Biosynthesis of Steroid Hormones - 10,11 Flashcards
Juxtacrine
direct physical contact
Example: antigen presenting T cells
Endocrine signaling
* ___ in concentration; ___ affinity receptor
* travels ___ distance
Travels through the blood to a target organ expressing receptors.
* minutes to hours
* low; high
* far
Paracrine signaling
* travels ___ distance to affect ___ cells
* fairly high ___ [ ]; receptor with ___ affinity
* ___ and localized communication
- short; nearby
- local; lower
- rapid
Example: cytokines, chemokines
Synaptic or neuronal signaling
* Neurotransmitter; travels very ___ distance.
* Very ___ local concentration; dissociate rapidly.
* Very rapid (___) termination; meant for short duration
- short (synapse size)
- high
- millisecond
Autocrine signaling
* Made and functions in the ___ cell.
* Similar to ___ signaling
- same
- paracrine
Example: Cancer can utilize autocrine to promote their own growth
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 ___
- cholesterol
- tight
- low
- carrier proteins
- transcription
know the numbering system
Steroid hormones
Sex and progestational hormones
* ___ (C-21): female menstrual cycle, pregnancy, embryogenesis
* 17β-Estradiol (C-___): estrogen, female hormone
* ____ (C-19): androgen, male hormone
- Progesterone
- 18
- Testosterone
Steroid receptors are intracellular receptors
Belong to ___ receptor family.
* steroid receptors
* thyroid hormone receptors
* retinoic acid receptor
* vitamin __ receptor
- nuclear
- D
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 ___.
- dimers
- steroid responsive
- transcription
Negative feedback loop
Hypothalamic-pituitary-adrenal (HPA) axis:
* Hypothalamus: ___ →Pituitary gland: ___ → Adrenal gland: ____ → Physiological responses
Negative feedback loop: ____ inhibits both ___ and ___
- Corticotropin releasing hormone (CRH)
- Adrenocorticotropic hormone (ACTH)
- Cortisol
- cortisol, CRH, ACTH
Synthesis of steroid hormones - Universal Steps
Step 1: cholesterol is converted to ____ by the enzyme ____
- pregnenolone
- P450scc (CYP11A1)
What does the “scc” in P4450scc stand for?
side chain cleaving
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) ___
- progesterone
- 21-hydroxylase
- 11β-hydroxylase
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) ___,
- 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
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 ___
- 3β-dehydrogenase-5,4-isomerase
- 1) 17α-hydroxylase
- 2) 17,20 lyase
or
- 1) 17α-hydroxylase
- 2) 17,20 lyase
- androstenedione
- 17β-hydroxysteroid dehydrogenase
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 ____
- 17β-hydroxysteroid dehydrogenase
- aromatase
or
- aromatase
- 17β-hydroxysteroid dehydrogenase
What is this?
Cholesterol
What is this?
Pregnenolone
What is this?
Progesterone
What is this?
Aldosterone
What is this?
Cortisol
What is this?
Dihydroepiandrosterone (DHEA)
What is this?
Androstenedione
What is this?
Testosterone
What is this?
17β-Estradiol
What is this?
Estrone
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 → ___
- hyperplasia (5%)
- CYP17A1
- 17,20-lyase
- mineralcorticoids, corticosteroids
- adrenal glands
- genitalia (intersex)
- hypertension
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)
- adrenal hyperplasia (95%)
- CYP21A2, 21-hydroxylase
- enlargement
- hypoatremia (low sodium levels)
- androgen, early, short
Transport and excretion of steroids
Plasma trasportation
* glucocorticoids and progesterone = corticoid-binding globulin (___)
* testosterone and estradiol = ___ hormone binding ___ (SHBG)
- transcortin
- sex, globulin
Transport and excretion of steroids
- metabolized in the ___ (oxidation, sulfation, and glucuroidation) to ___ forms
- excreted in the _____ (estrogen) or in the urine (____, ___, and ___)
- liver, soluble
- bile, progesterone, androgen, and glucocorticoids
Therapeutic intervention in steroid synthesis
Aminoglutethimide (Cytadren®)
* inhibits ___ and ___
* used to block ___ production in some hormone-dependent tumors (breast, prostate)
- aromatase and P450scc
- steroid
Therapeutic intervention in steroid synthesis
Ketoconazole
* ___ at lower concentration (block synthesis of ____)
* inhibits ___, ___, and ___
* can treat hyperglucocorticoid states (___ syndrome)
* may cause toxic side effects
- antifungal, ergosterol
- P450scc, 17a-hydroxylase, 11B-hydroxylase
- Cushing’s
What is this?
Aminoglutethimide (Cytadren®)
What is this?
Ketoconazole
