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{{WBRQuestion
{{WBRQuestion
|QuestionAuthor={{Rim}}
|QuestionAuthor= {{YD}} (Reviewed by  {{YD}} and  {{AJL}})
|ExamType=USMLE Step 1
|ExamType=USMLE Step 1
|Prompt=Androstenedione is an androgen formed by theca cells and transported to granulosa cells. It is converted to estrogen by the action of enzyme X under the positive hormonal effect of follicle-stimulating hormone (FSH). FSH has time and dose-dependent activity on enzyme X. The illustration shown below demonstrates the enzymatic conversion of androstenedione to estrogen. Pharmacologic inhibition of enzyme X is most likely prescribed in which pathological condition?
|MainCategory=Pharmacology
|SubCategory=Oncology
|MainCategory=Pharmacology
|SubCategory=Oncology
|MainCategory=Pharmacology
|SubCategory=Oncology
|MainCategory=Pharmacology
|MainCategory=Pharmacology
|MainCategory=Pharmacology
|SubCategory=Oncology
|MainCategory=Pharmacology
|SubCategory=Oncology
|MainCategory=Pharmacology
|SubCategory=Oncology
|MainCategory=Pharmacology
|SubCategory=Oncology
|MainCategory=Pharmacology
|MainCategory=Pharmacology
|SubCategory=Oncology
|Prompt=Androstenedione, an androgen formed by theca cells and transported to granulosa cells, is converted to estrogen by the action of enzyme X under the positive hormonal effect of follicle-stimulating hormone (FSH). On enzyme X, FSH's activity is demonstrated to be time- and dose-dependent. The illustration below demonstrates the enzymatic conversion of androstenedione to estrogen. Pharmacological inhibition of enzyme X is most likely prescribed in which of the following conditions?


[[Image:WBR0339.png|500px]]
[[Image:WBR0339.png|650px]]
|Explanation=Enzyme X described above is aromatase. FSH has a time- and dose-dependent mechanism for activation of aromatase. The enzyme is responsible for the conversion of androstenedione in granulosa cell to estrogen. Inhibition of aromatase by pharmacologic therapy (aromatase inhibitors), such as anastrozole and exemestane, is particularly beneficial in post-menopausal women with breast cancer. In these patients, inhibition of peripheral estrogen production is key for targeted therapy.
|Explanation=The enzyme described above is [[aromatase]]. [[FSH]] has a time- and dose-dependent mechanism for the activation of [[aromatase]]. In granulosa cells, [[aromatase]] is responsible for the conversion of androstenedione to estrogen. Inhibition of [[aromatase]] by pharmacological therapy ([[aromatase]] inhibitors), such as anastrozole and exemestane, is particularly beneficial for post-menopausal women with breast cancer. In these patients, inhibition of peripheral estrogen production is essential for targeted therapy.
 
Educational Objective:
Aromatase is an enzyme stimulated by FSH and is responsible for the conversion of androstenedione to estrogen. Aromatase inhibitors, such as anastrozole and exemestane are clinically useful in post-menopausal women with breast cancer.
|AnswerA=Benign prostate hyperplasia (BPH)
|AnswerA=Benign prostate hyperplasia (BPH)
|AnswerAExp=Patients with BPH are prescribed alpha-1-antagonists, such as tamsulosin, or 5-alpha-reductase inhibitors, such as finasteride
|AnswerAExp=Patients with BPH are often prescribed alpha-1-antagonists, such as tamsulosin, or 5-alpha-reductase inhibitors, such as finasteride.
|AnswerB=Prostate adenocarcinoma
|AnswerB=Prostate adenocarcinoma
|AnswerBExp=Anti-androgens such as flutamide are prescribed in prostate adenocarcinoma.
|AnswerBExp=Anti-androgens, such as flutamide, are typically prescribed to patients with prostate adenocarcinoma.
|AnswerC=Breast cancer in post-menopausal women
|AnswerC=Breast cancer among post-menopausal women
|AnswerCExp=Aromatase inhibitors are prescribed for breast cancer in post-menopausal women to decrease the peripheral production of estrogen.
|AnswerCExp=[[Aromatase]] inhibitors are often prescribed to post-menopausal women with breast cancer in order to decrease the peripheral production of estrogen.
|AnswerD=Contraception
|AnswerD=Contraception
|AnswerDExp=Hormone replacement therapy, such as progestin and estrogen, may be used for contraception.
|AnswerDExp=Hormone replacement therapy, such as progestin and estrogen, may be used for contraception.
|AnswerE=Triple negative breast cancer
|AnswerE=Triple negative breast cancer
|AnswerEExp=Patients with triple negative breast cancer, defined as breast cancers that do not express estrogen receptors (ER), progesterone receptors (PR), or Her2/neu, do not benefit from hormonal therapy, such as selective estrogen receptor modulators (SERMs) or aromatase inhibitors. Triple negative breast cancers are difficult to treat due to absence of specific targets for therapy.
|AnswerEExp=Patients with triple negative breast cancer, defined as breast cancers that do not express estrogen receptors (ER), progesterone receptors (PR), and Her2/neu, do not benefit from hormonal therapy, such as selective estrogen receptor modulators (SERMs) or [[aromatase]] inhibitors.
|EducationalObjectives=[[Aromatase]], an enzyme stimulated by FSH, is responsible for the conversion of androstenedione to estrogen. [[Aromatase]] inhibitors, such as anastrozole and exemestane, are clinically beneficial among post-menopausal women with breast cancer.
|References=First Aid 2014 page 590
|RightAnswer=C
|RightAnswer=C
|WBRKeyword=aromatase, inhibitor, inhibition, anastrozole, exemestane, postmenopausal, post-menopausal, post, menopausal, menopause, breast, cancer, estrogen, androstenedione, receptor, granulosa, cell, peripheral, conversion, FSH, follicle, stimulating, hormone
|WBRKeyword=Aromatase, Aromatase inhibitor, Anastrozole, Enzyme, Enzyme X, Exemestane, Postmenopausal women, Menopause, Breast cancer, Estrogen, Androstenedione, Receptor, Granulosa cell, FSH, Hormone
|Approved=No
|Approved=Yes
}}
}}

