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Details Title: Female Sex horomones Description: 4.20.07 Total Flash Cards: 49 Created: 04/25/2007 16:26:07	To study from this set of flash cards, or to create your own your own study flash cards, register HERE. If you are already a registered user, CLICK HERE.
Cards Term what are the female sex horomones? Definition progesterone, estrone, 17beta estradiol, and estriol Term what are 2 important enzumes in ovary steriodogenesis? Definition aromatase, and 17beta HSD Term where does steriodogenesis occur? Definition in the graffian follicle, adrenal Term what happens in the corpus luteum? Definition cholesterol is changed into progestone Term what are 2 female sex horomones in the adult? Definition estrogen and progesterone Term is estrogen produced in the follicular phase more than in theluteal phase? Definition in the follicular phase Term progesterone? Definition in the luteal phase Term what are exogenous estrogens? Definition 1. Natural estrogens derived from stallion or pregnant mare a. Estrone b. Estradiol c. Estriol 2. Steriodal synthetic estrogens : a. Ethinyl estradiol b. Mestranol c. Quinestrol 3. Non steroidal synthetic estrogens: a. Diethylstilbestrol b. Dinestrol c. methestrol Term what happens during puberty (9-15yrs)? Definition Puberty 9-15 yrs: Menarche Anovulatory cycles Corpus luteum development Term what happens during fertile life span (15-50) Definition Fertile life span (15-50 yrs): Proliferation of endometrium Withdrawal bleeding Term pregnancy? Definition Pregnancy: Sustained uterine growth Mammary gland development Term menopuase? Definition Menopause: Preceded by anovulatory cycles Vasomotor flashes Withdrawal bleeding ends Term postmenopause? Definition Postmenopause: Maintenance of female sex organs Bone loss Term progesterone production? Definition In non pregnant state needs LH stimulated corpus luteum In pregnant state produced also by the placenta Term what does progesterone do? Definition Promotes progestational proliferation of the endometrium; Prepares endometrium for implantation Inhibits ovulation; Renders uterus refractory to oxytocin until onset of labor; Progesterone has some androgenic activity; Synthetic progestins differ in their androgenic and estrogenic activity Term what does FSH do in the Control of Steroidogenesis in the Ovary ? Definition FSH stimulates Graafian follicle development, which stimulates the estrogen synthesis Term What does LH do in the Control of Steroidogenesis in the Ovary ? Definition LH ruptures follicle and maintains CL. this stimulates progesterone synthesis. Term what does E do in cells? Definition Plasma estrogen (E) diffuses directly into the nucleus, where it binds with nuclear estrogen receptor ®, and initiates protein synthesis and cell proliferation. Term where does ER alpha work? Definition 595 amino acids DES>Tamoxifen>E2 uterus, testis, ovary, pituitary, kidney, adrenal ERaKO female mice are infertile: hypoplastic uteri, hyperemic ovaries, no corpus luteum, low bone density Term where does ER beta work? Definition 467 amino acids Tamoxifen >DES>E2 uterus, testis, ovaries, prostate, lung, bladder, brain ERBKO female mice: sub-fertile; lack efficient ovulatory function; leukemic Term discuss the progesterone receptor? Definition 933 amino acid protein There are 2 PRS: PRA and PRB; PRKO female mice do not ovulate, have hyperplastic uteri and no mammary gland development. PRA null mice show that PRA is required for normal uterine development and ovulation PRB null mice show that PRB is required for mammary gland development and thymic evolution Term name a receptor agonist Definition Natural synthetic estrogens and Natural progestins Term name a receptor antagonist? Definition Antiprogesterone - RU 486 Term name a receptor modulator? Definition selective ER modulator (SERM) tissue specific receptor and intracrine modulator (TRIM) Term Name a synthesis inhibitor? Definition aromatase inhibitors(anti-estrogens) 3b-HSD inhibitors (anti-progestins) Term Give a summary of contraceptive theraputics? Definition Combination pill Agonist (Estrogen + Progesterone) ; Sequential pill Agonist (Estrogen, then E + P); Mini pill Agonist (Progesterone only) ; Long-term depots Agonist (6-Medroxyprogesterone); Long-term injectables Agonist (Norgestrel); Post-coital methods Agonist (Estrogen, or E+P) Term How do you use Estrogen Replacement Therapy (ERT) and Anti-estrogens ? Definition Hypogonadism; Post-partum lactation (inhibition); Post-menopausal estrogen replacement; Selective estrogen receptor modulators (SERMs); Tissue-specific receptor intracrine modulators (TRIM); Anti estrogen - aromastase inhibitor Term What are 3 replacement estrogens? Definition 1. Ethinyl estradiol, mestranol Oral, transdermal, vaginal rings, creams 2. Premarin Hormone mixture prepared from pregnant mare urine