Steroid Biosynthesis

Question 1

• Short term response by adrenal gland involves _ that release catecholamines (NE and EPI)
• Long term response by adrenal gland involves _ that release glucocorticoids and mineralcorticoids

Answer 1

• Nerve Impulses
• Steroid Hormone Signaling

Question 2

• Steroid hormones are derived from _

Answer 2

• Cholesterol

Question 3

• _ is a precursor to many steroid hormones

Answer 3

• Progesterone

Question 4

• Corticosteroids
• Sex hormones

Answer 4

• Aldosterone and Cortisol
• Testosterone and Estradiol

Question 5

• Before cholesterol is converted to progesterone, it is converted to pregnenolone via _ enzyme
• This enzyme is found in _ tissue
• Catalyzes the first rate limiting step
• _ regulated by ACTH

Answer 5

• Desmolase/CYP11A1/CytochromeP450
• steroid producing (adrenal, testes, ovary, placenta)
• ACTH

Question 6

• ACTH stimulates release of _ from the adrenal cortex
• This feeds back to inhibit CRH release from the hypothalamus and ACTH from the anterior pituitary

Answer 6

• Cortisol

Question 7

• Short term action of ACTH (seconds)

Answer 7

• Stimulates lipoprotein uptake into cortical cells
• Increases bioavailability of cholesterol in the adrenal cortex

Question 8

• What are the long term effects of ACTH (hours)?

Answer 8

• Increased transcription of genes coding for steroidogenic enzymes:
  
  • P450
  • Steroid 11 beta hydroxylase
  • E- transfer proteins

Question 9

• ACTH and Cancer

Answer 9

• In cancer:
  
  • cortisol production is uncoupled from ACTH
  • Stim of ACTH is no longer required to activate PKA and make cortisol

Question 10

• Progesterone
  
  • ​Receptor
  • Action

Answer 10

• Binds and activates Progesterone Receptor
• Gestation support hormone

Question 11

• Cortisol
  
  • ​Receptor
  • Action

Answer 11

• Binds and activates glucocorticoid receptor
• Increaes gluconeogenesis and blood pressure
• Anti-inflammatory (EX: Dexmethasone-GR receptor agonist used to treat inflammation)

Question 12

• Aldosterone
  
  • ​Receptor
  • Action

Answer 12

• Binds and activates mineralcorticoid receptor (MR)
• Increases Na+ and H2O retention
• Raises blood pressure

Synthesized in adrenal glands

Distributed to kidney tubules, colon, and parotid

Increases Na+/H2O retention, K+ excretion and blood pressure

Question 13

• Estradiol
  
  • ​Receptor
  • Action

Answer 13

• Binds and activates estrogen receptor alpha
• Female sex development
• Maintenance of bone structure

Question 14

• Testosterone
  
  • ​Receptor
    Action

Answer 14

• Binds and activates androgen receptor
• Male sex hormone

Synthesized in adrenal glands, ovaries, and testes

Distributed to primary and secondary reproductive organs and muscles

Mediates spermatogenesis, secondary male characteristics, bone maturation, and virilization

Question 15

• Normal term infants versus premature infants and production of glucocorticoids

Answer 15

• Normal term infants:
  
  • Burst of glucocorticoids during delivery stimulates production of surfactant and alters lung structure
• Premature infants:
  
  • Process is defective-can lead to infant respiratory distress syndrome
  • Prevented by giving mother glucocorticoids

Question 16

• Congenital Adrenal Hyperplasia (CAH): Patient Presentation

Answer 16

• Hirsutism-excessive body hair on parts of body where hair is normally absent (chin or chest)
• Females also present with:
  
  • oligomenorrhea-infrequent menstruation
  • Infertility
• Important because baby can be at risk for developing
  
  • Test w/ HLA Ag haplotype
    
    • Will show excess cortisol precursors in amniotic fluid

Question 17

• Classical CAH

Answer 17

• Simple virilizing-ambiguous genitalia in females
• Salt wasting: dehydration, vomiting, diarrhea

