DOCSLIB.ORG

The Effect of Intrahippocampal Injection of Diarylpropionitrile, a Selective Estrogen Receptor-Β Agonist, on Passive Avoidance Learning

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
The Effect of Intrahippocampal Injection of Diarylpropionitrile, a Selective Estrogen Receptor-Β Agonist, on Passive Avoidance Learning Physiology and Pharmacology, 12 (4), 254 - 260 Winter 2009 [Article in Persian] The effect of intrahippocampal injection of diarylpropionitrile, a selective estrogen receptor-β agonist, on passive avoidance learning Zeinab Sharifkhodaei 1,2, Nasser Naghdi 2*, Shahrbanoo Oryan 3, Parichehr Yaghmaei 1 1. Dept. Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran 2. Dept. Physiology and Pharmacology, Pasteur Institute of Iran, Tehran, Iran 3. Dept. Biology, Tarbiat Moalem University, Tehran, Iran Received: 5 Mar 2008 Revised: 23 Aug 2008 Accepted: 25 Aug 2008 Abstract* Introduction: Neurohormones like testosterone and estradiol have an important role in learning and memory. The hippocampus is essentially involved in learning and memory, and is known to be a target for estradiol actions. Estrogen receptors (ERs) are highly expressed in CA1 of rat hippocampus, and mediate the effects of estrogen on learning and memory. Estradiol receptor belong to a family of transcription factors, the nuclear receptor superfamily, and has two subtypes ERα and ERβ. The current research has been conducted to assess the effect of ERβ selective agonist, diarylpropionitrile (DPN), on passive avoidance of adult male rats, by using passive avoidance task. Methods: Male adult rats were bilaterally cannulated