Bernd HOFFMANN, Sandra Goericke PESCH, Gerhard SCHULER

Antiprogestins; high potential compounds for use in veterinary research and therapy:

Progesteronun nükleer reseptörüne bağlanması transkripsiyonu uyarır. Antagonistler bu reseptöre yüksek affinite gösterirler ama oluşan sinyal iletim sistemi ya kısmen uyarılır ya da hiç uyarılmaz. Bir antagonistin spesifitesi hedef doku ve türe göre farklılık gösterir. Antagonistler mifepriston ve aglepriston için tam antagonist kapasite köpeklerde ve diğer türlerde gösterilmiştir. Progesteronun çok iyi tanımlanmış biyolojik aktiviteleri vardır, ancak birçok biyolojik olaydaki düzenleyici etkileri halen bilinmemektedir. Biz progesteronun köpeklerdeki yalancı gebelik ve luteal fonksiyonlardaki rolünü araştırdık. Bu rol köpeklerde açıkça gösterilirken, ineklerde karunkular progesteron reseptörlerinin uyarılması fötal membranların doğum öncesi olgulaşmasını ve retensiyonunu etkilemediği görülmüştür. Aglepristonun köpeklerde gebeliğin sonlandırılması amacıyla lisansı alınmıştır. Ancak, aglepriston gebeliğin dönemine bağlı olarak düzenleyici mekanizmaları bozar ve geç dönemdeki abortları kritik hale getirebilir. Köpeklerde etiket dışı olarak pyometra tedavisinde ve doğumun uyarılmasında kullanılmaktadır. Başarı için köpek trofoblastlarında Cox2 ekspresyonu verileri benzer şekilde göz önünde bulundurulmalıdır. Kedi, tavşan ve diğer türlerde de etiket dışı kullanımı vardır. Kedilerde antiprogesteronlar ile fibroadenomatozis tedavisi umut vericidir, ancak gebelik durumunda abort yan etkisi de düşünülmelidir. Fibroadenomatozis tedavisinde eksojen progesteron kullanımında bireysel dozajlama uygulanmalıdır.

Antiprogestinler; veteriner araştırma ve tedavide yüksek potansiyelli bileşikler: Derleme

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.

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