Question 18

• Non-Classical CAH

Answer 18

• Milder
• Androgen excess can cause precocious puberty in either sex
• Males often undiagnosed and asymptomatic

Question 19

• Consequences of CAH
• Treatment for CAH

Answer 19

• Life threatining sinus infections
• Life threatening pulmonary infections
• Orthostatic syncope
• Shortened Stature
• Severe Acne

Treat with HRT (hormone replacement therapy)

Question 20

CAH is an _ disease caused by mutations of genes that encode the enzymes of steroidogenesis

Most of these conditions involve excessive or deficient production of sex hormones

Function in adrenal glands during conversion of cholesterol to mineralcorticoids, glucocorticoids, and sex steroids

Answer 20

• Autosomal recessive

Question 21

• 5% of CAH cases are caused by a mutation in _

Answer 21

• 11beta hydroxylase
• Corticosterone precursors build up
• Excess androgen production (male sex hormones)
• 17 alpha hydroxy progesterone accumulation
• HTN
  
  • Accumulation of 11 deoxycortisone and 11 deoxycortisol
  • 11 deoxycorticosterone Receptor MR agonist normally regulated by aldosterone
  • Promotes Na+ and H2O retention
  • Lowers Plasma K+

Question 22

• 90-95% of CAH cases are related to a mutation in _ enzyme

Answer 22

• 21 alpha hydroxylase
  
  • ​Reduced cortisol synthesis
  • Hyperplasia of adrenal cortex
  • Elevated ACTH levels (cortisol isn’t being produced, anterior pituitary makes more ACTH)
• Hormones accumulate abnormally:
  
  • Increased progesterone
  • Increased 17 alpha-hydroxypregnenolone
  • Increased 17 alpha hydroxyprogesterone
• Salt wasting
  
  • Lack of aldosterone (Increased Na+ loss in urine)

Question 23

• Steroid Hormone Blood Transporter Proteins
• Where are these synthesized?

Answer 23

• Corticosteroid binding globulin (GBG)
• Sex steroid binding globulin (SHBG)​
  
  • Partially saturated in women
  • Fully saturated by testosterone in men
• Liver

Question 24

• RAAS

Answer 24

Question 25

* Pregnenolone via \_, \_, and \_, is used to produce other steroid hormones (progesterone, aldosterone, testosterone, estradiol, cortisol)

Answer 25

* CYPs, HSDs, Lyases

Question 26

* More rare forms of CAH are cauesd by _ mutations * Show as altered primary or secondary sex characteristics in infants, children, and adults

Answer 26

* CYP17A1

Question 27

* ***ILD (Isolated 17, 20 Lyase Deficiency)*** * ***​****Rare, _ disorder* * *Complete or partial loss of \_* activity * *Impaired production of _ and _ sex steroids* * *\_* *production is not altered, so there is no adrenal hyperplasia or hypertension* * *Symptoms*

Answer 27

* AR * 17,20 lyase * Androgen and estrogen sex steroids * Cortisol/Aldosterone * Sx in males * Pseudohermaphroditism * Partially or fully underdeveloped genetalia * Intersex * Both sexes sx * Reduced or absent puberty * Lack of dev of secondary sex characteristics * Childlike appearance in adulthood if left untreated

Question 28

* ***Regulation of hormone synthesis in the ovaries and testes*** * ***​Stimulated by \_*** * ***\_ facilitates conversion of androstenedione to estrone and conversion of testosterone to estradiol***

Answer 28

* ACTH * FSH

Question 29

* ***Regulation of steroid hormone synthesis in males and females***

Answer 29

Question 30

* ***Vitamin D production*** * ***​Vitamin D is obtained thru _ or \_*** * ***\_ is formed exclusively in the liver by 25-hydroxylase enzyne encoded by CYP2R1 gene***

Answer 30

* Skin or diet * 25-hydroxycholecalciferol