Journal of Advanced Biomedical Sciences
مجله علوم زیست پزشکی پیشرفته
J Adv Biomed Sci.
Medical Sciences
http://jabs.fums.ac.ir
1
admin
2228-5105
2783-1523
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8888
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en
jalali
1399
5
1
gregorian
2020
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online
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fulltext
en
تاثیر ال دوپا و بلوکه کردن گیرنده های دوپامینی بر بیان ژن آروماتاز و غلظت سرمی LH در سندروم تخمدان پلی کیستیک مدل موش های صحرایی (مقاله انگلیسی)
Influences of L-DOPA and Blocking Dopamine Receptors on Aromatase Gene Expression and Serum Concentration of LH in Rat Model of Polycystic Ovary Syndrome
غدد
Endocrinology
پژوهشي
Research
<div style="text-align: justify;"><strong><span style="font-family:B Nazanin;"><span style="font-size:10.0pt;">زمینه و هدف:</span></span></strong><span style="font-family:B Nazanin;"><span style="font-size:10.0pt;"> سندروم تخمدان پلی کیستیک</span></span><span style="font-family:B Nazanin;"><span style="font-size:10.0pt;">(</span></span><span dir="LTR"><span style="font-family:Times New Roman,serif;"><span style="font-size:8.0pt;">PCOS</span></span></span><span style="font-family:B Nazanin;"><span style="font-size:10.0pt;">) </span></span><span style="font-family:B Nazanin;"><span style="font-size:10.0pt;">با سطوح بالای آندروژن­ها، نسبت </span></span><span dir="LTR"><span style="font-family:Times New Roman,serif;"><span style="font-size:8.0pt;">LH/FSH</span></span></span><span style="font-family:B Nazanin;"><span style="font-size:10.0pt;">، فعالیت پایین آروماتاز و مسیر پیام­رسانی دوپامینرژیکی همراه است.</span></span> <span style="font-family:B Nazanin;"><span style="font-size:10.0pt;">در تحقیق حاضر، </span></span><span style="font-family:B Nazanin;"><span style="font-size:10.0pt;">اثرات ال</span></span><span style="font-family:B Nazanin;"><span style="font-size:10.0pt;">­</span></span><span style="font-family:B Nazanin;"><span style="font-size:10.0pt;">دوپا و آنتاگونیست</span></span><span style="font-family:B Nazanin;"><span style="font-size:10.0pt;">­</span></span><span style="font-family:B Nazanin;"><span style="font-size:10.0pt;">های گیرنده دوپامین </span></span><span style="font-family:B Nazanin;"><span style="font-size:10.0pt;">بر </span></span><span style="font-family:B Nazanin;"><span style="font-size:10.0pt;">بیان ژن</span></span><span style="font-family:B Nazanin;"><span style="font-size:10.0pt;">­</span></span> <em><span style="font-family:B Nazanin;"><span style="font-size:10.0pt;">آروماتاز</span></span></em><em><span style="font-family:B Nazanin;"><span style="font-size:10.0pt;">(</span></span></em><em><span dir="LTR"><span style="font-family:Times New Roman,serif;"><span style="font-size:8.0pt;">Cyp19</span></span></span></em><em><span style="font-family:B Nazanin;"><span style="font-size:10.0pt;">)</span></span></em><span style="font-family:B Nazanin;"><span style="font-size:10.0pt;"> و غلظت سرمی </span></span><span dir="LTR"><span style="font-family:Times New Roman,serif;"><span style="font-size:8.0pt;">LH</span></span></span> <span style="font-family:B Nazanin;"><span style="font-size:10.0pt;">در </span></span><span style="font-family:B Nazanin;"><span style="font-size:10.0pt;">موش­های صحرایی مدل </span></span><span dir="LTR"><span style="font-family:Times New Roman,serif;"><span style="font-size:8.0pt;">PCOS</span></span></span> <span style="font-family:B Nazanin;"><span style="font-size:10.0pt;">بررسی شد</span></span><span style="font-family:B Nazanin;"><span style="font-size:10.0pt;">.</span></span><span style="font-family:B Nazanin;"><span style="font-size:10.0pt;"> </span></span><br>