into the CA1 area of hippocampus, and then received vehicle (dimethyl sulfoxide, DMSO) or DPN (0.2, 0.5, 1 µg/0.5µl/side), 30 min before training on passive avoidance task. Results: The results showed that pre-training intra-CA1 injections of DPN (0.5, 1 µg/0.5µl/side), significantly decreased step-through latencies and increased time spent in dark on passive avoidance learning (P<0.01). Conclusion: Our dataArchive suggest that intra-CA1 administration of of DPN couldSID impair learning and memory acquisition on passive avoidance task. Keywords: Estradiol; Estradiol receptor β; passive avoidance learning; Rat. * Corresponding author e- mail: [email protected] [email protected] Available online @: www.phypha.ir/ppj 32 www.SID.ir ﻓﻴﺰﻳﻮﻟﻮژي و ﻓﺎرﻣﺎﻛﻮﻟﻮژي 12 (4)، 254 – 260 زﻣﺴﺘﺎن 1387 ﻓﻴﺰﻳﻮﻟﻮژي و ﻓﺎرﻣﺎﻛﻮﻟﻮژي ﺟﻠﺪ 12، ﺷﻤﺎرة 4، زﻣﺴﺘﺎن 1387 ﺗﺎﺛﻴﺮﺗﺰرﻳﻖ درون ﻫﻴﭙﻮﻛﻤﭙﻲ DPN (آﮔﻮﻧﻴﺴﺖ اﺧﺘﺼﺎﺻﻲ ﮔﻴﺮﻧﺪ هي ﺑﺘﺎ اﺳﺘﺮادﻳﻮل) ﺑﺮﺣﺎﻓﻈﻪ و ﻳﺎدﮔﻴﺮي اﺟﺘﻨﺎﺑﻲ ﻏﻴﺮﻓﻌﺎل در ﻣﻮش ﺻﺤﺮاﻳﻲ زﻳﻨﺐ ﺷﺮﻳﻒ ﺧﺪاﻳﻲ2،1، ﻧﺎﺻﺮ ﻧﻘﺪي2*، .ﺷﻬﺮﺑﺎﻧﻮ ﻋﺮﻳﺎن3، ﭘﺮﻳﭽﻬﺮ ﻳﻐﻤﺎﻳﻲ1 1. ﮔﺮوه زﻳﺴﺖﺷﻨﺎﺳﻲ، داﻧﺸﻜﺪه ﻋﻠﻮم، واﺣﺪ ﻋﻠﻮم و ﺗﺤﻘﻴﻘﺎت، داﻧﺸﮕﺎه آزاد اﺳﻼﻣﻲ، ﺗﻬﺮان 2. ﮔﺮوه ﻓﻴﺰﻳﻮﻟﻮژي و ﻓﺎرﻣﺎﻛﻮﻟﻮژي، اﻧﻴﺴﺘﻴﺘﻮ ﭘﺎﺳﺘﻮر، ﺗﻬﺮان 3. ﮔﺮوه زﻳﺴﺖﺷﻨﺎﺳﻲ، داﻧﺸﻜﺪه ﻋﻠﻮم، داﻧﺸﮕﺎه ﺗﺮﺑﻴﺖ ﻣﻌﻠﻢ، ﺗﻬﺮان درﻳﺎﻓﺖ: 14 ﺷﻬﺮﻳﻮر 87 ﺑﺎزﺑﻴﻨﻲ: 5 آﺑﺎن 87 ﭘﺬﻳﺮش: 22 آﺑﺎن 87 ERβ و ﻳﺎدﮔﻴﺮي اﺟﺘﻨﺎﺑﻲ ﻏﻴﺮﻓﻌﺎل ﺷﺮﻳﻒ ﺧﺪاﻳﻲ و ﻫﻤﻜﺎران ﭼﻜﻴﺪه ﻣﻘﺪﻣﻪ: ﻧﻮروﻫﻮرﻣﻮن ﻫﺎ ﻫﻤﺎﻧﻨﺪ ﺗﺴﺘﻮﺳﺘﺮون و اﺳﺘﺮادﻳﻮل ﻧﻘﺶ ﻣﻬﻤﻲ در ﻳﺎدﮔﻴﺮي و ﺣﺎﻓﻈﻪ ﺑﺮ ﻋﻬﺪه دارﻧﺪ. ﻫﻴﭙﻮﻛﺎﻣﭗ ﻧﻴﺰ ﺑﻄﻮر اﺳﺎﺳـﻲ در ﻳـﺎدﮔﻴﺮي و ﺣﺎﻓﻈـﻪ دﺧﺎﻟـﺖ دارد و ﺑﻌﻨﻮان اﻧﺪام ﻫﺪف ﺑﺮاي ﻋﻤﻠﻜﺮدﻫﺎي اﺳﺘﺮادﻳﻮل ﺷﻨﺎﺧﺘﻪ ﺷﺪه اﺳﺖ. ﮔﻴﺮﻧﺪ هﻫﺎي اﺳﺘﺮوژﻧﻲ(ERs) ﺑﻄﻮر ﻣﺘﺮاﻛﻢ در ﻧﺎﺣﻴﻪ CA1 ﻫﻴﭙﻮﻛﺎﻣﭗ رت ﺑﻴﺎن ﻣﻲﺷـﻮﻧﺪ و ﺗـﺎﺛﻴﺮات اﺳـﺘﺮاد