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{{WBRQuestion
{{WBRQuestion
|QuestionAuthor=[[User:Gonzalo Romero|Gonzalo A. Romero, M.D.]] [mailto:gromero@wikidoc.org]
|QuestionAuthor=[[User:Gonzalo Romero|Gonzalo A. Romero, M.D.]] [mailto:gromero@wikidoc.org] (Reviewed by Will Gibson)
|ExamType=USMLE Step 1
|ExamType=USMLE Step 1
|MainCategory=Pharmacology, Physiology
|MainCategory=Pharmacology, Physiology
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|MainCategory=Pharmacology, Physiology
|MainCategory=Pharmacology, Physiology
|SubCategory=Endocrine, Reproductive
|SubCategory=Endocrine, Reproductive
|MainCategory=Pharmacology, Physiology
|MainCategory=Pharmacology, Physiology
|MainCategory=Pharmacology, Physiology
|MainCategory=Pharmacology, Physiology
|MainCategory=Pharmacology, Physiology
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|MainCategory=Pharmacology, Physiology
|MainCategory=Pharmacology, Physiology
|SubCategory=Endocrine, Reproductive
|SubCategory=Endocrine, Reproductive
|Prompt=A pharmacist is eager to study different models in reproductive pharmacology.  He is very passionate about translational research. He is planning a study with mice in order to determine the effects of a novel drug called “Pharma-WBR”. He knows that the drug is supposed to work in the hypothalamus, to regulate the release of different pituitary hormones.  He measures serum concentration and determines that the drug causes different changes in FSH and LH if used continuously or pulsatile. He finds analogy of a drug existing in the market.  Which of the following drugs has a similar mechanism of action as “Pharma-WBR”?
|Prompt=A pharmacist is planning a study with mice in order to determine the effects of a novel drug called “Compound A572”. He knows that the drug is supposed to work in the hypothalamus, to regulate the release of different pituitary hormones.  He measures serum concentration of hypothalamic hormones and determines that the drug causes different changes in FSH and LH if dosed continuously or in a pulsatile fashion. Which of the following drugs has a similar mechanism of action as “Compound A572”?
|Explanation=Leuprolide is a [[GnRH ]] analog. If used in pulsatile fashion, it acts as an agonist. If used continuously, it acts as an antagonist, because it downregulates the GnRH receptor in pituitary, therefore decreasing FSH and LH. It is used continuously with flutamide to treat prostatic cancer or uterine fibroids.  It is used pulsatile in cases of infertility.
|Explanation=[[File:Pituitary Phys.png|center|600px]]
<font color="MediumBlue"><font size="4">'''Educational Objective:''' </font></font>
 
# Leuprolide is a GrRH analog, which acts on the pituitary.
[[Leuprolide]] is a [[GnRH ]] analogue. GnRH is normally secreted in a pulsatile fashion to stimulate the HPA axis. GnRH secretion is negatively regulated by prolactin secreted in the pituitary. GnRH is thought to be positively regulated by kisspeptin, but the precise circuitry underlying the GnRH pulse generator is still unclear. Leuprolide acts similarly to endogenous GnRH; when used in pulsatile fashion, it acts as an agonist, while if used continuously, it acts as an antagonist. Continuous dosing of the drug causes the pituitary to downregulate GnRH receptors due to negative feedback. The anterior pituitary thereby decreases the production of Follice Stimulating Hormone (FSH) and Leutenizing Hormone (LH). Recall that FSH and LH are responsible for stimulating the release of sex hormones in both men and women. Leuprolide therefore causes hypogonadism and has important therapeutic roles in diseases associated with the activity of sex hormones.
# If used continously it decreases FSH and LH.  If used in a pulsatile fashion it increases FSH and LH levels.
 
