DefinePK

Research Objective

To study the effect of RANKL inhibitor on serum FSH, LH, and testosterone levels in a letrozole-induced rat model of PCOS.

Methodology

Experimental animal study involving thirty adult female Wistar Albino rats (6-8 weeks old, 120-150 gm). Rats were divided into three groups: Control (Group A), Letrozole-induced PCOS (Group B), and RANKL inhibitor (Denosumab) treated (Group C). PCOS was induced in Groups B and C by oral administration of letrozole (1 mg/kg) for 21 days. Group C received Denosumab (0.25 mg/kg subcutaneously) for 4 weeks after PCOS induction. Blood samples were collected via cardiac puncture at the end of the experiment and analyzed using ELISA for serum LH, FSH, and testosterone levels. Statistical analysis was performed using SPSS 21.0 with one-way ANOVA and Tukey's post hoc test.

Methodology Flowchart

                        graph TD
    A["Recruit 30 Adult Female Wistar Albino Rats"] --> B["Divide into 3 Groups: Control, PCOS, RANKL Inhibitor"];
    B --> C["Induce PCOS with Letrozole"1 mg/kg/day for 21 days" in Groups B & C"];
    C --> D["Administer Denosumab"0.25 mg/kg SC for 4 weeks" to Group C"];
    D --> E["Collect Blood Samples via Cardiac Puncture"];
    E --> F["Analyze Serum LH, FSH, Testosterone via ELISA"];
    F --> G["Statistical Analysis: SPSS 21.0, ANOVA, Tukey's Test"];
    G --> H["Interpret Results and Draw Conclusions"];                    

Discussion

The study suggests that RANKL inhibitors, specifically Denosumab, may help ameliorate hormonal imbalances and associated weight gain in a letrozole-induced rat model of PCOS. The observed decrease in LH and testosterone, and increase in FSH with Denosumab treatment, indicate a potential therapeutic role in restoring hormonal equilibrium. The reduction in body and ovarian weight gain with Denosumab treatment also suggests a beneficial effect.

Key Findings

- Letrozole-induced PCOS group showed significantly higher LH and testosterone levels and significantly lower FSH levels compared to the control group.
- Denosumab treatment significantly decreased LH and testosterone levels compared to the PCOS group, but these remained higher than the control group.
- Denosumab treatment significantly increased FSH levels compared to the PCOS group, but these remained lower than the control group.
- Letrozole-induced PCOS group exhibited increased body weight gain and ovarian weight compared to the control group.
- Denosumab treatment reduced body weight gain and ovarian weight compared to the PCOS group.

Conclusion

RANKL inhibitors can potentially prevent hormonal imbalance and ameliorate body and ovarian weight gain in letrozole-treated PCOS rat models.

Fact Check

- PCOS prevalence: The text states that approximately 5 to 15% of women are affected by PCOS globally.
- Letrozole dose: Letrozole was administered at a dose of 1 mg/kg orally for 21 days to induce PCOS.
- Denosumab dose and duration: Denosumab was given at 0.25 mg/kg body weight subcutaneously for 4 weeks.

Mind Map