Nuclear Receptors

Question 1

What determines the specificity of NRs?

Answer 1

• Ligand it binds
• DNA it binds
• Cooperation w/ DNA-bound accessory factors (may be cell-type or tissue specific)
• Recruitment of co-activators or co-repressors

Question 2

Glucocorticoids

Answer 2

• Anti-inflammatory and immunosuppressive function

- How? block transcription of pro-inflammatory genes/agents

Question 3

Physio Effects of Glucocorticoids (4)

Answer 3

• Regulation of carbohydrate, protein and lipid metabolism
• Maintenance of fluid and electrolyte balance
• Preservation of normal function of the cardiovascular system, the immune system, the kidney, skeletal muscle, the endocrine system and the nervous system
• Preservation of organismal homeostasis (inflammation throws you out of homeostasis so respond w/ anti-inflammatory agent)

Question 4

PPAR gamma

Answer 4

• Treatment of Type II Diabetes b/c insulin-sensitizing effects (inc insulin-mediated glucose uptake into adipose and muscle cells) and reduce plasma levels of FAs
• Con- adverse cardio effects

Question 5

TZDs

Answer 5

Synthetic ligands that produce insulin sensitizing effects if bind PPAR gamma
(but also adverse cardio effects)

Question 6

PPAR delta

Answer 6

• Regulates lipid and glucose metabolism
• Inc musc endurance when this receptor is enhanced in mice (“Marathon Mouse”)
• Can also protect against atherosclerosis due to anti-inflammatory effects

Question 7

SERMs Mechanism of Action

Answer 7

• “selective estrogen receptor modulators”
• Target specific estrogen functions in distinct cells as ANTAGONISTS
• Mechanism = recruit co-repressors

Question 8

Tamoxifen

Answer 8

• used in estrogen receptor-positive breast cancer; antagonist of estrogen action in breast (recruits co-repressors) BUT partial agonist (can recruit co-activators) in uterus, liver and bone (can cause uterine cancer)
• AGONIST v ANTAGONIST EFFECT MAY DIFFER BY CELL TYPE OR TISSUE TYPE