Cholesterol & Steroid Metabolism

Question 1

SLOS:
Smith‐Lemli‐Opitz
Syndrome

Answer 1

Autosomal Recessive

microencephaly
embryonic malformations
surviving children have an IQ of
20‐40

partial deficiency of 7‐
dehydrocholesterol reductase:
needed for the correct double‐
bond formation in ring B to make
a complete cholesterol structure

Question 2

Cholelithiasis

Answer 2

Bile Salt Deficiency
Lecithin Deficiency

cholesterol precipitates in the
gall bladder

possible causes:
-malabsorption of bile acids from
the intestine
-obstruction of biliary tract
interruption of enterohepatic
circulation
-decreased bile production
(hepatic dysfunction)
-accelerated rate of bile recycling
(excessive suppression of bile
synthesis)

Treatment
-surgical removal of gall bladder
-chenodeoxycholic acid (chenodiol)
-disintegration of bile stones by
shock waves
-dissolution w/ methyl‐tert‐
butyl ether

Question 3

Acute Pancreatitis

Answer 3

pancreatic amylase and lipase in
the serum

caused by migrating gallstones
that obstruct the ampulla of Vater

Question 4

Adreno‐Cortico‐Tropic

Hormone (ACTH)

Answer 4

aka: corticotropin
release is stimulated by
corticotropin releasing hormone
(CRH) from the hypothalamus

pituitary gland

stress hormone that stimulates
hormone synthesis
(glucocorticoids) in the adrenal
cortex: stimulates synthesis and
release of cortisol

cortisol is the feedback inhibitor for
ACTH release

Question 5

Cortisol

Answer 5

Hormone: Dominant
Glucocorticoid

• synthesized from progesterone in the zona fasciculata of the adrenal cortex
• stress adaptation
• elevates blood pressure
• elevates Na+ uptake
• immune system effects
• anti‐inflammatory

-needed in the liver for gluconeogenesis (especially during prolonged starvation)
-degradation of muscle protein
(counteracts insulin, which leads to muscle protein synthesis)
-inhibition of stimulated phospholipase A2
-inhibits induction of COX‐2

Question 6

Aldosterone

Answer 6

Hormone: Dominant Mineralcorticoid

• produced from progesterone in the zona glomerulosa of the adrenal cortex stimulates renal reabsorption of Na+ and excretion of K+
• elevates blood pressure

-stimulated by angiotensin II/III
ACTH stimulates aldosterone
synthesis

Question 7

Estrogen

Answer 7

-control menstrual cycle
-promote development of female
secondary sex characteristics

stimulated by FSH

Question 8

Progesterone

Answer 8

-secretory phase of uterus and
mammary glands
-implantation and maturation of
fertilized ovum

-stimulated by LH
-produced directly from
pregnenolone and secreted from
the corpus luteum

Question 9

Estradiol

Answer 9

produced in the ovary

secondary female sex
characteristics

stimulated by FSH

Question 10

Androgens:
Dehydroepiandrosterone
Androstenedione
Testosterone

Answer 10

• stimulates spermatogenesis
• promotes development of male
• secondary sex characteristics
• promotes anabolism
• masculinization of the fetus

-produced by the adrenal z.
reticularis and z. fasciculata
-testosterone is synthesized in the
testes, produced from
progesterone
-stimulated by LH

Question 11

17‐a‐hydroxylase/ CYP 17A1/ P450c17 deficiency

Answer 11

• female‐like genitalia
• Na+ and fluid retention
• hypertension

build up of progesterone

• virtually no sex hormones or cortisol
• increased production of mineralcorticoids

Question 12

21‐a‐hydroxylase/ CYP 21A2/ P450c21 deficiency

Answer 12

• most common form
• masculinization of external genitalia in females and early virilization in males

build up of 17‐a‐
hydroxyprogesterone

-partially and virtually complete deficiencies are known
-mineralcorticoids and
glucocorticoids are virtually
absent (classic form) or deficient
(non‐classic form)

Question 13

11‐B‐hydroxylase/ CYP11B/ P450c11 deficiency

Answer 13

• fluid retention
• low‐renin hypertension
• masculinization
• virilization

build up of 11‐deoxycorticosterone

• decrease in serum cortisol, aldosterone, corticosterone
• increased production of deoxycorticosterone causes fluid retention
• hormone supresses renin/angiotensin system

Question 14

3-B-hydroxysteroid dehydrogenase deficiency

Answer 14

• no glucocorticoids, mineralcorticoids, active androgens, estrogens
• salt excretion in urine
• female like genitilia

Question 15

Cushing’s Syndrome:

Hypercortisolism

Answer 15

Adrenocortical Tumor: Hyperfunction of AdrenalCortex

glucocorticoid excess leads to

• protein loss
• characteristic fat distribution‐‐face, neck, truncus
• hirsutism (abnormal hair growth)
• early pubic hair

Question 16

Addison’s Disease

Answer 16

Primary Adrenal Cortical
Insufficiency

-adrenal cortex atrophy due to disease
-autoimmune destruction
-aldosterone and cortisol levels are low
- ACTH is high, which does not lead
to hyperplasia due to cortex atrophy

failure to thrive
muscle weakness
fatigue
weight loss
hyperpigmentation
salt craving
hyponatremia
hypokalemia
hypovolemia
hypotension
abdominal pain
vomiting
constipation

Question 17

Glucocorticoid Therapy

Answer 17

Drug: Inflammation

-asthma treatment
-anti‐inflammatory
-extended corticosteroid therapy
can lead to cushingoid features‐‐
low ACTH, high cortisol

synthetic glucocorticoid analogues
bind less to transcortin and enter
in large amount in the cells