[[File:Pituitary Phys.png|center|400px]]<br>
Leuprolide is often used continuously with flutamide to treat prostatic cancer or uterine fibroids.  [[Leuprolide]] is administered in pulsatile dosing in cases of infertility.
'''References:'''
First Aid 2012 for Step 1, Reproductive-Pharmacology chapter.
|AnswerA=Flutamide
|AnswerA=Flutamide
|AnswerAExp=<font color="red">'''Incorrect.'''</font> [[Flutamide]] is a nonsteroidal competitive inhibitor of androgens at the testosterone receptor used in
|AnswerAExp=[[Flutamide]] is a nonsteroidal competitive inhibitor of androgens at the androgen receptor. It is used to treat [[prostate cancer]] and hyperandrogenism in polycystic ovarian syndrome.
prostate cancer.
|AnswerB=Finasteride
|AnswerB=Finasteride
|AnswerBExp=<font color="red">'''Incorrect.'''</font> [[Finasteride]] is a 5 alfa-reductase inhibitor used to treat BPH and male-pattern baldness.
|AnswerBExp=[[Finasteride]] is a 5 alpha-reductase inhibitor used to treat benign prostatic hyperplasia and male-pattern baldness.
|AnswerC=Mifepristone
|AnswerC=Mifepristone
|AnswerCExp=<font color="red">'''Incorrect.'''</font> [[Mifepristone]] is a competitive inhibitor of progestins at the progesterone receptors. It is used to terminate pregnancy in combination with [[misoprostol]] (PGE1 analog).
|AnswerCExp=[[Mifepristone]] is a competitive inhibitor of progestins at the [[progesterone]] receptors. It is used to terminate [[pregnancy]] in combination with [[misoprostol]] (PGE1 analogue).
|AnswerD=Ketoconazol
|AnswerD=Ketoconazole
|AnswerDExp=<font color="red">'''Incorrect.'''</font>
|AnswerDExp=[[Ketoconazole]] is a steroid synthesis inhibitor that inhibits desmolase, the enzyme responsible for transforming [[cholesterol]] into [[pregnenolone]].
|AnswerE=Leuprolide
|AnswerE=Leuprolide
|AnswerEExp=<font color="Green">'''Correct.'''</font> See overall explanation.
|AnswerEExp=Leuprolide is a GnRH analogue. When dosed continuously, it inhibits the production of FSH and LH, thereby leading to hypogonadism. When dosed in a pulsatile manner, it increases the production of FSH and LH. In turn, FSH and LH stimulate the production of sex hormones.
|EducationalObjectives=Leuprolide is a GnRH analogue, which acts on the pituitary. If used continously it decreases FSH and LH.  If used in a pulsatile fashion it increases FSH and LH levels.
|References=Okamura H, Tsukamura H, Ohkura S, Uenoyama Y, Wakabayashi Y, Maeda K. Kisspeptin and GnRH pulse generation. Adv Exp Med Biol. 2013;784:297-323.
<br>Friedman, A. J., Barbieri, R. L., Doubilet, P. M., Fine, C. A. L. L. I. O. P. E., & Schiff, I. S. A. A. C. (1988). A randomized, double-blind trial of a gonadotropin releasing-hormone agonist (leuprolide) with or without medroxyprogesterone acetate in the treatment of leiomyomata uteri. Fertility and sterility, 49(3), 404-409.
<br>Crawford, E. D., Eisenberger, M. A., McLeod, D. G., Spaulding, J. T., Benson, R., Dorr, F. A., ... & Goodman, P. J. (1989). A controlled trial of leuprolide with and without flutamide in prostatic carcinoma. New England Journal of Medicine, 321(7), 419-424.
<br>First Aid 2014 page 590
|RightAnswer=E
|RightAnswer=E
|WBRKeyword=Pituitary hormones
|WBRKeyword=Pituitary hormones, Pituitary, Hypothalamus, GnRH, Gonadotropins, Gonadotropin releasing hormone, Gonadotropin, Leuprolide, Hormone
|Approved=No
|Approved=Yes
}}
}}

