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15 Cards in this Set
- Front
- Back
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How do hormones get through the PM or nuclear membrane to act on nuclear receptors?
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Hormones are lipophilic (hydrophobic) - they can diffuse through membranes with ease.
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How many types of nuclear receptors are there?
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2 types- type 1 and type 2.
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Type 1 signaling - where do the receptors live? How do they exist before being activated?
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They live in the cytoplasm, bound to HSP 70 to keep them inactivated.
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In type 1 signaling, what happens after hormone binds? what does it bind to in the DNA? what does it then recruit?
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displaces HSP 70 at the Ligand Binding Domain (LBD).
receptor now HOMO-dimerizes and passes through the nuclear membrane. binds INVERTED repeat sequence segments. recruits HAT and SWI/SNF to unfold DNA and up transcription. |
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What kinds of hormones act through type 1 signaling?
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estrogens/androgens
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type 2 signaling - what does the inactive state look like? where does it live?
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lives in nucleus, not in cytosol.
normal state is REPRESSION - no homodimerization, basal state is HETERO-dimerization with RXR (retenoid X receptor) - binds corepressors (HDAC) to suppress genes. |
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Type 2 signaling - what happens after binding of ligand?
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binding of ligands displaces corepressors, brings in coactivators (hat swi/snf), activate target genes.
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nuclear receptors - what kind of TF are they?
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think zinc fingers.
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Estrogen receptor - what drug is an antagonist? How does it work? What's another organ that may be affected, and how?
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Tamoxifen - in the breast, tamoxifen results in recruitment of corepressors, decrease growth.
In endometrium in utetrus, tamoxifen has opposite effects - recruits coactivators to promote growth, increase risk of uterine cancer. |
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In the prostate, what kind type of nuclear regulator do we have (1 or 2?)
what activates it? |
Type 1 activation by androgens. Causes up in PSA, up in growth, up in cell survival.
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What type of therapy can be used in prostate cancer? What are the drug names?
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Androgen ablation. LHRH antagonists (Lupron and Zoladex) and anti-androgens from the adrenals (Flutamide or Casodex)
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After therapy, what kind of cancer can develop later on?
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Hormone refractory cancer - 5 types. Can use other activation pathways (crosstalk), receptor mutations (use other activators). receptor overexpression, other oncogenic pathways.
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What drugs can then be used?
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Herceptin (ihibit receptor signaling) or apoptotic peptides
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Type 1 - what class of hormones should we think of?
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Androgens/Estrogens/Glucocorticoids
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Type 2 - what kinds of signals?
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Vitamin D, retenoids, thyroid, orphans
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