88 terms

Wiese: Steroids

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Progesterone

Hydrocortisone

Testosterone

Estrogen
Name the four classes of steroid hormones
Progesterone
What is this structure?
Hydrocortisone
What is this structure?
Testosterone
What is this structure?
17B Estradiol
What is this structure?
b) Testosterone
Which of the following natural steroids is the precursor for 17B estradiol?

a) Progesterone
b) Testosterone
c) Hydrocortisone
e) 17B Estradiol
b) Testosterone
Which of the following natural steroids is the substrate for 5alpha reductase to make DHT?

a) Progesterone
b) Testosterone
c) Hydrocortisone
e) 17B Estradiol
e) 17B Estradiol
The aromatase inhibitor Letrozole reduces the production of which natural steroid below?

) Progesterone
b) Testosterone
c) Hydrocortisone
e) 17B Estradiol
a) True
Estrogens can induce effects on cells through the genomic pathway that involves binding ER and regulating genes as well as through rapid signaling pathways that involve receptors at the cel membrane.

a) True
b) False
Aromatase
What is the key enzyme used to make 17B Estradiol?
Progestins
Implantation/maintenance female sex hormones are known as
b) Phenolic group
The ONE key structure feature required by estrogens to bind ER is (select the most complete answer)

a) Aromatic ring
b) Phenolic group
c) 3-keto group
d) 18-methyl group
e_ 17-OH group
Estrone
What is this structure?
Estrone - 17C ketone group

Estradiol - 17C hydroxy group
What is the significant difference between Estradiol and Estrone?
Estrone
What estrogen binds to the ER 10-100x less than Estradiol?
Androgens
What is needed to make estrogens?
A Pathways which involves the A ring metabolism

B Pathway which involves the D ring metabolism
What are the two pathways of Estrogen metabolism?
Estrogen can undergo phase 1 metabolism producing
2 Hydroxyestrogen and 4 Hydroxyestrogen


Which can then be methylated and eventually progress to Phase II metabolism.
or

The catechol estrogens can undergo oxidation and producing a ketone at the 2 and 4 positions

Both will reactive with purines and undergo depurination producing an AP site


Leading to an increased risk in cancer.
Describe the "A Pathway" of Estrogen Metabolism
This pathway involves the D-ring metabolism

Estradiol undergoes a reversible oxidation to produce Estrone.

Estradiol and Estrone undergoes Hydroxylation at the 16C
Describe the "B Pathway" of Estrogen Metabolism
2-Hydroxyestrogen
What is this structure ?
4-Hydroxyestrogen
What is this structure?
2-Hydroxyestrogen

4-Hydroxyestrogen
What are the two a ring Catechol metabolites of estradiol that may ultimately depurinate DNA.
a) Phase I metabolism
Which of the following involves hydroxylation?

a) Phase I metabolism
b) Phase II metabolism
b) Phase II metabolism
Which of the following involves Sulfonation?

a) Phase I metabolism
b) Phase II metabolism
b) 3,4 Estrogen quinone
Which of the following contain high carcinogenic potential?

a) 2,3 Estrogen quinone
b) 3,4 Estrogen quinone
Depurinated adduct
What is this structure?
Cruciferous veggies
What foods can be consumed in our diet prevent Estrogen metabolism?
Estrone
What is the D ring metabolite of estradiol that can also be reduced back to estradiol?
Methyl
What can be added to the 17C of Estradiol to prevent D-ring metabolism?
Starting with something like estradiol

Adding a substituent to prevent D-ring metabolism
What is the key step in making synthetic estrogens?
Ethinyl Estradiol

(Synthetic Estrogen)
What is this structure?
Ethinyl Estradiol

Estradiol esters
List two types of Synthetic Steroid Estrogens
Ethinyl-Estradiol
What is the most important synthetic long acting estrogen?
Ethinyl estrogens
What synthetic estrogen has the best oral bioavailability due to low D-ring metabolism.

a) True
b) False
Estradiol esters
What synthetic estrogen is most suitable for use as an injectable depot drug?
Premarin
Given an example of a conjugated estrogen
a) True
Premarin is a proprietary mixture of Equilenin, Equilin, and Estrone.

a) True
b) False
Horse urine
Where are Equilenin, Equilin, and Estrone derived from?
Diethylstilbesterol (DES)

Non steroid estrogen
What is this structure?
Estrogen replacement therapy

Prevent Miscarragies
What is DES used for?
DES

(Non-steroid Estrogen)
What is the synthetic estrogen that can cause defects and/or cancer in individuals exposed during development in utero?
DES
What is Tamoxifen derived from?
Genis
What is this structure?
Genistein

