Document Detail

Direct protection by a gonadotropin-releasing hormone analog from doxorubicin-induced granulosa cell damage.
MedLine Citation:
PMID:  17028438     Owner:  NLM     Status:  MEDLINE    
BACKGROUND/AIMS: Recent clinical applications suggest a beneficial effect of gonadotropin-releasing hormone analog (GnRHa) as a gonadal protector from chemotherapy-induced premature ovarian failure. This study aimed to determine cellular mechanisms involved in the protective action of GnRHa against granulosa cell damage caused by doxorubicin. METHODS: Granulosa cells were obtained by ultrasound-guided follicular aspiration from patients undergoing in vitro fertilization, and screened for GnRH receptor expression prior to analyses. The cellular function was assessed by measuring the conversion of exogenously supplied androstenedione to estradiol-beta (E2) in response to follicle-stimulating hormone (FSH) (1 microM). RESULTS: Exposing to doxorubicin for 12 h before FSH stimulation caused a concentration-dependent inhibition of the E2 secretion to a minimum level of 20% of control. When the cells were incubated with a GnRHa for 12 h before and during exposure to doxorubicin, granulosa cells produced an equal level of E2 to that of control cells. The protective action of GnRHa was dose-dependent; a half-maximal effect occurred at 10 nM. Preincubation with GnRHa alone had no effect on FSH-induced E2 production. CONCLUSION: These findings demonstrate that a GnRHa may retard doxorubicin-induced granulosa cell damage, suggesting an additional GnRH activity to protect the gonads during chemotherapy through GnRH receptor-mediated mechanism(s).
Atsushi Imai; Michiyo Sugiyama; Tatsuro Furui; Teruhiko Tamaya; Tsukasa Ohno
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Publication Detail:
Type:  Journal Article     Date:  2006-10-04
Journal Detail:
Title:  Gynecologic and obstetric investigation     Volume:  63     ISSN:  0378-7346     ISO Abbreviation:  Gynecol. Obstet. Invest.     Publication Date:  2007  
Date Detail:
Created Date:  2007-02-14     Completed Date:  2007-03-29     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7900587     Medline TA:  Gynecol Obstet Invest     Country:  Switzerland    
Other Details:
Languages:  eng     Pagination:  102-6     Citation Subset:  IM    
Department of Obstetrics and Gynecology, Gifu University School of Medicine, Gifu, Japan.
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MeSH Terms
Androstenedione / metabolism
Antibiotics, Antineoplastic / adverse effects*
Buserelin / pharmacology*,  therapeutic use
Dose-Response Relationship, Drug
Doxorubicin / adverse effects*
Estradiol / metabolism*
Follicle Stimulating Hormone / pharmacology
Gonadotropin-Releasing Hormone / agonists*
Granulosa Cells / drug effects*,  metabolism
Leuprolide / pharmacology*,  therapeutic use
Reg. No./Substance:
0/Antibiotics, Antineoplastic; 23214-92-8/Doxorubicin; 33515-09-2/Gonadotropin-Releasing Hormone; 50-28-2/Estradiol; 53714-56-0/Leuprolide; 57982-77-1/Buserelin; 63-05-8/Androstenedione; 9002-68-0/Follicle Stimulating Hormone

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