Long-term effects of GnRH agonist, GnRH antagonist, and estrogen plus progesterone treatment on apoptosis related genes in rat ovary

Objective To define the long-term effects of GnRH antagonist, GnRH agonist, and estrogen plus progesterone treatments on apoptosis and apoptosis-related gene expressions, including bcl2, bax, and cyt c in rat ovary. Design Prospective placebo-controlled experimental study. Setting Obstetrics and Gynecology and Medical Biology and Genetics university departments. Animal(s) Forty female wistar rats that were 3 to 4 mounths of age. Intervention(s) Forty rats were randomly divided into 4 groups of 10 each. In group 1 (control) each rat received normal saline as placebo by gastric lavage. In group 2 (GnRH agonist) 1 mg/kg leuprolide acetate in depot form was given for 30 days. In group 3 (GnRH antagonist) each animal received 0.1 mg/kg cetrorelix every 2 days. In group 4 (estrogen plus progesterone) 0.5 mg/kg estradiol valerate and norethisteron enantate in depot form was given every 30 days. After 60 days, the animals were killed. Main Outcome Measure(s) Assessment of morphology, histology of ovaries, determination of the number of apoptotic cells, and analysis of apoptosis-related gene expression of bcl2, bax, and cyt c in the rat ovaries. Result(s) Long-term GnRH antagonist treatment significantly increased bax gene expression, but the ratio of bcl2:bax gene expression was constant compared with control group. The GnRH agonist treatment significantly increased cyt c gene expression, and estrogen plus progesteron treatment significantly decreased bcl 2 and significantly increased cyt c expressions. In the estrogen plus progesterone group, ovaries were cystic and larger than in the other groups. There was no significant morphologic change between the other groups. Conclusion(s) Long-term administration of GnRH agonist, GnRH antagonist, and estrogen plus progesterone can modulate the apoptosis-related genes in rat ovary. Although GnRH antagonist treatment does not influence apoptosis, GnRH angonist and estrogen plus progesterone treatments seem to influence apoptosis in rat the ovary. Further clinical studies focusing on the effect of these agents on apoptosis-related genes could be performed.