Medicinal Chemistry of Steroids: Estrogens Focus - Steroid Lecture 2 PCOL 826B
40 Questions
5 Views

Choose a study mode

Play Quiz
Study Flashcards
Spaced Repetition
Chat to Lesson

Podcast

Play an AI-generated podcast conversation about this lesson

Questions and Answers

What is the function of tamoxifen in relation to ER-alpha?

  • Inhibits the transcriptional activity of ER-alpha (correct)
  • Enhances the recruitment of co-activators to ER-alpha
  • Induces conformational changes preventing ER-alpha binding to anti-estrogen drugs
  • Activates ER-alpha to bind to estrogen response elements

What is the effect of estradiol versus tamoxifen on ER-alpha?

  • Estradiol is transcriptionally active, while tamoxifen is transcriptionally inactive (correct)
  • Both estradiol and tamoxifen are transcriptionally inactive
  • Estradiol is transcriptionally inactive, while tamoxifen is transcriptionally active
  • Both estradiol and tamoxifen are transcriptionally active

Which compound is a prodrug that requires hepatic O-demethylation to become an active ER ligand?

  • Estradiol
  • Diethylstilbestrol
  • Raloxifene
  • Mestranol (correct)

What is the role of coactivators in ER activation?

<p>Enhance the transcriptional activity of ER by binding to it (B)</p> Signup and view all the answers

Which type of substituent on the D-ring enhances the oral availability of estrogens?

<p>17a-ethinyl substituent (D)</p> Signup and view all the answers

What effect does the binding of anti-estrogens like tamoxifen have on estrogen receptor-alpha?

<p>Prevents the recruitment of co-activators to ER-alpha (B)</p> Signup and view all the answers

What is the mechanism of action of fulvestrant (ICI-182780) on estrogen receptor-alpha?

<p>Prevents binding of co-activators to ER-alpha (C)</p> Signup and view all the answers

What is the function of raloxifene in relation to estrogen receptor signaling?

<p>Partially transcriptionally active as an ER ligand (A)</p> Signup and view all the answers

Which of the following is a common use of drugs targeting the estrogen receptor?

<p>Treating osteoporosis (C)</p> Signup and view all the answers

Which type of ER modulator is used to treat breast cancer chemoprevention and chemotherapy?

<p>ER antagonists (B)</p> Signup and view all the answers

What is the most appropriate function of estrogen receptor alpha (ERa)?

<p>Transcription factor activation (C)</p> Signup and view all the answers

Where are the Zinc atoms contained in the estrogen receptor?

<p>In the DNA binding domain (B)</p> Signup and view all the answers

Which of the following tissues expresses both ERa and ERb?

<p>All of the above (D)</p> Signup and view all the answers

Which of the following best describes the estrogen receptor (ER) function?

<p>A ligand-activated transcription factor (A)</p> Signup and view all the answers

What is a common treatment for oral contraception that targets the estrogen receptor?

<p>ER agonists (A)</p> Signup and view all the answers

Which of the following is true about estrogen receptor signaling?

<p>It activates transcription factors to regulate gene expression (B)</p> Signup and view all the answers

What is the main difference between tamoxifen and fulvestrant in terms of ER binding?

<p>Fulvestrant competes for ER binding and induces ER degradation while tamoxifen only competes for ER binding (C)</p> Signup and view all the answers

Which function does fulvestrant not perform on the estrogen receptor?

<p>Inducing ER dimerization (A)</p> Signup and view all the answers

Which statement best describes the function of fulvestrant?

<p>Fulvestrant is a pure estrogen antagonist without agonist properties (C)</p> Signup and view all the answers

Which type of breast cancer is fulvestrant used to treat?

<p>Estrogen receptor-positive metastatic breast cancer (D)</p> Signup and view all the answers

Which of the following statements about fulvestrant is true?

<p>Fulvestrant bears a penta-fluorinated alkyl-substituent (D)</p> Signup and view all the answers

In which scenario would fulvestrant be used?

<p>When hormonal therapies such as tamoxifen have failed (D)</p> Signup and view all the answers

What is the impact of fulvestrant on estrogen signaling?

<p>Fulvestrant completely inhibits estrogen signaling (B)</p> Signup and view all the answers

Which of the following is a common use for fulvestrant?

<p>Treatment of estrogen receptor-positive metastatic breast cancer in postmenopausal women (D)</p> Signup and view all the answers

What is the function of 4-hydroxytamoxifen in breast tissue?

<p>It acts as an antagonist to inhibit transcription of estrogen-responsive genes. (D)</p> Signup and view all the answers

What gene variant may impact the effectiveness of tamoxifen in some patients?

