Made available in DSpace on 2014-10-09T12:50:27Z (GMT). No. of bitstreams: 0 / Made available in DSpace on 2014-10-09T13:58:47Z (GMT). No. of bitstreams: 1 00629.pdf: 698191 bytes, checksum: 13b6a1876cd1e8729bc9cd5ae7842ff2 (MD5) / Dissertacao (Mestrado) / IEA/D / Instituto de Biociencias, Universidade de Sao Paulo - IB/USP

Made available in DSpace on 2014-10-09T12:50:27Z (GMT). No. of bitstreams: 0 / Made available in DSpace on 2014-10-09T13:58:47Z (GMT). No. of bitstreams: 1 00629.pdf: 698191 bytes, checksum: 13b6a1876cd1e8729bc9cd5ae7842ff2 (MD5) / Dissertacao (Mestrado) / IEA/D / Instituto de Biociencias, Universidade de Sao Paulo - IB/USP

Progesterone in the mare declines to almost undetectable concentrations in late gestation. It’s metabolized into several pregnanes, some circulating at very high concentrations. Although the function of many pregnanes remains unclear, 5α-dihydroprogesterone and allopregnanolone are bioactive. Measurements of pregnanes in late gestation are typically by immunoassay, although results are confounded by cross-reactivity with related pregnanes. Conversely, liquid chromatography tandem mass spectrometry (LC-MS/MS) allows differentiation of individual pregnanes. The purposes of these studies were: 1) to evaluate the ability of a 5α-reductase inhibitor, dutasteride, to alter pregnane metabolism and pregnancy outcome, 2) to evaluate changes in target pregnanes in late gestation by LC-MS/MS in mares with ascending placentitis, and 3) compare immunoassay and LC-MS/MS detection of pregnanes in late gestation. Our findings suggest that dutasteride significantly altered pregnane metabolism without effects on pregnancy outcome. Pregnane measurement by LC-MS/MS resulted in a significant (p<0.05) differences in assay results, while correlation was observed between immunoassay measurements and actual progesterone concentrations by LC-MS/MS. These studies demonstrate the complexity of pregnane metabolism in late gestation in the mare and the necessity of LC-MS/MS to detect specific changes that immunoassays cannot differentiate.