Biosynthesis of Steroid Hormones - 10,11

Question 1

Juxtacrine

Answer 1

direct physical contact

Example: antigen presenting T cells

Question 2

Endocrine signaling
* ___ in concentration; ___ affinity receptor
* travels ___ distance

Answer 2

Travels through the blood to a target organ expressing receptors.
* minutes to hours
* low; high
* far

Question 3

Paracrine signaling
* travels ___ distance to affect ___ cells
* fairly high ___ [ ]; receptor with ___ affinity
* ___ and localized communication

Answer 3

• short; nearby
• local; lower
• rapid

Example: cytokines, chemokines

Question 4

Synaptic or neuronal signaling
* Neurotransmitter; travels very ___ distance.
* Very ___ local concentration; dissociate rapidly.
* Very rapid (___) termination; meant for short duration

Answer 4

• short (synapse size)
• high
• millisecond

Question 5

Autocrine signaling
* Made and functions in the ___ cell.
* Similar to ___ signaling

Answer 5

• same
• paracrine

Example: Cancer can utilize autocrine to promote their own growth

Question 6

Steroid hormones

• Synthesized from ____.
• Planar, rigid, and hydrophobic → ___ binding to receptors
• Exist in very ___ concentrations in the body (0.1-10 nM)
• Bound to serum ___.
• regulate ___

Answer 6

• cholesterol
• tight
• low
• carrier proteins
• transcription

Question 7

know the numbering system

Answer 7

Question 8

Steroid hormones

Sex and progestational hormones
* ___ (C-21): female menstrual cycle, pregnancy, embryogenesis
* 17β-Estradiol (C-___): estrogen, female hormone
* ____ (C-19): androgen, male hormone

Answer 8

• Progesterone
• 18
• Testosterone

Question 9

Steroid receptors are intracellular receptors

Belong to ___ receptor family.
* steroid receptors
* thyroid hormone receptors
* retinoic acid receptor
* vitamin __ receptor

Answer 9

• nuclear
• D

Question 10

Hormone response elements

• DNA-binding domains of activated ___ bind to specific DNA sequences called Hormone Responsive Elements (HRE), upstream of ____ genes.
• Binding alters the rate of ___.

Answer 10

• dimers
• steroid responsive
• transcription

Question 11

Negative feedback loop

Hypothalamic-pituitary-adrenal (HPA) axis:
* Hypothalamus: ___ →Pituitary gland: ___ → Adrenal gland: ____ → Physiological responses

Negative feedback loop: ____ inhibits both ___ and ___

Answer 11

• Corticotropin releasing hormone (CRH)
• Adrenocorticotropic hormone (ACTH)
• Cortisol
• cortisol, CRH, ACTH

Question 12

Synthesis of steroid hormones - Universal Steps

Step 1: cholesterol is converted to ____ by the enzyme ____

Answer 12

• pregnenolone
• P450scc (CYP11A1)

Question 13

What does the “scc” in P4450scc stand for?

Answer 13

side chain cleaving

Question 14

Synthesis of steroid hormones - Aldosterone Pathway

Step 2: Pregnenolone can be converted to ___ by 3β-dehydrogenase-5,4-isomerase.

Step 3: progesterone is converted to aldosterone by these enzymes: 1) ____ → 2) ___

Answer 14

• progesterone
• 21-hydroxylase
• 11β-hydroxylase

Question 15

Synthesis of steroid hormones - cortisol pathway

Step 2: Pregnenolone can be converted to ___ by 3β-dehydrogenase-5,4-isomerase.

Step 3: progesterone can be converted to cortisol by these enzymes: 1) ____, 2) ___, 3) ___

or

Step 2: Pregnenolone can be converted to cortisol by these enzymes: 1) ___, 2) ___, 3) ___, 4) ___,

Answer 15

• progesterone
• 1) 17α-hydroxylase
• 2) 21-hydroxylase
• 3) 11β-hydroxylase

or

• 1) 17α-hydroxylase
• 2) 3β-dehydrogenase-5,4-isomerase
• 3) 21-hydroxylase
• 4) 11β-hydroxylase