<p>CYP2D6 (C)</p> Signup and view all the answers

What potential side effect has tamoxifen been linked to in some women?

<p>Endometrial cancer (B)</p> Signup and view all the answers

What is the role of CYP2D6 in tamoxifen metabolism?

<p>It converts tamoxifen into its more potent metabolites. (C)</p> Signup and view all the answers

What is the approved use of raloxifene in postmenopausal women?

<p>Treatment and prevention of osteoporosis (C)</p> Signup and view all the answers

What other use of raloxifene was approved by the FDA in 2007?

<p>As a chemopreventive medication against invasive breast cancer (A)</p> Signup and view all the answers

What is the effect of tamoxifen on bone tissue?

<p>It has anti-osteoporotic effects. (A)</p> Signup and view all the answers

What are poor metabolizers of tamoxifen characterized by?

<p>Lower levels of endoxifen and poorer clinical outcomes. (A)</p> Signup and view all the answers

Which of the following estrogenic agents can undergo enterohepatic recycling?

<p>1, 2, 3, 4 (D)</p> Signup and view all the answers

What is the route of administration for conjugated equine estrogens (CEE)?

<p>Oral, transdermal, or intravaginal (B)</p> Signup and view all the answers

What is the purpose of the estradiol transdermal system?

<p>To release estradiol through a rate-limiting membrane continuously upon application to intact skin (D)</p> Signup and view all the answers

What are the five estrogenic agents that target the estrogen receptor?

<p>Equilin sulfate, 17a-dihydroequilin, estrone sulfate, equilenin, estradiol (A)</p> Signup and view all the answers

What is the mechanism of action of the estradiol transdermal patch?

<p>The estradiol transdermal patch releases estradiol in a continuous manner (C)</p> Signup and view all the answers

What is the purpose of the enterohepatic recycling of E1-S?

<p>To increase the half-life of E1-S (A)</p> Signup and view all the answers

What is the purpose of hormonal replacement therapy (HRT) for the treatment of menopausal symptoms?

<p>To replace the hormones that are no longer produced by the body after menopause (D)</p> Signup and view all the answers

What is the advantage of using transdermal patches for systemic delivery of hormones?

<p>Transdermal patches bypass the first-pass metabolism in the liver (D)</p> Signup and view all the answers

Flashcards

Estrogen Receptor (ER)

A protein that binds to estrogen and acts as a transcription factor, regulating gene expression.

Estrogen Response Element (ERE)

A DNA sequence located in the promoter region of target genes, recognized by ER to activate transcription.

ERα (Estrogen Receptor alpha)

A subtype of ER that is primarily responsible for the classic estrogenic effects in reproductive tissues and other organs.

ERβ (Estrogen Receptor beta)

A subtype of ER involved in various physiological processes, including bone metabolism and brain function.

Signup and view all the flashcards

Estradiol (E2)

A natural hormone that binds to ERα and activates transcription, leading to various biological activities.

Signup and view all the flashcards

Anti-estrogens

A class of drugs that bind to ERα and block the action of estradiol, preventing estrogenic effects.

Signup and view all the flashcards

Tamoxifen

A medication known for its anti-estrogenic effects, commonly used to treat breast cancer.

Signup and view all the flashcards

Fulvestrant

A drug that directly binds to ERα and inhibits its activity, leading to degradation of the receptor.

Signup and view all the flashcards

4-OH-tamoxifen

A potent metabolite of tamoxifen, exhibiting stronger anti-estrogenic properties.

Signup and view all the flashcards

17α-ethinylestradiol (EE)

A synthetic, metabolically stable estrogen with prolonged activity.

Signup and view all the flashcards

Raloxifene

A medication with selective estrogen receptor modulation (SERM) properties, used to treat osteoporosis and breast cancer.

Signup and view all the flashcards

Diethylstilbestrol (DES)

A synthetic estrogen previously prescribed for menopausal symptoms but later withdrawn due to safety concerns.

Signup and view all the flashcards

Enterohepatic Recycling

A process where estrogens are reabsorbed back into the bloodstream after being metabolized in the gut.

Signup and view all the flashcards

Estrone Sulfate (E1-S)

A form of estrogen that undergoes enterohepatic recycling.

Signup and view all the flashcards

Conjugated Equine Estrogen (CEE)

A mixture of conjugated estrogenic compounds derived from pregnant mares' urine.

Signup and view all the flashcards

Hormonal Replacement Therapy (HRT)

A therapy that utilizes estrogen replacement to address menopausal symptoms.

Signup and view all the flashcards

Estrogen-only Therapy

A type of HRT where only estrogen is administered.

Signup and view all the flashcards

Estrogen/Progestin Combinations

A type of HRT where both estrogen and progestin are administered.

