17β-Östradiolün Overioktomize Ratlarda Spontan Myometriyal Kasılımlar Üzerine Etkisi

Çalışma farklı doz ve sürelerde uygulanan 17ß-östradiolün ovaryumları çıkarılmış sıçanlarda spontan myometriyal kasılımlar üzerine etkisinin belirlenmesi amaçlamaktadır. Araştırmada 3-6 aylık ve ortalama 270 ± 20 g ağırlığında, 72 adet Sprague Dawley cinsi dişi sıçanlar kullanılmıştır. Sıçanlar, her grupta 18 sıçan bulunacak şekilde, kontrol (Ov) ve 3 deneme gurubuna (östrojen) ayrılmıştır. Kontrol grubuna günlük olarak kas içi susam yağı enjeksiyonları yapılmış (0,2 ml), birinci deneme grubundaki sıçanlara günlük 25 µg 17ß-östradiol, ikinci deneme gurubundaki sıçanlara günlük 50 µg 17ß- östradiol, ve üçüncü deneme gurubundaki sıçanlara günlük 100 µg 17ß-östradiol kas içi uygulanmıştır. Her grup kendi arasında 3 alt gruba ayrılarak 18, 90 ve 162. saatlerde 6’şar hayvan genel ötenazi yapılmıştır. Nitrik oksitin etkinliğinin belirlenmesi amacıyla L-Arginin SNP ve L-NNA (Nitro-N-Arginin) uygulaması yapıldı. Alınan uterus örneklerinden elde edilen doku kesitlerinde cGMP-PK1 ekspirasyonunu göstermek için immunohistokimyasal yöntemle boyandı. Uygulama sonrası östrojen verilen gruplarda spontan myometriyal kasılımların şiddeti, östrojenin dozuna ve süresine bağlı olarak arttı. Ayrıca, östrojenin L-arginin-NOS-NO-cGMP yolunun etkinliğini engellediği belirlendi. Östrojenin uterusta bulunan longiditunal düz kaslarda cGMP-PK1 ekspirasyonu üzerine etkisinin bulunmadığı görüldü. Sonuç olarak östrojenin doza ve süreye bağımlı olarak uterus kasılımlarının şiddetini artırırken, L-Arginin-NOS-NO- cGMP-PK1 yolunun etkinliğini engellediği fakat bu engellenmenin cGMP-PK1 üzerinden olmadığı belirlenmiştir.

Anahtar Kelimeler:

17β-östradiol, Myometriyum, CGMP’ye bağımlı protein kinaz, NOS

Effects of 17β-Estradiol on Spontaneous Myometrial Contractions in Overiectomized Rats

The aim of this study was to evaluate the effect of injecting different doses and time intervals of 17β-estradiol on spontaneous myometrial contractions of ovariectomized rats. Three to 6 months old 72 female Sprague Dawley rats, weighing 270 ± 20 g, were used in the current study. The ovariectomized rats were randomly assigned to a control (Ov) and three experimental groups (17β-estradiol injected) of 18 rats each. Rats in the Ov group received daily sesame oil (0.2 ml, IM), whereas each rat in the three experimental groups was treated with daily 25, 50 and 100 μg estradiol (IM), respectively. Each group was further divided into 3 subgroups: 6 rats in each group were sacrificed by cervical dislocation at 18, 90 and 162 hr. In order to determine endogenous nitric oxide activity, the L-arginine solution was used. Sodium nitroprusside (SNP) was used for evaluation of the exogenous nitric oxide pathway. In addition, L-NNA (nitro-N-arginine) treatment was applied in order to determine the effect of endogenous NO at the receptor level. Immunohistochemical evaluation was performed to determine the cGMP-PK1 expression from the uterus samples. In the current study, estrogen treatment increased spontaneous myometrial contraction in a dose and time-dependent manner. Moreover, estrogen treatments inhibited L-arginine-NOS-NO-cGMP pathway. On the other hand, estrogen failed to have any effect on cGMP-PK1 expression in uterine longitudinal smooth muscles. Thus, 17β-estradiol treatments increased the uterine smooth muscle cell contractions. The treatments also inhibited L-Arginine-NOS-NO-cGMP-PK1 pathway. However, our results indicated that 17β-estradiol did not show its effect through cGMP-PK1.

Keywords:

17β-estradiol, myometrium, cGMP-dependent protein kinase, NOS,

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