Mehmet Bertan YILMAZ, Mehmet Ali ERKOÇ, Sabriye KOCATÜRK-SEL, Erdal TUNÇ, Lütfiye ÖZPAK, Ayfer PAZARBAŞI, Ali İrfan GÜZEL, Davut ALPTEKİN, Hüsnü Ümit LÜLEYAP, Osman DEMİRHAN, Mülkiye KASAP, Halil KASAP

Gelişmekte Olan Fare Fetüs Beyninde Aromataz, Östrojen Reseptör Alfa ve Progesteron Reseptörünün Birbirleriyle Olan İlişkileri

Amaç: Bu çalışmadaki amacımız, gonodotropin salgılanması, cinsel dimorfik fetal beyin gelişimi ve yetişkinlerdeki cinsel tercih için çok önemli olan, aromatazın ve östrojen reseptör alfa (Esr1) ve progesteron reseptörlerinin (Pgr) gebeliğin farklı dönemlerindeki mRNA ekspresyon profillerinin eş zamanlı olarak belirlenmesidir. Yöntem: Dişi fareler, üreme potansiyeli olan erkek farelerle çiftleştirildi ve başarılı çiftleşme, bir gün sonra oluşan vajinal plak kontrol edilerek doğrulandı (vajinal plak=gebeliğin birinci günü). Gebeliğin 9-12-15-17-19-21. günlerinde gebe farelerin yaşamları sonlandırıldı ve fetüslere ait beyinler çıkarılarak mRNA izole edildi ve cDNA haline çevrildi. mRNA ekspresyon düzeylerinin belirlenmesi Cyp19a1, Esr1 ve Pgr genlerine özgün primerler ile real time PCR yöntemi kullanılarak gerçekleştirildi. Bulgular: Çalışmalarımızda; Esr1 ve Pgr mRNA ekspresyon düzeyleri 9. günde tepe noktaya ulaştı, 17-18. günlerde ise normal yetişkin düzeylerine döndü. Cyp19a1 mRNA ekspresyonu, Esr1 ve Pgr mRNA düzeylerindeki ciddi bir azalmayla beraber, 15-16. günde tepe noktaya ulaştı ve takriben doğumun olacağı dönemlerde normal erişkin seviyelerine indi. Sonuç: Fetal beyinde Cyp19a1 ekspresyonu gebeliğin 11-12. günü civarında başlar ve 15-16. günlerinde tepe noktasına ulaşır. Bunu takiben 19-20. günlerinde de normal yetişkin seviyelerine iner. Son zamanlarda rapor edilen çalışmalarda, Esr1 ve Pgr"nin fare beyninde Cyp19a1 mRNA ekspresyonunun düzenlenmesinde rol oynadığı belirtilmiştir. Bu çalışmalar ışığında bizim bulgularımız, Esr1 ve Pgr"nin fetal fare beyninde aromataz ekspresyonun düzenlenmesinde rol oynadığını düşündürebilir.

Anahtar Kelimeler:

Aromataz, beyin, fare, fetüs, östrojen reseptör alfa, progesteron reseptörü

Interrelation of aromatase, estrogen receptor alpha and progesterone receptor in the developing mouse fetal brain

Purpose: Aromatase (Cyp19a1) is crucial for the sexually dimorphic development of the fetal brain, regulation of gonadotropin secretion and sexual interest in adults. Our goal is to determine the developmental mRNA expression patterns of aromatase, estrogen receptor alpha (Esr1) and progesterone receptor (Pgr) in the fetal mouse brain at different times of gestation. Methods: Female mice were mated with fertile males and checked for vaginal plug the next day to confirm successful mating (vaginal plug=day 1 of pregnancy). At gestational days 9-12-15-17-19-21 pregnant mice were sacrificed and fetal brains were removed and mRNAs were isolated and reverse transcribed into cDNAs. In order to evaluate mRNA expression levels, real time PCR was performed employing primers for Cyp19a1, Esr1 and Pgr genes. Results: In our studies, Esr1 and Pgr mRNA expression levels peaked at day 9 and returned to normal adult levels at around day 17-18. Cyp19a1 mRNA expression peaked at day 14-16 along with a drastic decrease in Esr1 and Pgr mRNA expression levels and then returned to normal adult levels around the time of delivery. Conclusion: Cyp19a1 expression in the fetal brain launches around gestational day 11-12 and peaks around gestational day 14-16 and fall back to normal adult levels at around gestational day 19-20. It has been recently reported that Esr1 and Pgr both mediate Cyp19a1 mRNA expression in the mouse brain. Together with these previous reports, our findings may imply that both Esr1 and Pgr possibly play a role in the developmental regulation of aromatase in the fetal mouse brain.

Keywords:

aromatase, brain, estrogen receptor alpha, fetal, mouse, progesterone receptor,

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Yazışma Adresi / Address for Correspondence: Dr. Mehmet Bertan Yılmaz Çukurova Üniversitesi Tıp Fakültesi Tıbbi Biyoloji ve Genetik Anabilim Dalı ADANA Tel: 0322 3386060/3498 e-mail: mehmetbertanyilmaz@gmailo.com geliş tarihi/received :09.08.2012 kabul tarihi/accepted:05.10.2012