Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
31 Cards in this Set
- Front
- Back
List the 5 major classes of hormones and the number of carbons they contain
|
1. progestins-21
2. glucocorticoids-21 3. mineralcorticoids-21 4. androgens-19 5. estrogens-18 |
|
how many carbons does cholesterol have? pregenolone
|
cholesterol=27
pregnenolone=21 |
|
What is the primary target tissue and effect of
glucocorticoids like cortisol, cortisone, corticosterone |
Target= muscle and liver
Effect= protein catabolism, GNG, anti-inflammatory in high doses |
|
What is the primary target tissue and effect of
mineralcorticoids like aldosterone, 11-dexoycorticosterone |
Target=kidney tubules
Effect=sodium retention, Potassium excretion |
|
What is the primary target tissue and effect of
androgen -testosterone |
Target-reproductive organs, muscle
Effect- Spermatogenesis, secondary male characteristics, bone maturation, virilization |
|
What is the primary target tissue and effect of
Estrogens like estradiol and estrone |
Target-reproductive organs
Effect- feminization, cyclic rythms |
|
What is the primary target tissue and effect of
progestin-progesterone |
target= uterus
effect= nidation, maintenance of pregnancy, cyclic rythyms |
|
What are the positive and negative effects of using synthetic androgens as anabolic steroids
|
positive-build muscle mass
negative-kidney, liver, heart problems |
|
where are the steroid hormones synthesized
|
adrenal cortex
|
|
Describe the enzyme that converts cholesterol to prenenolone
|
-desmoalse a cytochrom P450
-localized to matrix side of inner mitochondrial membrane -requires NADPH and O2 |
|
What stimulates the conversion of cholesterol to pregnenolone
|
ACTH synthesized by the anterior pituitary acts on the adrenal cortex
|
|
What is the net reaction of chytochrome P450's
|
RH+O2+NADPH+H+=> ROH +H2O+ NADP+
|
|
Which electron carriers are involved in the mitochondrial steroid hormone synthesis
|
NADPH, adrenodoxin reductase, adrenodoxin, and cytochrome P450
|
|
Where are glucocorticoids (cortisol,cortisone, corticosterone) synthesized
|
Synthesis begins in the mitochondrial where cholesterol is converted to pregnenolone. Pregenenolone is then moved to the ER where is made into 11-deoxycortisol. 11-Deoxycortisol is taken back to the mitochondria where it is converted to cortisol and then exported
|
|
Which electron carriers are used in microsomal (ER) steroid hormone synthesis
|
NADPH, cytochrome P450 reductase, cytochrome P450
|
|
where does the synthesis of mineralcorticoids (aldoesterone) occur?
|
final synthesis occurs in the mitochondrial, 11 hydroxylase, 18hydroxylase, and 18-ol-dehydrogenase are found in the mitochondria
|
|
What is the key enzyme for directing steriods into the synthesis of glucocotricoids, androgens, and estrogens? Where is it found?
|
The key enzyme is 17 hydroxylase which takes pregenonolone to 17-OH-pregenolone and progesterone to 17-OH-progesterone. It is found on the endoplasmic reticulum in steroid secreting organs
|
|
Describe how steroid hormones are degraded
|
-no way to breakdown steroid ring
-partial catabolism and inactivation in liver reduces ketones and double bonds -inactive metabolites are conjugated to glucuronic acid or sulfate and are excreted in the urine |
|
What defect is the most common cause of CAH
|
21 hydroxylase which takes which takes progesterone to 11-deoxycorticosterone and 17-OH progesterone to 11-deoxycortisol
|
|
CAH often involves a deficiency of 21 hydroxylase preventing the synthesis of 11-deoxycorticosterone and 11- deoxycortisol from progesterone and 17-OH progesterone respectivley. What precursors accumulate as a result of this? What products are missing? Which sxs result?
|
-back up in pathway leads to excess progesterone and 17-OH progesterone
-the products are shunted to androgen synthesis leading to virilism -cannot make aldosterone so salt wasting occurs -need to administer glucocorticoids and aldosterone |
|
What is the cause of Addison's disease? How does this develop?
sxs and tx? |
Cause=destruction of adrenal cortex via autoimmune or tuberculous adrenalitis
sxs=fatigue, weakness, weight loss, low BP, hyperpigmentation Tx= replacement therapy with glucocorticoids and aldosterone |
|
What is the cause of Cushing's disease? sxs? Tx?
|
-excessive secretion of corticotropin by anterior pituitary tumors overstimulate the adrenal cortex leading to excess cortisol
-sxs= weight gain, muscle wasting, weakenss -Tx= microadenomectomy, pituitary irradation, adrenalectomy -note sxs mimic by chronic glucocorticoid therapy, stress, depression |
|
Describe the mechanism of action of steroid hormone receptors
|
1. Hormone binds to receptor, induced confirmational change
2. Complex binds as a dimer to HRE in nucleus and recruits general transcription factors and coactivators to form active transcriptional complex 3. results in enchanced gene expression |
|
How does Tamoxifen treat extrogen receptor positive breast cancers (2/3 of breast cancers)
|
Tamoxifen is a synthetic anti-estrogen (SERMs) that functions as an antagonist in breast cancer cells. It binds to the steroid binding domain of the estrogen receptor and induces a confirmational change that prevents coactivators from binding thus preventing transcriptional activation
|
|
Describe the structure of the DNA binding domain of steroid hormone receptors
|
Contain a zinc finger motiff which binds to the HRE sequence in the DNA
|
|
What 4 domains must a steroid hormone receptor contain
|
1. activation
2. DNA bindng 3. hormone binding 4. nuclear localizaiton signal |
|
How are the levels of steroid hormone receptors regulated in the short term compared to the long term
|
short term-directly via HREs, increase transcription within minutes
longer term- indirecty without the HRE, may take hours |
|
which enzyme converts testosterone to DHT
|
5a-reductase
|
|
How does the activity of DHT compare to that of testosterone. How does sensitivity to androgne vary amongst different tissues
|
DHT has a higher affininity for the androgen receptor
The prostate has 2x higher level of androgen receptor than skeletal muscle. This an important consideration for prostate cancer because most are androgen receptor dependent tumors |
|
The majority of prostate cancers are androgen sensitive tumors and the prostate has a much higher levle of androgen receptors than other tumors. How does this concecpt relate to treatment of the cancer
|
Treatment is based on androgen deprivation.
Strategies include; castration (surgical or chemical), inhibtion of steroidogenic enzymes, anti-androgens, inhibtion of 5a-reductase |
|
How doe the steroid hormone synthesis electron carriers differ in the mitochondria and ER
|
mitochondria-NADPH, adrenodoxin reductase, adrenodoxin
ER-NADPH, cytochrome P450 reductase |