(Naturally Occurring Estrogens from Plants; Environmental & Xenoestrogen)
What is this structure?
Bisphenol A

(Environmental & Xenoestrogen)
What is this structure?
Zeranol

(Environmental & Xenoestrogen)
What is this structure?
Methoxychlor

(Environmental & Xenoestrogen)
What is this structure?
Bisphenol A
What is the estrogenic monomer that can leach out of polycarbonate plastics into food?
Genistan
What is the isoflavonoid estrogen found in plants like red clover and soy?
Zeranol
What is the estrogen found in mold and fungi growing on rotten corn?
Tamoxifen
What is this structure?
4-hydroxytamoxifen
What is this structure?
Fluvestrant
What is this structure?
Tamoxifen

Fulvestrant
List two Anti estrogens
Fulvestrant
What is the "pure" anti-estrogen that has no agonist activity and causes degradation of the ER?
Aryl tertiary Amine
Identify what FG directly blocks helix
The Large Function FG
Identify what FG directly blocks helix 12
Fluvestrant
What causes the ER to be Ubiquinated?
4-hydroxytamoxifen
What is the active metabolite of Tamoxifen?
Raloxifene

(SERM)
What is this structure?
d) Both a and b
Which of the following is selective for tissues and genes? S

a) Raloxifene
b) Tamoxifene
c) Fluvestrant
d) Both a and b
Tamoxifen - Direct inhibitor

Raloxifene -Direct inhibitor

Genistein - Indirect inhibitor
What are SERM effects on Estrogen Receptors?
Less activity in the breast and uterus

More activity in the bone
What are the desired features of SERMS?
Anastrozole
(Aromatase Inhibitor)
What is this structure?
Letrozole

(Aromatase Inhibitor)
What is this structure?
Triazole Ring
What FG of Letrozole inhibits the enzyme Aromatase?
False
Non selective because they bind to multiple steps
Steroidal Aromatase Inhibitors are selective

a) True
b) False
a) True
Non steroid Aromatase Inhibitors are selective inhibitors.

a) True
b) False
d) Letrozole
Which of the following is a selective inhibitor of aromatase that binds the catalytic heme in the enzyme?

a) Tamoxifen
b) Raloxifene
c) Fluvestrant
d) Letrozole
Ethinyl groups:
D-ring metabolism inhibitor
C 19:
Bind to PR and Cross react with AR

19-Nor:
Bind to PR selectively;
No AR, 5B reductase (prevent metabolism)

Esters: Lost quickly and do not fit in PR; Pro Drugs
What are the properties of 1st Generation Synthetic Progestins?
Methyl group @ C18:
More PR Activity

19- Nor: S
elective PR

Ethinyl group:
D-ring metabolism inhibitor
What are the properties of 2nd & 3rd generation Synthetic Progestins?
VERY SELECTIVE AND POTENT

Methyl group @ C6:
-inhibit 5-B reductase
-B ring metabolism

19-Nor:
-PR selective

Methyl @ C17
-Prevent D- ring metabolism
What are the properties of 4th generation Synthetic Progestins?
Mifepristone

(Anti-progestin)
What is this structure?
Onapristone

(Anti-progestin)
What is this structure?
RU-486
What is Mifepristone also called?
a) Mifepristone
Which of the following inhibits GR and PR?

a) Mifepristone
b) Onapristone
b) Onapristone
Which of the following inhibits PR only?

a) Mifepristone
b) Onapristone
b) Onapristone
Which of the following reduces metabolism at the D-ring and gives more selectivity?

a) Mifepristone
b) Onapristone
a) True
Mifepristone and Onapristone are Direct antagonists of progestin due to its large FG.

a) True
b) False
5-alpha reductase
What enzyme blocks the synthesis of DHT?
17-alpha inhibitors
What enzyme blocks the synthesis of Testosterone
a) True
Once Testosterone is metabolized it will not have an active molecule

a) True
b) False
Methyl @ C17 alpha

17-OH

Alkyl Ester : makes a nice depot injector
Properties of Synthesis Androgen
Flutamide

(Non steroid Antiandrogen)
What is this structure?
Bicalutamide

(Non steroid Antiandrogen)
What is this structure?
Finasteride
What is this structure?
Dutasteride
What is this structure?
Finasteride

Dutasteride
List two good suicide inhibitors of 5-alpha reductase