Determination of the Effects of Baclofen on 5- Alpha Reductase and Aromatase Gene Expressions in Polycystic Ovary Syndrome

Tohidi, Fateme (2019) Determination of the Effects of Baclofen on 5- Alpha Reductase and Aromatase Gene Expressions in Polycystic Ovary Syndrome. Masters thesis, Faculty of Sciences.

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Abstract

Research Aim: Gamma-amino-butyric acid (GABA) is one of the most important inhibitory neurotransmitters in regulation of hypothalamus- pituitary- gonad axis activity. Aromatase and 5-alpha reductase enzymes are involved in the conversion of testosterone to estradiol or dihydrotestosterone respectively. Polycystic ovary syndrome (PCOS) is accompanied by the changes in the gene expression levels of steroidogenesis enzymes and the secretion of sexual hormones. In the present study, the effects of baclofen was investigated on the relative expression of aromatase and 5-alpha reductase genes in normal and PCOS rats. Research method: Twenty female Wistar rats weighing 180-200 g were divided into four groups (n=5 in each group). Fifteen rats received 2mg estradiol valerate in 0.5 ml sesame oil intramuscularly in order to induce PCOS. PCOS rats received intraperitoneal injection of saline or 5 or 10 mg/Kg BW baclofen for 14 days. Five intact rats as the control group received intraperitoneal injection of saline for 14 days in the estrus phase. One day after the last injection, the hypothalamic specimens were isolated and the mean relative gene expression of aromatase and 5-alpha reductase was measured by RT-PCR. Data were analyzed by unpaired T-test, one-way ANOVA and Tukey post hoc test in SPSS software. Results were reported with a significant level of P≤0.05. Findings: The mean relative expression of aromatase gene was significantly decreased in PCOS group compared to intact rats. Mean relative expression of 5-alpha reductase gene was significantly increased in PCOS group compared to intact control group. Different doses of baclofen did not cause a significant increase in the mean relative gene expression of aromatase in comparison to PCOS rats. Mean relative gene expression of 5-alpha reductase significantly increased in PCOS rat receiving 10mg/Kg baclofen compared to PCOS control group. Conclusion: GABAergic signaling pathway may be involved in the controlling of sexual hormones secretion in PCOS patients partly via down or up- regulation of steroidogenesis enzymes synthesis.

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