Signup and view all the flashcards

Transdermal Patches

A method of administering estrogen through the skin for systemic delivery.

Signup and view all the flashcards

Estradiol Transdermal system

A transdermal patch designed to release estradiol continuously for extended periods.

Signup and view all the flashcards

Steroid Hormone Receptors

A class of receptors that bind to steroid hormones, triggering a cascade of events that regulate gene expression.

Signup and view all the flashcards

ERα as a Ligand-Activated Transcription Factor

A ligand-activated nuclear transcription factor that binds to estrogen and regulates gene expression.

Signup and view all the flashcards

Estradiol Activates ERα

The binding of estradiol to ERα leads to a conformational change that activates transcription.

Signup and view all the flashcards

Tamoxifen Inhibits ERα

Tamoxifen binds to ERα but does not activate transcription, rather inhibiting its activity.

Signup and view all the flashcards

Fulvestrant Inhibits and Degrades ERα

Fulvestrant binds to ERα, blocking the binding of estradiol and leading to the degradation of the receptor.

Signup and view all the flashcards

Metabolism of Tamoxifen

CYP2D6 enzyme metabolizes tamoxifen to its more potent metabolite, 4-OH-tamoxifen.

Signup and view all the flashcards

Tamoxifen as SERM

Tamoxifen is a Selective Estrogen Receptor Modulator (SERM), acting as an antagonist in breast tissue and agonist in bone.

Signup and view all the flashcards

Study Notes

Estrogen Receptor Signaling

  • Estrogen Receptor (ER) is a ligand-activated transcription factor.
  • Estrogen Response Element (ERE) is present in the promoter region of target genes.
  • ERα (Estrogen Receptor alpha) and ERβ (Estrogen Receptor beta) are two subtypes of ER.

ERα Ligand Binding

  • Estradiol (E2) is a natural ligand that binds to ERα, causing a conformational change that activates transcription.
  • Tamoxifen and fulvestrant are anti-estrogens that bind to ERα, causing a conformational change that prevents the recruitment of co-activators.
  • 4-OH-tamoxifen is an active metabolite of tamoxifen.

Estrogen Receptor Ligands

  • Estradiol (E2) is a potent ER ligand.
  • 17α-ethinylestradiol (EE) is a metabolically stable ER ligand.
  • Raloxifene is a selective ER modulator (SERM) that targets osteoporosis and breast carcinogenesis.
  • Diethylstilbestrol (DES) is a synthetic ER ligand.

Targeting ERα

  • Estradiol and tamoxifen have different effects on ERα, with estradiol causing a transcriptionally active conformation and tamoxifen causing a transcriptionally inactive conformation.
  • Fulvestrant is a pure ER antagonist that binds to ERα, competing with estradiol, and also induces ERα degradation.

Steroid Hormone Receptors

  • The classic model of steroid hormone receptors involves ligand binding, causing a conformational change that activates transcription.
  • ERα is a ligand-activated nuclear transcription factor.

Exam Questions

  • Fulvestrant is a potent anti-estrogen that binds to ERα, competing with estradiol, and induces ERα degradation.
  • Tamoxifen is metabolized by CYP2D6 to 4-OH-tamoxifen, which is a more potent metabolite.

Enterohepatic Recycling

  • Enterohepatic recycling of estrogens occurs through intestinal microbial deconjugation and reuptake of free estrogens.
  • Estrone sulfate (E1-S) and conjugated equine estrogen (CEE) undergo enterohepatic recycling.

Hormonal Replacement Therapy

  • Hormonal replacement therapy is used to treat menopausal symptoms.
  • Estrogen-only therapy involves the use of estradiol acetate, conjugated equine estrogens (CEE), or micronized 17β-estradiol.
  • Estrogen/progestin combinations involve the use of CEE + medroxyprogesterone acetate (MPA) or ethynylestradiol (EE) + norethindrone.

Transdermal Patches

  • Transdermal patches are used for systemic delivery of estrogen and other cardiovascular agents, analgesics, and hormones.
  • Estradiol transdermal system is designed to release estradiol continuously upon application to intact skin.

Studying That Suits You

Use AI to generate personalized quizzes and flashcards to suit your learning preferences.

Quiz Team

Related Documents

PCOL 826B Steroid Lecture 2 (2022) PDF

Description

Explore drugs targeting the estrogen receptor, including their use in oral contraception, breast cancer chemoprevention, chemotherapy, infertility treatment, hormone replacement therapy [HRT], and osteoporosis. Learn about SERM [selective ER modulators], ER agonists, and ER antagonists. Study the medicinal chemistry of Estrogen Receptor alpha.

More Like This

Use Quizgecko on...
Browser
Open
Browser
Browser