2011, Cilt 27, Sayı 2, Sayfa(lar) 077-086
Antiprogestins; high potential compounds for use in veterinary research and therapy: A review
Bernd Hoffmann, Sandra Goericke-Pesch, Gerhard Schuler
Clinic for Obstetrics, Gynecology and Andrology of Large and Small Animals, Justus-Liebig-University Giessen, Germany
Keywords: Antiprogestins, therapy, research
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Progesterone binding to its nuclear receptor leads to the initiation of transcription. Antagonists show a high binding affinity to the receptor, the resulting signaling cascade, however, is incomplete with transcription not or partially induced. Specificity of a full/partial antagonist may vary, depending on the species and tissue targeted. For the antiprogestins mifepristone and aglepristone full antagonistic activity has been demonstrated in the dog and other species. Progesterone exhibits well defined biological activities. However, its participation as a regulatory factor in many biological processes is still unknown. We have assessed the role of progesterone in overt pseudopregnany and control of luteal function in the bitch. Its involvement could be clearly demonstrated while interaction with caruncular progesterone receptors in the cow seems not to affect prepartal maturation and retention of foetal membranes. Aglepristone has been licensed for termination of pregnancy in the dog. However, depending on the stage of pregnancy, it interferes with different regulatory mechanisms, making induction of late abortion a critical issue. Off-label use in the dog is for conservative treatment of pyometra and induction of parturition. To be successful, again a critical approach is necessary and recent data on the expression of Cox2 in the canine trophoblast must be considered. Off-label use with similar indications is in the cat, rabbit and other species. In the cat treatment of fibroadenomatosis with antiprogestins is highly promising; however, in case of a pregnancy abortion must be expected. An individual dose regimen must be applied when fibroadenomatosis was induced by exogenous progesterone treatment.