<strong><span style="font-family:B Nazanin;"><span style="font-size:10.0pt;">مواد و روش­ ها:</span></span></strong><span style="font-family:B Nazanin;"><span style="font-size:10.0pt;"> بعد از القای </span></span><span dir="LTR"><span style="font-family:Times New Roman,serif;"><span style="font-size:8.0pt;">PCOS</span></span></span><span style="font-family:B Nazanin;"><span style="font-size:10.0pt;"> با </span></span><span style="font-family:B Nazanin;"><span style="font-size:10.0pt;"> استرادیول والرات</span></span><span style="font-family:B Nazanin;"><span style="font-size:10.0pt;">، موش­های صحرایی </span></span><span dir="LTR"><span style="font-family:Times New Roman,serif;"><span style="font-size:8.0pt;"> PCOS</span></span></span> <span style="font-family:B Nazanin;"><span style="font-size:10.0pt;">سالین، </span></span><span dir="LTR"><span style="font-family:Times New Roman,serif;"><span style="font-size:8.0pt;">mg/kg</span></span></span><span style="font-family:B Nazanin;"><span style="font-size:10.0pt;">100</span></span><span style="font-family:B Nazanin;"><span style="font-size:10.0pt;"> ال دوپا یا تزریق همزمان </span></span><span dir="LTR"><span style="font-family:Times New Roman,serif;"><span style="font-size:8.0pt;">mg/kg</span></span></span><span style="font-family:B Nazanin;"><span style="font-size:10.0pt;">10</span></span><span style="font-family:B Nazanin;"><span style="font-size:10.0pt;">سولپرید،</span></span> <span dir="LTR"><span style="font-family:Times New Roman,serif;"><span style="font-size:8.0pt;">mg/kg</span></span></span><span style="font-family:B Nazanin;"><span style="font-size:10.0pt;"> 1</span></span> <span dir="LTR"><span style="font-family:Times New Roman,serif;"><span style="font-size:8.0pt;">SCH23390 </span></span></span><span style="font-family:B Nazanin;"><span style="font-size:10.0pt;"> و </span></span><span dir="LTR"><span style="font-family:Times New Roman,serif;"><span style="font-size:8.0pt;">mg/kg</span></span></span><span style="font-family:B Nazanin;"><span style="font-size:10.0pt;"> 100</span></span><span style="font-family:B Nazanin;"><span style="font-size:10.0pt;">ال دوپا </span></span><span style="font-family:B Nazanin;"><span style="font-size:10.0pt;">را </span></span><span style="font-family:B Nazanin;"><span style="font-size:10.0pt;">دریافت کردند</span></span><span style="font-family:B Nazanin;"><span style="font-size:10.0pt;">. </span></span><span style="font-family:B Nazanin;"><span style="font-size:10.0pt;">پنج </span></span><span style="font-family:B Nazanin;"><span style="font-size:10.0pt;">موش صحرایی سالم </span></span><span style="font-family:B Nazanin;"><span style="font-size:10.0pt;">در مرحله استروس </span></span><span style="font-family:B Nazanin;"><span style="font-size:10.0pt;">به عنوان گروه کنترل</span></span><span style="font-family:B Nazanin;"><span style="font-size:10.0pt;"> استفاده شد. غلظت سرمی </span></span><span dir="LTR"><span style="font-family:Times New Roman,serif;"><span style="font-size:8.0pt;">LH</span></span></span><span style="font-family:B Nazanin;"><span style="font-size:10.0pt;"> و </span></span><span style="font-family:B Nazanin;"><span style="font-size:10.0pt;">بیان نسبی ژن<em> آروماتاز</em></span></span> <span style="font-family:B Nazanin;"><span style="font-size:10.0pt;">با به ترتیب با روش رادیوایمنواسی و ریل تایم </span></span><span dir="LTR"><span style="font-family:Times New Roman,serif;"><span style="font-size:8.0pt;">PCR</span></span></span><span style="font-family:B Nazanin;"><span style="font-size:10.0pt;"> اندازه­گیری شدند. </span></span><span dir="LTR"><span style="font-family:Times New Roman,serif;"><span style="font-size:8.0pt;"></span></span></span><br>
