Chapter 19 Flashcards
What are the 2 broad groups that hormones are divided into? Give examples from each group. Describe how receptors differ for hormones in the two groups.
Steroidal and non-steroidal.
NS - usually require cell-membrane localized receptors to activate 2nd messenger mols such as cAMP to cause their effects.
ex: broadly include amino acids, peptides etc
S - bind directly at their intracellular receptor for effect
ex: pred, estrogen, androgen, progestins, mineralocorticoids
estrogen and testoterone are made from what common precursor?
cholesterol
androgens are primarily made in what cells in the body? they also come from what gland?
leydig cells in testes
adrenal gland
in the prostate, testosterone is changed to dihydrotestosterone by what enzyme?
which hormone (of the 2 mentioned here) is more potent?
in humans, the enzyme mentioned here can be inhibited by what drug?
5 alpha reductase
DHT
finasteride (inhibitor of 5 alpha reductase) AKA propecia
what chromosome is the androgen receptor located on?
what group is most susceptible to mutations on this chromosome bc of its location?
x chromosome
men bc they only have 1 allele
Quantification of estrogen and progesterone receptors has been done in dog mammary tumors. did this study show any effect of the presence or absence of these receptors on outcome in these patients?
Yes ER and PR + do better
similar in people
what mutated gene in humans can be inherited and stronly associated w/ risk of developing breast cancer
brca 1 and 2
name at least 1 protein overexpressed in human mammary tumors that lead to progresson of malignancy by stimulating the cell cycle
Her 2 (neu-erbB-2),
Cyclin D1
Also inactivation of p53
what does PIN stand for in prostate cancer
what is the sigificance of PIN
prostatic intraepithelial neoplasia
it is a pre-invasive pre-cancerous lesion found in ducts and acini of the prostate
does not penetrate the basement membrane
for ER+ tumors, anti-estrogen therapy is one form of treatment. name 2 broad mechanisms for inhibiting estrogen and then give more specific examples of each
1st - reducing estrogen levels via oophorectomy or LHRH agonists, aromatase inhibitors
2nd - blocking estrogen action at the ER
TAMOXIFEN - nonsteroidal anti-estrogen for use against ER or PR positive breast cancer; acts as a competitive inhibitor for binding at ER. Can have estrogenic effects and anti-estrogenic effects depending on target organ. ex: estrogenic on bone, CV tissues and uterus. the latter can be detrimental since it can lead to growth of uterine tumors. also in group of drugs called SERMs, selective estrogen receptor modulators.
FULVESTRANT - steroidal anti-estrogen. has little estrogenic activity. works by inreasing ER degradation.
how could ketoconazole be used to treat hormone responsive tumors?
inhibits steroid synthesis in general
name 2+ mechs of resistance to tamoxifen therapy
1 - there may be a group of cells from the start that are hormone independent and as tamoxifen kills dependent cells these cells are selected to survive and become the predominant type
2 - epigenetic changes
3 - altered uptake and metabolism of tamoxifen
4 - gene amplification of the androgen receptor
5 - altered receptor structure
6 - altered co-regulator activity; upregulation of antiapoptotic genes such as bcl-2
define SERM. the ideal SERM would have what characteristics?
Selective estrogen receptor modulator
Positive estrogenic effects on bone and other tissues
anti-estrogenic effects on uterus, breast and clotting system
what are the reported toxicities of tamoxifen in dogs
diarrhea
anorexia
reversible neurotoxicity
UTI, stump pyo, signs of estrus, vulvar d/c, swelling, incontinence
owners lack of compliance dt estrogenic effects