Question 16

Synthesis of steroid hormones - testosterone pathway

Step 2: Pregnenolone can be converted to progesterone by ___.
Step 3: Progesterone is converted to androstenedione by these enzymes: 1) ___ and 2) ___

or

Step 2: Pregnenolone can be converted to DHEA by these enzymes: 1) ___ and 2) ___
Step 3_ DHEA is then converted to ___ by 3β-dehydrogenase-5,4-isomerase

Step 4: Androstenedione is converted to testosterone by ___

Answer 16

• 3β-dehydrogenase-5,4-isomerase
• 1) 17α-hydroxylase
• 2) 17,20 lyase

or

• 1) 17α-hydroxylase
• 2) 17,20 lyase
• androstenedione
• 17β-hydroxysteroid dehydrogenase

Question 17

Synthesis of steroid hormones - 17β-Estradiol pathway

same steps 2 and 3 as testosterone pathway
Step 4: Androstenedione is converted to testosterone by ___
Step 5: testosterone is converted to 17β-Estradiol by ___

or
Step 4: Androstenedione is converted to Estrone by ___
Step 5: Estrone is converted to 17β-Estradiol by ____

Answer 17

• 17β-hydroxysteroid dehydrogenase
• aromatase

or

• aromatase
• 17β-hydroxysteroid dehydrogenase

Question 18

What is this?

Answer 18

Cholesterol

Question 19

What is this?

Answer 19

Pregnenolone

Question 20

What is this?

Answer 20

Progesterone

Question 21

What is this?

Answer 21

Aldosterone

Question 22

What is this?

Answer 22

Cortisol

Question 23

What is this?

Answer 23

Dihydroepiandrosterone (DHEA)

Question 24

What is this?

Answer 24

Androstenedione

Question 25

What is this?

Answer 25

Testosterone

Question 26

What is this?

Answer 26

17β-Estradiol

Question 27

What is this?

Answer 27

Estrone

Question 28

17α-hydroxylase deficiency

• Rare form of congenital adrenal ____
• Caused by mutations in ___, which has both 17α-hydroxylase and ____ activities.
• Overproduction of ____ and deficiency of ____ and sex hormones.
• Hypocortisolism → enlargement of the ___
• Ambiguous ___
• Hyperaldosteronism → ___

Answer 28

• hyperplasia (5%)
• CYP17A1
• 17,20-lyase
• mineralcorticoids, corticosteroids
• adrenal glands
• genitalia (intersex)
• hypertension

Question 29

21-hydroxylase deficiency

• Major form of congenital ___
• Mutation in ___, which functions as ____
• Hypocortisolism → ___ of the adrenal glands
• Hypoaldosteronism → ___ (can be life-threatening in infants)
• premature ___ exposure which causes hirsutism, ambiguous genitalia in female, and ___ epiphyseal closure (___ stature)

Answer 29

• adrenal hyperplasia (95%)
• CYP21A2, 21-hydroxylase
• enlargement
• hypoatremia (low sodium levels)
• androgen, early, short

Question 30

Transport and excretion of steroids

Plasma trasportation
* glucocorticoids and progesterone = corticoid-binding globulin (___)
* testosterone and estradiol = ___ hormone binding ___ (SHBG)

Answer 30

• transcortin
• sex, globulin

Question 31

Transport and excretion of steroids

• metabolized in the ___ (oxidation, sulfation, and glucuroidation) to ___ forms
• excreted in the _____ (estrogen) or in the urine (____, ___, and ___)

Answer 31

• liver, soluble
• bile, progesterone, androgen, and glucocorticoids

Question 32

Therapeutic intervention in steroid synthesis

Aminoglutethimide (Cytadren®)
* inhibits ___ and ___
* used to block ___ production in some hormone-dependent tumors (breast, prostate)

Answer 32

• aromatase and P450scc
• steroid

Question 33

Therapeutic intervention in steroid synthesis

Ketoconazole
* ___ at lower concentration (block synthesis of ____)
* inhibits ___, ___, and ___
* can treat hyperglucocorticoid states (___ syndrome)
* may cause toxic side effects

Answer 33

• antifungal, ergosterol
• P450scc, 17a-hydroxylase, 11B-hydroxylase
• Cushing’s

Question 34

What is this?

Answer 34

Aminoglutethimide (Cytadren®)

Question 35

What is this?

Answer 35

Ketoconazole