Session: OR46-Hyperandrogenemia: Influences & Implications
Room 121 (Moscone Center)
Hypothesis:We thus hypothesize that PCOS HA is triggered by ovarian NEFA overexposure and is improved following treatment with an AT2R agonist.
Methods: To test our hypothesis, experiments were conducted in 12 weeks old JCR:LA-cp/cp (cp) rats, which are characterized by visceral obesity, IR, HA and PCO. Cp rats (n=6) were compared to their controls (n=6), the JCR:LA +/? (+/?). Rats were treated for 8 days (intraperitoneal osmotic pumps) with saline or with the selective AT2R agonist C21/M24 (M24, 0.3 mg kg-1day-1). Rats underwent: 1) fasting sampling to measure total testosterone (TT; LC-MS/MS), NEFA (colorimetric assay) and insulin (ELISA) levels; and 2) an intravenous 18F-FTHA test to determine NEFA ovarian tissue uptake (Km).
Results: Weight and food intake were not modified by treatment. Compared to controls, saline-treated PCOS/cp rats displayed higher insulin (0.29±0.09 vs.4.27±1.85 ng/mL; p<0.001), TT (0.05±0.03 vs. 0.12±0.03 nM; p=0.05), NEFA (0.46±0.18 vs 1.26±0.25 mM; p=0.04), and Km (14.6±2.2 vs. 24.5±15.7 nmol·g‑1 min‑1; p=0.20). As compared to saline, ovarian Km was significantly improved in M24-treated +/? rats (11.5±2.1 nmol·g‑1 min‑1; p=0.035), but no changes were observed for insulin (0.37±0.184 ng/mL; p=0.32), TT levels (0.09±0.05 nM; p=0.24) and NEFA (0.66±0.14 mM; p=0.11). In cp rats, M24 treatment did not significantly improved insulin (2.93±1.54 ng/mL; p=0.32), but normalized TT (0.05±0.02 nM; p=0.01), NEFA (0.79±0.19 mM; p<0.01) and Km (10.9±4.7 nmol·g‑1 min‑1; p=0.03), in comparison to saline treated cp rats. A positive correlation was observed between TT and NEFA (Spearman r=0.58; p<0.05) and TT and Km (0.75; p=0.02) in cprats, but not in control rats.
Conclusion: In our PCOS rat model, ovarian NEFA uptake and TT levels are strongly associated and are both significantly and predominantly reduced following selective AT2R agonist therapy. Our project provides new information on the role of NEFAs in PCOS hyperandrogenemia and suggests a role for AT2R agonist in the treatment of PCOS.
Nothing to Disclose: SL, CN, MCB, DFV, NG, AC, JPB
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