120 Trilostane Effectively Reduces CL Progesterone Synthesis Prior to Acquisition of Luteolytic Sensitivity in Cyclic Gilts

Abstract

Abstract Understanding the mechanisms of luteolytic sensitivity (LS) is critical for identifying novel methods of controlling the reproductive cycle of livestock species. Uniquely, porcine corpora lutea (CL) remain unresponsive to the luteolytic effects of prostaglandinF2a (PGF) until days 12-13 of the estrous cycle. Previous data from our laboratory has demonstrated that luteal macrophages (MACs) play an active role in this process. It was hypothesized that suppressing progesterone (P4) production prior to LS would activate MACs and initiate LS. The objective of this study was to determine the optimal dose of Trilostane, (TRIL) a commercially available 3β-hydroxysteroid dehydrogenase inhibitor, to reduce luteal and serum P4 by a minimum of 80% and induce LS. Gilts received Matrix® for 14 days and then checked twice daily for estrus. At estrus (day 0), gilts were randomly assigned to receive the TRIL treatment (0,3,5,7.5,or 10mg/kg, n=2 per treatment) orally, every 12h for 36h starting on day 7 of the estrous cycle. Blood samples were taken every 12 hours on days 6 through 9 post estrus to measure P4 following treatment. Gilts were euthanized on day 9 of the estrous cycle, and CL tissue was frozen for P4 analysis. Progesterone concentrations were determined via RIA. Data were analyzed using a MIXED procedure of SAS and statistical significance was determined at P < 0.05 and a tendency at 0.05< P < 0.10. Serum P4 was reduced by 50% by 12h post treatment in all TRIL groups compared to control (P < 0.05). However, only the 10mg/Kg dose effectively reduced P4 by 80% compared to control (P < 0.05) and suppressed P4 throughout the treatment period. Luteal P4 was reduced by 72.4,82.4,87.7, and 88.6% compared to controls (P < 0.05) in treated with 3,5,7.5 and 10 mg/kg of TRIL, respectively. Collectively, oral administration of TRIL effectively reduced both serum and luteal P4, and the optimal dose of 10mg/Kg TRIL will be utilized in future studies addressing progesterone’s regulation of luteal macrophage, and their role in controlling LS.