Latest revision as of 00:14, 28 October 2020
Author [[PageAuthor::Yazan Daaboul, M.D. (Reviewed by Yazan Daaboul, M.D. and Alison Leibowitz [1])]]
Exam Type ExamType::USMLE Step 1
Main Category MainCategory::Pharmacology
Sub Category SubCategory::Oncology
Prompt [[Prompt::Androstenedione, an androgen formed by theca cells and transported to granulosa cells, is converted to estrogen by the action of enzyme X under the positive hormonal effect of follicle-stimulating hormone (FSH). On enzyme X, FSH's activity is demonstrated to be time- and dose-dependent. The illustration below demonstrates the enzymatic conversion of androstenedione to estrogen. Pharmacological inhibition of enzyme X is most likely prescribed in which of the following conditions?

]]

Answer A AnswerA::Benign prostate hyperplasia (BPH)
Answer A Explanation AnswerAExp::Patients with BPH are often prescribed alpha-1-antagonists, such as tamsulosin, or 5-alpha-reductase inhibitors, such as finasteride.
Answer B AnswerB::Prostate adenocarcinoma
Answer B Explanation AnswerBExp::Anti-androgens, such as flutamide, are typically prescribed to patients with prostate adenocarcinoma.
Answer C AnswerC::Breast cancer among post-menopausal women
Answer C Explanation [[AnswerCExp::Aromatase inhibitors are often prescribed to post-menopausal women with breast cancer in order to decrease the peripheral production of estrogen.]]
Answer D AnswerD::Contraception
Answer D Explanation AnswerDExp::Hormone replacement therapy, such as progestin and estrogen, may be used for contraception.
Answer E AnswerE::Triple negative breast cancer
Answer E Explanation [[AnswerEExp::Patients with triple negative breast cancer, defined as breast cancers that do not express estrogen receptors (ER), progesterone receptors (PR), and Her2/neu, do not benefit from hormonal therapy, such as selective estrogen receptor modulators (SERMs) or aromatase inhibitors.]]
Right Answer RightAnswer::C
Explanation [[Explanation::The enzyme described above is aromatase. FSH has a time- and dose-dependent mechanism for the activation of aromatase. In granulosa cells, aromatase is responsible for the conversion of androstenedione to estrogen. Inhibition of aromatase by pharmacological therapy (aromatase inhibitors), such as anastrozole and exemestane, is particularly beneficial for post-menopausal women with breast cancer. In these patients, inhibition of peripheral estrogen production is essential for targeted therapy.

Educational Objective: Aromatase, an enzyme stimulated by FSH, is responsible for the conversion of androstenedione to estrogen. Aromatase inhibitors, such as anastrozole and exemestane, are clinically beneficial among post-menopausal women with breast cancer.
References: First Aid 2014 page 590]]

Approved Approved::Yes
Keyword WBRKeyword::Aromatase, WBRKeyword::Aromatase inhibitor, WBRKeyword::Anastrozole, WBRKeyword::Enzyme, WBRKeyword::Enzyme X, WBRKeyword::Exemestane, WBRKeyword::Postmenopausal women, WBRKeyword::Menopause, WBRKeyword::Breast cancer, WBRKeyword::Estrogen, WBRKeyword::Androstenedione, WBRKeyword::Receptor, WBRKeyword::Granulosa cell, WBRKeyword::FSH, WBRKeyword::Hormone
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