Steroid Hormones Flashcards
5 classes of steroids (hormone they make)
P-GAME
- progestin (progesterone)
- glucocorticoids (cortisol)
- androgens (DHT, testosterone dihydrotestosterone)
- mineralcorticoids (aldo)
- estrogen (estradiol 17β)
Steroid hormones enter target cells and bind to ___
intracellular receptors, members of the nuclear hormone receptor family
How are steroid hormones transported in the blood?
With a binding/transport protein–usually binding globulins made by liver
location of CYP family
inner mitochondrial membrane and SER
general action of CYP family
- usually add hydroxyl group
- CYP11A1 also has second function where adds ketone C=O
mono-oxygenases requiring molecular oxygen and NADPH
CYP enzyme family
3βHSD family location and action
- located in smooth ER
- catalyzes the flip of the double bone from carbons 5-6 (D5) to 4-5 (D4)
- all bioactive steroids must undergo this reaction
17βHSD (hydroxysteroid dehydrogenase)
important for adnrogens and estrogens
- reduce keton group to hydroxyl
- located in SER
Steroidogenic enzymes display what type of expression
cell type-specific
steroidogenic cells can synthesize cholesterol from ___
acetate
Steroidogenic cells can import cholesterol as ____ via ___ or as ___ via ____
LDL via LDLR mediated endocytosis
HDL via SR-B1
Steroidogenic cells can store cholesterol as ____ using the enzyme ____ and release free cholesterol via _____
cholesterol esters using ACAT (acylaCoA:cholesterol acyl transferase)
free cholesterol via HSL
All steroidogenic cells are able to catalyze the first two reactions common to steroidogenic pathways. What are these two steps catalyzed by?
- CYP11A1
- 3βHSD
Since CYp11A1 is located on the ____, a specific transfer protein is required to get free cholesterol from the cytoplasm to this location. What is the major protein involved?
- inner mitochondrial membrane
- Steroidogenic Acute Regulatory Protein (StAR)
Lipid congenital adrenal hyperplasia
mutation in StAR
Type 1 3βHSD is found in _____ while Type II in ____
Type 1- skin and placenta
Type II- steroidogenic glands
Hypothalamus-Pituitary-Adrenal Cortex Axis
Hypothalamus –> CRH –> corticotropes –> ACTH –> Adrenal Cortex –> Cortisol
CRH=corticotropin-releasing hormone
ACTH= adrenalcorticotropic hormone
Production of steroid hormones that are not in endocrine axes (3)
- aldosterone
- placental steroid hormons
- neurosteroids
Rapid response of ACTH
increase CE –> FC
-Tropic hormones increase their release of cholesterol from lipid droplets, transfer FC into mitochondria, increase StAR so that CYP11A1 can generate P5
Medium response of ACTH
- increase steroidogenic enzymes
- increase synthesis of steroidogenic hormones
- increase synthesis of LDL-R and SR-B1
Long term response
Increased growth of steroidogenic gland (hyperplasia and hypertrophy)
When steroid hormones pass through the cell membrane, they can reside in the cytoplasm tethered to a _____ or may reside in the ____
- chaperone protein (HSP90)
- nucleus
Steroid hormone-receptor complex binds to ____ and recruits ____
specific DNA sequences (often as a dimer) and recruits co-regulatory proteins
can increase/decrease transcription of neighboring gene, altering chromatin structure
about 2/3 of newly diagnosed invasive breast cancer express ____ and are dependent on ____ for their growth
estrogen receptor a (ERa)
estradiol
If the tumor is ER-positive, it will likely respond to the mixed ER agonist/antagonist, _____
tamoxifen (agonist/antagonist for the receptor)
it binds, and thus prevents estrogen from binding to the receptor, hence breast cancer cell growth is blocked