numerous estrogenic compounds 3. Diethystilbestrol Synthetic estrogen – limited use in current practice Term what is proven to prevent post-menopausal osteoporosis? Definition exercise and estrogen Term what are the Cardioprotective Effects of Estrogens ? Definition ERT increases HDL and decreases LDL-cholesterol and reduces the oxidation of LDL and HDL; ERT decreases serum fibrinogen, factor VII and plasminogen Activator inhibitor-1 which are procoagulant factors; ERT increases the thickness of the externa and media layers of the carotid artery but delays intima; ERT reduces the formation of angiotensin II; ERT reverses the acetylcholine induced vasoconstriction of the carotid artery Term WHAT ARE OTHER BENEFICIAL OUTCOME MEASURES? Definition REDUCED COLON CANCER AND HIP FRACTURES Term what are the only recommeded uses of estrogen? Definition sT TX for hotflashes, and topical tx for vag dryness Term Why don't use use E for reducing bone loss Definition bc we have 3 less riskier ways of doing this. Term what are examples of antiestrogens? Definition SERMS Selective Estrogen Receptor Modulators; TRIMS Tissue Specific Receptor Intracine Modulators; Aromatase Inhibitors Inhibits synthesis of estrogen Term what is Selective Estrogen Receptor Modulators(SERM)? Definition Goal is to maintain the good effects of ERT on bone (and possibly CVS) and eliminate the bad effects (endometrial and breast cancer) Antagonist or agonist depending upon the tissue and the drug Term what is SERM's MOA? Definition Mechanism of action SERMs bind to ER ER-SERM complex binds to the ERE in nucleus conformation of the complex determines which co-activator or co-repressor will be recruited to the transcription complex menu of co-activators or co-repressors available is tissue specific Term what are 2 examples of SERMS? Definition 1. Tamoxifen suppresses E2 dependent growth of breast cancer an agonist in the uterus, bone, and maybe cvs agonist effects in uterus limit clinical utility in ERT type IV estrogen receptor modulator 2. Raloxifene suppresses E2 dependent growth of breast and uterus agonist in bone changes bone density by +2.4% per year lowers LDL-cholesterol type III estrogen receptor modulator Term What is the MOA of SERM? Definition It is a Type 3-4 antagonist; Ligand binds to R -Complex binds to HRE -Tissue specific co-activator or co-repressor recruited -Gene transcription altered Term how do you treat hormone indepent breat cancer? Definition Mastectomy (partial/radical) + Radiotherapy & chemotherapy Term Tamoxifen in Breast Cancer ? Definition active 4-hydroxy metabolite It is protects against osteoporosis and CVD It is tumoristatic and not tumoricidal Tamoxifen is recommended for 5 years in ER positive pts Term WHAT ARE DISADVANTAGES OF tAMOXIFEN? Definition Tumoristatic and not tumoricidal Tumor flare can occur upon drug discontinuation Long term use controversial due to potential for endometrial cancer It can place selection pressure on E2 independent tumor cells to expand Not a pure anti-estrogen and tumor cells can develop which are dependent on tamoxifen for growth Term WHAT DO Tissue-Specific Receptor and Intracrine Modulators (TRIMs) DO? Definition alter the synthesis of estrogen, change how it binds Term what do TRIMs do? Definition Inhibit tissue-specific enzymes that regulate the amount of ligand available to interact with steroid receptor By reducing the action of key enzymes involed in synthesis of estrogen estrogen sulfatase and 17b-HSD Called selective estrogen receptor modulation Have the same effects as SERMs but with a different mode of action Blocks estrogens effect in breast with no effect in bone Term what does Tibolone act as? Definition -anti-estrogen in breast - estrogen in bone - progestin in endometrium Term what is TRIM's summary of action? Definition Act by inhibiting estrogen sulfatase and estrogenic 17b-HSD in the breast-prevents ligand access to ER Lack of enzyme inhibition in bone-allows ligand access to ER In estrogen-deficiency 3-OH metabolites are estrogenic in bone-selective estrogen receptor activation Delta-4-ene metabolites are progestagenic in endometrium- selective progesterone receptor activation Term what are Estrogen Synthesis InhibitorsAromatase inhibitors? Definition These compounds block the final step in estrogen biosynthesis catalyzed by CYParom enzyme is a heme dependent mixed function oxidase that catalyzes the successive hydroxylation of testosterone to yield E2 Examples include Letrozole, Vorozole, and Arimidex- all used in the treatment of ER positive breast tumors Term what do you use prgestin therapy for? Definition Dysfunctional uterine bleeding; Contraception ; Endometriosis Term what are 3a-Hydroxysteroids? Definition 3a-Hydroxysteroids are Hormonal Modulators of the GABA Receptor Term what is RU486? Definition Progesterone Receptor Type II Antagonist