Nuclear Receptors

Question 1

What are steroid hormones synthesized from?

Answer 1

cholesterol

Question 2

Glucocorticoids, mineralcoritcoids, androgens, estrogens, progesterone are examples of what

Answer 2

steroid hormones

Question 3

what keeps glucocorticoid receptor (GR) in the cytoplasm when inactive

Answer 3

bound to heat shock protein

Question 4

what happens to glucocorticoid receptor when hormone binds?

Answer 4

• heat shock proteins release it
• reveals nuclear localization signal
• receptor dimerizes and translocates to the nucleus
• binding to DNA palindromic sequences called hormone response elements (HREs)
• transcriptional regulation

Question 5

hormone response elements; what element is involved

Answer 5

palindromic DNA sequences that highly conserved protein sequences interact with that regulate transcription. Zinv is involved

Question 6

Net result of glucocorticoid receptor activation

Answer 6

transcriptional activation or repression

Question 7

difference between primary and secondary responses induced by activation of a nuclear hormone receptor

Answer 7

primary–receptor-steroid-hormone complexes activate primary response genes
secondary–the primary response proteins (from primary response genes) turns on secondary response genes

Question 8

difference between glucocorticoid receptors and estrogen receptors?

Answer 8

glucocorticoid are in cytoplasm and then need to get translocated to nucleus whereas estrogen is inside the nucleus already

Question 9

SERMs (selective estrogen receptor modulators)

Answer 9

ligands that have specificity for estrogen receptors in different tissues
-cause estrogen receptors to interact differently with various tissue-specific co-activators and co-repressors

Question 10

steroid receptor antagonists

Answer 10

• they have a high affinity for steroid receptors

- prevent steroid receptors from interacting with HREs

Question 11

tamoxifen

Answer 11

ER antagonist at breast

-tumor growth-arrest, induces apoptosis

Question 12

raloxifene

Answer 12

ER antagonist at breast and uterus

-agonist at bone

Question 13

Can steroid hormones activated differently in different tissues?

Answer 13

Yes, they can be agonists in one tissue and antagonists in another

Question 14

ER alpha and ER beta

Answer 14

estrogen receptors

Question 15

what do ER alpha and beta interact with

Answer 15

possibly g-protein coupled receptor GPR30

-activates growth factor receptors, protein kinases (PIK3), and AKT

Question 16

Non-steroid nuclear hormone receptors

Answer 16

RXR, RAR, TR, VDR, PPAR

Question 17

Difference in consensus sequences of DNA response elements in steroid hormone receptors versus nuclear hormone receptors

Answer 17

steroid=palindromic

other nuclear=direct repeats

Question 18

DNA binding configuration difference in steroid versus nuclear

Answer 18

steroid=homodimer

other nuclear=heterodimer

Question 19

Retinoid X Receptor (RXR) claim to fame

Answer 19

most common dimerization partner for other nuclear receptors

Question 20

what happens when ligand binds to nuclear receptors via direct repeat DNA sequences

Answer 20

• -corepressors dissociate

- -coactivators associate

Question 21

what are corepressors doing and how

Answer 21

keeping gene expression turned off by deacetylation of nucleosome (keeps DNA tightly wound)

Question 22

what are coactivators doing and how

Answer 22

turning on gene expression by acetylating nucleosome

Question 23

PPAR ligands

Answer 23

PPs: toxins, anti-diabetic drugs like TZDs, hypolipidemic drugs, fatty acids and eicosanoids

Question 24

PPAR roles

Answer 24

• most imp=glucose utilization and cholesterol uptake

- also, metabolism of toxins and hepatocarcinoma, macrophage differentiation, anti-inflammatory response

Question 25

TZD activation pathway; what are TZDs used for

Answer 25

• activates PPARy which was dimerized with RXR

- TZDs used for treatment of type 2 diabetes for their ability to sensitize target tissues to action of insulin

Question 26

PPARy

Answer 26

• key TF in adipocyte differentiation

- increases transcription of genes involved in lipid metabolism and energy balance