorticoids or sex steroids. Inner zone has high activity of 11B-hydroxylase required for cortisol synthesis

Question 8

21-hydroxylase deficiency

Answer 8

Congenital defect in 21-hydroxylase, which is required for the conversion of 17-hydroxyprogesterone and progesterone to the precursors of cortisol and aldosterone, 11-deoxycortisol and 11-deoxycorticosterone, respectively. Cortisol and aldosterone are not produced, adrenal androgens increases

Question 9

Cortisol structure

Answer 9

has ketones at carbons 3 and 20 and hydroxyls on carbons 11, 17 and 21

Question 10

2. Describe the transport of glucocorticoids in the plasma.

Answer 10

Cortisol circulates primarily (90%) bound to proteins. Only 10% circulates in a free form. Of the 90% that is bound, 75% is bound to cortisol binding globulin (CBG) and 15% is bound to albumin.

Question 11

Benefits of cortisol protein binding

Answer 11

increases the plasma concentration of hormone, prevents its excretion by the kidney, prolongs its half-life and serves as a reservoir of extra hormone. If the binding protein is elevated, the total concentration of hormone in the plasma is elevated but the biological activity of the hormone is unchanged, because it is the concentration of free hormone (set point) that is regulated

Question 12

Actions of glucocorticoids

Answer 12

1. glucose mobilization. 2. lipolysis and deposition of adipose tissue on trunk, abd, face and mobilization from extremities. 3. Excretion of water (cortisol inhibits ADH). 4. Gastric acid secretion. 5. stimulates synthesis of phenyl-N-methyl Transferase (PNMT) thus increasing the production of epinephrine from norepinephrine. 6. Anti-inflammatory/ immunosuppressants

Question 13

How do glucocorticoids mobilize glucose

Answer 13

1. stimulation of gluconeogenesis in the liver. 2. Increased proteolysis in muscle and other soft tissues providing amino acid substrates for gluconeogenesis.

Question 14

Negative affects of high levels of cortisol

Answer 14

Catabolic actions: Muscle weakness, thinning of the skin and increased capillary fragility leading to easy bruisability. Also interfere with calcium absorption and/or bone formation, so that osteoporosis and bone fractures are a common side effect

Question 15

List synthetic glucocorticoids

Answer 15

Dexamethasone (powerful), Prednisone, triamcinolone, hydrocortisone.

Question 16

Which synthetic glucocorticoids can be used in Addisons disease

Answer 16

Hydrocortisone and prednisone also have considerable mineralocorticoid potency and can be used in cases of Addison’s disease where both gluococorticoid and mineralocorticoid secretions are compromised

Question 17

4. Diagram the regulation of ACTH production and release.

Answer 17

CRH (hypothalamus) > ACH (ant. Pituitary) > cortisol (zona fasciculata) > cortisol negatively feedsback on hypothalamus and pituitary to inhibit CRH and ACTH secretion

Question 18

How does ACTH increase cortisol secretion

Answer 18

In the cortex, ACTH leads to elevated cAMP levels, which in turn increase the rate of synthesis of pregnenolone. LDL uptake is also enhanced, as is hydrolysis of stored cholesterol esters and transport of cholesterol into mitochondria

Question 19

Cortisol fluctuation thorughout the day

Answer 19

Elevated at time of waking in morning and decreased at the onset of sleep

Question 20

How does stress affect cortisol

Answer 20

Stress can override cortisols negative feedback on CRH and ACTH resulting in up to a 40-fold increase in cortisol secretion. Individuals who are not able to respond to stress with increased cortisol secretion have increased morbidity.