Latest revision as of 00:48, 28 October 2020

 
Author [[PageAuthor::Gonzalo A. Romero, M.D. [1] (Reviewed by Will Gibson)]]
Exam Type ExamType::USMLE Step 1
Main Category MainCategory::Pharmacology, MainCategory::Physiology
Sub Category SubCategory::Endocrine, SubCategory::Reproductive
Prompt [[Prompt::A pharmacist is planning a study with mice in order to determine the effects of a novel drug called “Compound A572”. He knows that the drug is supposed to work in the hypothalamus, to regulate the release of different pituitary hormones. He measures serum concentration of hypothalamic hormones and determines that the drug causes different changes in FSH and LH if dosed continuously or in a pulsatile fashion. Which of the following drugs has a similar mechanism of action as “Compound A572”?]]
Answer A AnswerA::Flutamide
Answer A Explanation [[AnswerAExp::Flutamide is a nonsteroidal competitive inhibitor of androgens at the androgen receptor. It is used to treat prostate cancer and hyperandrogenism in polycystic ovarian syndrome.]]
Answer B AnswerB::Finasteride
Answer B Explanation [[AnswerBExp::Finasteride is a 5 alpha-reductase inhibitor used to treat benign prostatic hyperplasia and male-pattern baldness.]]
Answer C AnswerC::Mifepristone
Answer C Explanation [[AnswerCExp::Mifepristone is a competitive inhibitor of progestins at the progesterone receptors. It is used to terminate pregnancy in combination with misoprostol (PGE1 analogue).]]
Answer D AnswerD::Ketoconazole
Answer D Explanation [[AnswerDExp::Ketoconazole is a steroid synthesis inhibitor that inhibits desmolase, the enzyme responsible for transforming cholesterol into pregnenolone.]]
Answer E AnswerE::Leuprolide
Answer E Explanation [[AnswerEExp::Leuprolide is a GnRH analogue. When dosed continuously, it inhibits the production of FSH and LH, thereby leading to hypogonadism. When dosed in a pulsatile manner, it increases the production of FSH and LH. In turn, FSH and LH stimulate the production of sex hormones.]]
Right Answer RightAnswer::E
Explanation [[Explanation::

Leuprolide is a GnRH analogue. GnRH is normally secreted in a pulsatile fashion to stimulate the HPA axis. GnRH secretion is negatively regulated by prolactin secreted in the pituitary. GnRH is thought to be positively regulated by kisspeptin, but the precise circuitry underlying the GnRH pulse generator is still unclear. Leuprolide acts similarly to endogenous GnRH; when used in pulsatile fashion, it acts as an agonist, while if used continuously, it acts as an antagonist. Continuous dosing of the drug causes the pituitary to downregulate GnRH receptors due to negative feedback. The anterior pituitary thereby decreases the production of Follice Stimulating Hormone (FSH) and Leutenizing Hormone (LH). Recall that FSH and LH are responsible for stimulating the release of sex hormones in both men and women. Leuprolide therefore causes hypogonadism and has important therapeutic roles in diseases associated with the activity of sex hormones.

Leuprolide is often used continuously with flutamide to treat prostatic cancer or uterine fibroids. Leuprolide is administered in pulsatile dosing in cases of infertility.
Educational Objective: Leuprolide is a GnRH analogue, which acts on the pituitary. If used continously it decreases FSH and LH. If used in a pulsatile fashion it increases FSH and LH levels.
References: Okamura H, Tsukamura H, Ohkura S, Uenoyama Y, Wakabayashi Y, Maeda K. Kisspeptin and GnRH pulse generation. Adv Exp Med Biol. 2013;784:297-323.
Friedman, A. J., Barbieri, R. L., Doubilet, P. M., Fine, C. A. L. L. I. O. P. E., & Schiff, I. S. A. A. C. (1988). A randomized, double-blind trial of a gonadotropin releasing-hormone agonist (leuprolide) with or without medroxyprogesterone acetate in the treatment of leiomyomata uteri. Fertility and sterility, 49(3), 404-409.
Crawford, E. D., Eisenberger, M. A., McLeod, D. G., Spaulding, J. T., Benson, R., Dorr, F. A., ... & Goodman, P. J. (1989). A controlled trial of leuprolide with and without flutamide in prostatic carcinoma. New England Journal of Medicine, 321(7), 419-424.
First Aid 2014 page 590]]

Approved Approved::Yes
Keyword WBRKeyword::Pituitary hormones, WBRKeyword::Pituitary, WBRKeyword::Hypothalamus, WBRKeyword::GnRH, WBRKeyword::Gonadotropins, WBRKeyword::Gonadotropin releasing hormone, WBRKeyword::Gonadotropin, WBRKeyword::Leuprolide, WBRKeyword::Hormone
Linked Question Linked::
Order in Linked Questions LinkedOrder::