<strong><span style="font-family:B Nazanin;"><span style="font-size:10.0pt;">نتایج:</span></span></strong><span style="font-family:B Nazanin;"><span style="font-size:10.0pt;"> میانگین سطوح </span></span><span dir="LTR"><span style="font-family:Times New Roman,serif;"><span style="font-size:8.0pt;">mRNA</span></span></span><span style="font-family:B Nazanin;"><span style="font-size:10.0pt;">ی <em>آروماتاز</em> در هیپوتالاموس و تخمدان</span></span> <span style="font-family:B Nazanin;"><span style="font-size:10.0pt;">گروه</span></span> <span dir="LTR"><span style="font-family:Times New Roman,serif;"><span style="font-size:8.0pt;">PCOS</span></span></span><span style="font-family:B Nazanin;"><span style="font-size:10.0pt;"> در مقایسه با گروه سالم کاهش معنی­دار و</span></span><span style="font-family:B Nazanin;"><span style="font-size:10.0pt;"> میانگین </span></span><span style="font-family:B Nazanin;"><span style="font-size:10.0pt;">غلظت سرمی </span></span><span dir="LTR"><span style="font-family:Times New Roman,serif;"><span style="font-size:8.0pt;">LH</span></span></span><span style="font-family:B Nazanin;"><span style="font-size:10.0pt;"> در گروه </span></span><span dir="LTR"><span style="font-family:Times New Roman,serif;"><span style="font-size:8.0pt;">PCOS</span></span></span><span style="font-family:B Nazanin;"><span style="font-size:10.0pt;"> در مقایسه با گروه سالم افزایش معنی­دار پیدا کرد. </span></span><span style="font-family:B Nazanin;"><span style="font-size:10.0pt;">ال</span></span><span style="font-family:B Nazanin;"><span style="font-size:10.0pt;">­</span></span><span style="font-family:B Nazanin;"><span style="font-size:10.0pt;">دوپا</span></span><span style="font-family:B Nazanin;"><span style="font-size:10.0pt;"> بیان نسبی <em>آروماتاز</em> هیپوتالاموسی و تخمدانی را در مقایسه با گروه </span></span><span dir="LTR"><span style="font-family:Times New Roman,serif;"><span style="font-size:8.0pt;">PCOS</span></span></span><span style="font-family:B Nazanin;"><span style="font-size:10.0pt;"> به طور معنی­داری افزایش و </span></span><span style="font-family:B Nazanin;"><span style="font-size:10.0pt;">میانگین </span></span><span style="font-family:B Nazanin;"><span style="font-size:10.0pt;">غلظت سرمی </span></span><span dir="LTR"><span style="font-family:Times New Roman,serif;"><span style="font-size:8.0pt;">LH</span></span></span> <span style="font-family:B Nazanin;"><span style="font-size:10.0pt;">را در مقایسه با گروه </span></span><em><span dir="LTR"><span style="font-family:Times New Roman,serif;"><span style="font-size:8.0pt;">PCOS</span></span></span></em> <span style="font-family:B Nazanin;"><span style="font-size:10.0pt;">به طور معنی­داری کاهش داد. آنتاگونیست­های</span></span><span style="font-family:B Nazanin;"><span style="font-size:10.0pt;"> گیرنده</span></span><span style="font-family:B Nazanin;"><span style="font-size:10.0pt;">­</span></span><span style="font-family:B Nazanin;"><span style="font-size:10.0pt;">های دوپامین </span></span><span style="font-family:B Nazanin;"><span style="font-size:10.0pt;">شامل </span></span><span style="font-family:B Nazanin;"><span style="font-size:10.0pt;">سولپرید و </span></span><span dir="LTR"><span style="font-family:Times New Roman,serif;"><span style="font-size:8.0pt;">SCH23390 </span></span></span><span style="font-family:B Nazanin;"><span style="font-size:10.0pt;"> اثرات تحریکی ال­دوپا بر بیان ژن <em>آروماتاز</em> در هیپوتالاموس و اثرات مهاری آن بر غلظت سرمی هوررمون </span></span><span dir="LTR"><span style="font-family:Times New Roman,serif;"><span style="font-size:8.0pt;">LH</span></span></span> <span style="font-family:B Nazanin;"><span style="font-size:10.0pt;">را بلوکه کرد<em>.</em> </span></span><span style="font-family:B Nazanin;"><span style="font-size:10.0pt;">ولی </span></span><span style="font-family:B Nazanin;"><span style="font-size:10.0pt;"> سولپرید و </span></span><span dir="LTR"><span style="font-family:Times New Roman,serif;"><span style="font-size:8.0pt;">SCH23390 </span></span></span> <span style="font-family:B Nazanin;"><span style="font-size:10.0pt;">اثرات تحریکی ال دوپا بر بیان ژن <em>آروماتاز</em> تخمدانی را مهار نکردند. </span></span><br>