Question 21

Adrenal androgen regulation

Answer 21

Adrenal androgens are stimulated by ACTH

Question 22

Regulation of mineralcorticoid secretion

Answer 22

Aldosterone is regulated by the renin-angiotensin system. It is only minimally influenced by ACTH. Decreased plasma volume or sodium OR BP > Renin release (juxtaglomerular apparatus of kidney) > renin converts angiotensinogen to angiotensin 1 > degraded to angiotensin II > stimulates aldosterone secretion

Question 23

Actions of aldosterone

Answer 23

stimulate sodium absorption, potassium, and hydrogen ion excretion in the renal tubule. Also spares sodium in sweat glands in hot, humid environments

Question 24

Metabolism of steroid hormones

Answer 24

they undergo reactions in the liver that tend to both reduce their activity and increase their water solubility. The metabolites are then excreted in the urine providing a convenient medium for assessing their secretion

Question 25

Primary adrenal insufficiency

Answer 25

Aka Addisons disease: an infectious process (e.g., tuberculosis, fungal disorders, autoimmune response) wipes out the entire adrenal cortex. It is life threatening and both mineralocorticod and glucocorticoid secretion is deficient. Symptoms include weakness, weight loss, hyponatremia, hyperkalemia, GI problems. ACTH is not subjected to negative feedback and it is elevated leading to hyperpigmentation. Glucocorticoid and mineralocorticoid activities must be replaced.

Question 26

Secondary adrenal insufficiency

Answer 26

Due to ACTH insufficiency. Only glucocorticoids need to be replaced. It usually occurs as a general defect in the anterior pituitary (panhypopituitarism).

Question 27

Hyperaldosteronism

Answer 27

Increased plasma aldosterone can result from a tumor of the adrenal cortex (primary) or inappropriately high activity of the renin-angiotensin system (secondary). Symptoms include hypertension in the case of primary hyperaldosteronism, hypokalemia, and alkalosis.

Question 28

Congenital adrenal hyperplasia

Answer 28

Congential defects in the 21-hydroxylase or 11b-hydroxylase pathways of steroidogenesis decrease the synthesis of adrenal corticoids so that the negative feedback pathway controlling ACTH release is defective. The resultant increased ACTH stimulates steroidogenesis and precursors accumulate as well as hormones whose synthesis is not affected (e.g. adrenal androgens in some cases). In females, a common symptom is masculinization.

Question 29

Cushings Sydrome

Answer 29

Excessive secretion or levels of cortisol. Central obesity, moon facies, dorsocervical fat deposits, and supraclavicular deposits. Hirsutism, thinning of skin with purple striae, easy bruising, slow wound healing. Muscle weakness, osteoporosis, insomnia, depression

Question 30

What is the adrenal medulla derived from

Answer 30

neural crest- it is a specialized sympathetic ganglion.

Question 31

Adrenal medulla structure

Answer 31

Contain cells called adrenal chromaffin cells which are stimulated by nerve endings of cholinergic preganglionic fibers of SNS

Question 32

Function of adrenal medulla

Answer 32

Ach from cholinergic preganglionic cells act on cholingergic receptors on chromaffin cells to release the catecholamine hormone epinephrine, and to a lesser extent, norepinephrine (NE). Ca dependent exocytosis

Question 33

Synthesis of epi and NE

Answer 33

Rate limiting enzyme in chromaffin cells is tyrosine hydroxylase, a cytosolic enzyme that converts tyrosine to dihydroxyphenylalanine > converted to dopamine > taken up in secretory granules and coverted to NE then epi

Question 34

compare alpha and beta adrenergic receptors G proteins

Answer 34

Beta: Gs, stimulates adenylate cyclase and cAMP. Alpha1: Gq, PLC pathway. Alpha2: Gi/o, inhibits cAMP production

Question 35

compare epi and NE activation of adrenergic receptors

Answer 35

epi: Beta > alpha. NE: alpha > Beta (no Beta 2)

Question 36

What stimulates release of epinephrine

Answer 36

Perception or even anticipation of danger, trauma, pain, and other physiological stressors like hypovolemia, hypotension, hypoglycemia, and exercise. Final common pathway is activation of cholinergic fibers in greater splanchnic nerve. Activaion of nicotinic acetylcholine receptors (nAChRs) (and possibly muscarinic acetylcholine receptors (mAChRs)) leads to release of catecholamines

Question 37

7. Describe the body’s integrated response to stress.

Answer 37

Stres causes release of CRH, ADH and NE in hypothalamus. NE mediates arousal, aggressiveness, sharpening of sensory behaviors. CRH activates the ACTH-crtisol axis. Also stimulation of sympathetic neurons in hypothalamus leads to stimulation of splanchnic nerve and release of epi from adrenal medulla. epi and cortisol lead to energy mobilization, cardiac responsiveness.