[Effect of GnRH analogs on the expression of Bcl-2 gene family in the ovary of rats with cyclophosphamide-induced ovarian damage].
OBJECTIVE
To study the effect of gonadotroph-releasing hormone (GnRH) agonist (GnRH-a) and GnRH antagonist (GnRH-ant) against cyclophosphamide (CTX)-induced gonadotoxicity in female rats.


METHODS
Thirty-six female SD rats were divided randomly into 6 groups to receive treatment with normal saline (NS), CTX, GnRH-a+NS, GnRH-a+CTX, GnRH-ant+NS, GnRH-ant+CTX, respectively. The rats were sacrificed between the first and second week after termination of the medication to compare the weight of the ovaries, the number of the primordial follicles and the follicle growth. The expressions of bcl-2 and bax mRNA in the ovaries were examined using RT-PCR.


RESULTS
The number of the primordial follicles was significantly greater and that of the growing follicles significantly lower in GnRH-a+NS and GnRH-a+CTX groups than in the GnRH-ant+CTX and CTX groups (P<0.05). The rats in GnRH-a+NS and GnRH-a+CTX groups had the lowest ovarian weight among 6 the groups (P<0.05). The bcl-2 mRNA level in the GnRH-ant+NS group was significantly higher than that in the other groups (P<0.05). The Bax mRNA in the GnRH-a+NS and GnRH-a+CTX groups was significantly higher than that in the NS group (P<0.05), but close to that in the CTX group (P>0.05); bax mRNA expression in the GnRH-ant+NS group was significantly lower than that in the NS group (P<0.05), but in GnRH-ant+CTX group, its expression was close to that in the NS group (P>0.05).


CONCLUSIONS
In female rats exposed to CTX, the GnRH analogs provides ovarian protection against CTX-induced gonadotoxicity by regulating the expression of the Bax mRNA in the ovary. GnRH-a may decrease the sensitivity of the follicles to CTX-induced gonadotoxicity by promoting follicle apoptosis and inhibiting follicle proliferation, and GnRH-ant increases the sensitivity to the CTX through a reverse effect on the follicles.
Peng
Ping
P
Department of Obstetrics and Gynecology, Guangzhou General Hospital of Guangzhou Command, Guangzhou 510010, China. pengping1967@yahoo.com.cn
Yang
Dong-Zi
DZ
Yang
Chuan-Hong
CH
Zhang
Wei
W
Zhang
Yan-Ling
YL
Liu
Jia
J
Ye
Chang-Lan
CL
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D003520:Cyclophosphamide / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists* / Q000037:antagonists & inhibitors*; D010053:Ovary / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism*
C494828:Bax protein, rat; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D051028:bcl-2-Associated X Protein; D007987:Gonadotropin-Releasing Hormone; D003520:Cyclophosphamide