Week 3: Signal transduction I Flashcards
What are strategies for eliminating growth promoting signals from hormones?
1) Remove hormone producing organ
2) Lower concentration of hormone in the blood
3) Block the ability of the hormone to interact with its receptor
4) Block the down-stream signaling between receptor and the effector apparatus
What are ways to lower hormone concentration?
Decrease synthesis (turn down synthesis stimulus, direct drug-based inhibition), Increase catabolism, Use neutralizing antibody to “soak up” all the hormone
What is the LHRH axis?
Hypothalamus releases LHRH stimulating the pituitary gland to release LH/FSH, which then stimulates the testis to release testosterone that stimulates prostate growth
What are ways to decrease testosterone?
1) Remove testicles, 2) remove testicles and adrenals, 3) Remove pituitary, 4) Use LHRH antagonist, 5) Use LHRH super agonist, 6) use LH antagonist, 7) Use an inhibitor of steroid biosynthesis, 8) Use a neutralizing antibody
Why do LHRH analogs (leuprolide, Goserelin) contain D- configurations instead of “L” configurations of amino acids?
Proteases can only attach and breakdown L amino acids, D configurations allow the drugs to stay around much longer
What is the biological idea behind superagonists?
Binding strongly to LHRH receptors, this stimulates an initial increase in LH and Test, but they will fall due to receptor down-regulation
What are the long term side effects of LHRH superagonists (leuprolide, goserelin)?
Iatrogenic osteoporosis, worsening insulin resistance and affective disorders in up to 30%
What is the effect of direct drug-based inhibition of lowering testosterone?
Can lower levels of cortisol, depending on which enzyme you target (17-layase inhibition)
How do you directly block testosterone
block conversion of testosterone into DHT via 5-alpha-reductase, and block androgen receptors, block the down-stream signaling between the receptor and effector apparatus
Give two examples of anti-androgens?
bicalutamide, enzalutamide
T/F: Leuprolide is effective in treating breast cancer
True
What are side effects of aromatase inhibitors?
arthralgia and myalgia in about 20% of patients
What are 2 aromatase inhibitors?
anastrozole, exemestane
What class of drug is tamoxifen?
Selective estrogen receptor modulator
Why can tamoxifen be used to treat breast cancers but not have side effects on bones? What other cancer can it cause?
It is a receptor antagonist in breast, but an agonist in bone and uterus; can cause endometrial cancer
