Parillo Francesco, Dall'Aglio Cecilia, Brecchia Gabriele, Maranesi Margherita, Polisca Angela, Boiti Cristiano, Zerani Massimo
Scuola di Scienze mediche veterinarie, Università di Camerino, Matelica, Italy.
Dipartimento di Scienze biopatologiche veterinarie ed Igiene delle produzioni animali e alimentari, Università di Perugia, Perugia, Italy.
Anim Reprod Sci. 2013 Apr;138(1-2):118-32. doi: 10.1016/j.anireprosci.2013.02.001. Epub 2013 Feb 16.
The study was designed to examine the aglepristone (RU534) mechanisms affecting the corpora lutea (CL) lifespan in pseudopregnant rabbits. Aglepristone (10 mg/kg b.w.) was injected subcutaneously twice at either early- or mid-luteal phase (Days 3 and 4, or Days 8 and 9, respectively) after induction of ovulation with GnRH (Day 0). Corpora lutea and uteri, explanted at days 6 and 11, were evaluated for immunohistochemistry and Western blotting of progesterone (PR) and estrogen (ER) receptors, cyclooxygenase 1 (COX1), COX2, and PGE2-9-ketoreductase (PGE2-9-K) enzymatic activities, and progesterone, PGF2α, and PGE2 in vitro synthesis. Independent of luteal stage, aglepristone prolonged the functional luteal phase by 3 Days over that of controls as assessed by blood progesterone profiles. Aglepristone decreased protein for ER during both luteal-stages in CL and uteri. Progesterone receptor protein was decreased by RU354 at Days 6 in the uterus and at Days 11 in CL, whereas RU534 increased PR at Days 11 in uteri. In the CL, RU534 enhanced progesterone production at Days 6 and 11, whereas it decreased PGF2α and increased PGE2 at Day 11. In the uteri, RU534 decreased PGF2α and increased PGE2 synthesis at both days. COX2 and PGE2-9K activities were decreased by RU534 in the CL at Day 11, whereas in the uteri COX2 increased and PGE2-9-K decreased at Days 6 and 11. In conclusion, these data on aglepristone effects suggest that progesterone has a regulatory role on luteal function through direct and uterine-mediated mechanisms in pseudopregnant rabbits.
本研究旨在探讨阿格列孕酮（RU534）影响假孕兔黄体（CL）寿命的机制。在用促性腺激素释放激素（GnRH，第0天）诱导排卵后的黄体早期或中期（分别为第3天和第4天，或第8天和第9天），皮下注射阿格列孕酮（10 mg/kg体重）两次。在第6天和第11天取出黄体和子宫，进行孕酮（PR）和雌激素（ER）受体、环氧化酶1（COX1）、COX2以及PGE2-9-酮还原酶（PGE2-9-K）酶活性的免疫组织化学和蛋白质印迹分析，并进行孕酮、PGF2α和PGE2的体外合成分析。与黄体阶段无关，通过血孕酮水平评估，阿格列孕酮使功能性黄体期比对照组延长3天。阿格列孕酮在黄体期的两个阶段均降低了CL和子宫中ER的蛋白水平。在子宫中，RU354在第6天降低了孕酮受体蛋白水平，在CL中第11天降低了该蛋白水平，而RU534在子宫中第11天增加了PR水平。在CL中，RU534在第6天和第11天增强了孕酮的产生，而在第11天降低了PGF2α并增加了PGE2。在子宫中，RU534在这两天均降低了PGF2α并增加了PGE2的合成。在第11天，RU534降低了CL中COX2和PGE2-9K的活性，而在子宫中，COX2在第6天和第11天增加，PGE2-9-K降低。总之，这些关于阿格列孕酮作用的数据表明，在假孕兔中，孕酮通过直接和子宫介导的机制对黄体功能具有调节作用。