<strong><span style="font-family:B Nazanin;"><span style="font-size:10.0pt;">نتیجه ­گیری:</span></span></strong><span style="font-family:B Nazanin;"><span style="font-size:10.0pt;"> ال دوپا از طریق کاهش ترشح </span></span><span dir="LTR"><span style="font-family:Times New Roman,serif;"><span style="font-size:8.0pt;">LH</span></span></span><span style="font-family:B Nazanin;"><span style="font-size:10.0pt;"> و افزایش بیان</span></span> <span style="font-family:B Nazanin;"><span style="font-size:10.0pt;">ژن <em>آروماتاز</em> ممکن است در کنترل وضعیت </span></span><span dir="LTR"><span style="font-family:Times New Roman,serif;"><span style="font-size:8.0pt;">PCOS</span></span></span><span style="font-family:B Nazanin;"><span style="font-size:10.0pt;"> دخالت داشته باشد.</span></span> </div>
<div style="text-align: justify;"><strong><em>Background & Objective:</em></strong> Polycystic ovary syndrome (PCOS) is associated with higher plasma levels of androgens, LH/FSH ratio and lower activity of aromatase and dopaminergic signaling pathways. In the present study, the effects of L-DOPA and dopamine receptor antagonists were investigated on <em>aromatase (Cyp19)</em> gene expression and LH concentration in PCOS rat model. <span dir="RTL"></span><br>
<strong><em>Material & Methods:</em></strong> Following PCOS induction by estradiol valerate, The PCOS rats received saline, L-DOPA(100mg/kg) or simultaneous injections of sulpride (10mg/kg)/ SCH23390 (1mg/kg)/ L-DOPA (100mg/kg). Five intact estrous rats were used as a control group. Mean serum LH concentration and<em> aromatase</em> relative gene expression was evaluated by radioimmonoassay and real- time-PCR method respectively. <span dir="RTL"></span><br>
<strong><em>Results</em></strong><em>:</em> Mean <em>aromatase</em> mRNA levels significantly decreased in the hypothalamus and ovary of PCOS model rats compared to intact ones. Mean serum LH concentration significantly increased in PCOS group in comparison with intact rats. The L-DOPA significantly increased mean hypothalamic and ovarian <em>aromatase</em> gene expression compared to PCOS rats while it significantly declined serum LH concentration compared to PCOS rats. Dopamine receptor antagonists including sulpiride and SCH23390 blocks the stimulatory or inhibitory effects of L-DOPA on hypothalamic <em>aromatase</em> or serum LH levels respectively. But the sulpride and SCH23390 did not inhibit the stimulatory influences of L-DOPA on ovarian <em>aromatase</em> gene expression.<br>
<strong><em>Conclusion:</em></strong> L-DOPA may be involved in the controling of PCOS condition via decreasing LH secretion and increasing the <em>aromatase</em> gene expresion.<br>
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</div>
آروماتاز, الدوپا, سولپرید, SCH23390, مدل حیوانی PCOS
aromatase, L-DOPA, sulpride, SCH23390, PCOS animal model
2448
2455
http://jabs.fums.ac.ir/browse.php?a_code=A-10-2445-1&slc_lang=en&sid=1
khadijeh
Haghighat gollo
خدیجه
حقیقت گللو
Kh.haghighat94@gmail.com
100319475328460022960
100319475328460022960
No
Faculty of Sciences, University of Mohaghegh Ardabili, Ardabil, Iran
دانشکده علوم، دانشگاه محقق اردبیلی، اردبیل، ایران
Fariba
Mahmoudi
فریبا
محمودی
f.mahmoudi@uma.ac.ir
100319475328460022961
100319475328460022961
Yes
Faculty of Sciences, University of Mohaghegh Ardabili, Ardabil, Iran
دانشکده علوم، دانشگاه محقق اردبیلی، اردبیل، ایران
Abolfazl
Bayrami
ابوالفضل
بایرامی
a_bayrami@uma.ac.ir
100319475328460022962
100319475328460022962
No
Faculty of Sciences, University of Mohaghegh Ardabili, Ardabil, Iran
دانشکده علوم، دانشگاه محقق اردبیلی، اردبیل، ایران
Saber
Zahri
صابر
زهری
zahri@uma.ac.ir
100319475328460022963
100319475328460022963
No
Faculty of Sciences, University of Mohaghegh Ardabili, Ardabil, Iran
دانشکده علوم، دانشگاه محقق اردبیلی، اردبیل، ایران