ﻳﻮل ﺑﺮ ﻳﺎدﮔﻴﺮي و ﺣﺎﻓﻈﻪ را ﻣﻴﺎﻧﺠﻲﮔﺮي ﻣﻲﻛﻨﻨﺪ. ﮔﻴﺮﻧﺪه ﻫﺎي اﺳﺘﺮوژن ﻣﺘﻌﻠﻖ ﺑﻪ ﺧﺎﻧﻮاده ﻓﺎﻛﺘﻮرﻫﺎي روﻧﻮﻳﺴﻲ، ﻓﻮق ﺧﺎﻧﻮاده ﮔﻴﺮﻧﺪ هﻫﺎي ﻫﺴﺘ ﻪاي، ﻫﺴـﺘﻨﺪ و ﺑـﻪ دو ﻧـﻮع α و β ﺗﻘﺴـﻴﻢ ﻣﻲﺷﻮﻧﺪ. در اﻳﻦ ﻣﻄﺎﻟﻌﻪ، ﺗﺎﺛﻴﺮآﮔﻮﻧﻴﺴﺖ اﺧﺘﺼﺎﺻﻲ DPN) ,diarylpropionitrile, ERβ) ﺑﺮ ﻳﺎدﮔﻴﺮي اﺟﺘﻨﺎﺑﻲ ﻏﻴﺮﻓﻌﺎل در رت ﻫﺎي ﻧﺮ ﺑﺎﻟﻎ در دﺳـﺘﮕﺎه اﺟﺘﻨـﺎﺑ ﻲ ﻏﻴﺮﻓﻌـﺎل ﻣـﻮرد ﺑﺮرﺳﻲ ﻗﺮار ﮔﺮﻓﺘ ﻪاﺳﺖ. روشﻫﺎ: رتﻫﺎي ﻧﺮ ﺑﺎﻟﻎ ﺑﻄﻮر دو ﻃﺮﻓﻪ در ﻧﺎﺣﻴﻪ CA1 ﻫﻴﭙﻮﻛﺎﻣﭗ ﻛﺎﻧﻮ لﮔﺬاري ﺷـﺪﻧﺪ در ﮔـﺮوه ﻛﻨﺘـﺮل dimethyl sulfoxide) DMSO) ﺧـﺎﻟﺺ و در ﮔـﺮوه ﺗﺠﺮﺑـﻲ دوزﻫﺎي 2/0 و 5/0 و 1 ﻣﻴﻜﺮوﮔﺮم DPN ﺣﻞ ﺷﺪه در5/0ﻣﻴﻜﺮوﻟﻴﺘﺮ DMSO ﺗﻬﻴﻪ ﺷﺪ و 30 دﻗﻴﻘﻪ ﻗﺒﻞ از آﻣﻮزش در دﺳﺘﮕﺎه اﺟﺘﻨﺎﺑﻲ ﻏﻴﺮﻓﻌﺎل ﺑﻪ آﻧﻬﺎ ﺗﺰرﻳﻖ ﺷﺪ. ﻳﺎﻓﺘﻪﻫﺎ: ﻧﺘﺎﻳﺞ ﻧﺸﺎن دادﻧﺪ ﻛﻪ ﺗﺰرﻳﻖ دوزﻫﺎي 5/0 و 1 ﻣﻴﻜﺮوﮔﺮم DPN ﻗﺒﻞ از آﻣﻮزش در ﻧﺎﺣﻴﻪ CA1، ﺑﻄﻮر ﻣﻌﻨﻲداري زﻣﺎن ﺗـﺎﺧﻴﺮ در ورود ﺑـﻪ اﺗـﺎق ﺗﺎرﻳـ ﻚ را ﻛـﺎﻫﺶ ﻣﻲدﻫﻨﺪ و ﻣﻮﺟﺐ اﻓﺰاﻳﺶ ﻣﺪت زﻣﺎن ﺣﻀﻮر در اﺗﺎق ﺗﺎرﻳﻚ ﻣﻲﺷﻮﻧﺪ (P<0.01). ﻧﺘﻴﺠﻪﮔﻴﺮي: اﻳﻦ اﻃﻼﻋﺎت ﭘﻴﺸﻨﻬﺎد ﻣﻲﻛﻨﻨﺪ ﻛﻪ ﺗﺰرﻳﻖ DPN در ﻧﺎﺣﻴﻪ CA1 ﺑﺎﻋﺚ ﺗﺨﺮﻳﺐ ﻳﺎدﮔﻴﺮي و ﺣﺎﻓﻈﻪ ﻣﻲﺷﻮد. ﭘـﺲ ﮔﻴﺮﻧـﺪ هي ﺑﺘـﺎي اﺳـﺘﺮادﻳﻮل ﻧﻘـﺶ ﻣﻬﻤـﻲ در ﻳﺎدﮔﻴﺮي و ﺣﺎﻓﻈﻪ اﺟﺘﻨﺎﺑﻲ ﻏﻴﺮ ﻓﻌﺎل ﺑﺮ ﻋﻬﺪه دارد.Archive of SID واژهﻫﺎي ﻛﻠﻴﺪي: اﺳﺘﺮادﻳﻮل، ﮔﻴﺮﻧﺪه ﺑﺘﺎي اﺳﺘﺮادﻳﻮل، ﻳﺎدﮔﻴﺮي اﺟﺘﻨﺎﺑﻲ ﻏﻴﺮ ﻓﻌﺎل ﻣﻘﺪﻣﻪ* آﻧﺪروﺳــﺘﻨﺪﻳﻮن (AD)، ﺗﺴﺘﻮﺳــﺘﺮون و اﺳــﺘﺮادﻳﻮل از ﻛﻠﺴــﺘﺮول در ﻣﻐـــﺰ ﺳـــﺎﺧﺖ دﻫﻴـــﺪرواﭘﻲ آﻧﺪروﺳـــﺘﺮون (DHEA)، درون زا ﮔﺰارش ﺷﺪه اﺳﺖ [25،18]. ﻣﻄﺎﻟﻌﺎت اﺧﻴﺮ ﻧﺸﺎن داده اﻧﺪ ﻛﻪ ﻧﻮرون ﻫﺎي ﻫﻴﭙﻮﻛﺎﻣـﭗ ﺑـﺎ ﻣﺠﻤﻮﻋـﻪ اي از آﻧـﺰﻳﻢﻫـﺎ ﺳـﺎﺧﺖ اﺳﺘﺮادﻳﻮل و ﺗﺴﺘﻮﺳﺘﺮون از ﻛﻠﺴﺘﺮول را ﻛﺎﺗﺎﻟﻴﺰ ﻣﻲﻛﻨﻨﺪ [27،18]. * ﻧﻮﻳﺴﻨﺪة ﻣﺴﺌﻮل ﻣﻜﺎﺗﺒﺎت: [email protected] [email protected] ﻏﻠﻈﺖ ﭘﺎﻳﻪ اﺳﺘﺮادﻳﻮل در ﻫﻴﭙﻮﻛﺎﻣﭗ ﺣـﺪوداً nM 1 اﺳـﺖ ﻛـﻪ از وﺑﮕﺎه ﻣﺠﻠﻪ: www.phypha.ir/ppj ﻣﻴﺰان آن در ﭘﻼﺳﻤﺎي ﺧﻮن ﺑﻴﺸﺘﺮ اﺳﺖ [28]. 254 www.SID.ir ﻓﻴﺰﻳﻮﻟﻮژي و ﻓﺎرﻣﺎﻛﻮﻟﻮژي ﺟﻠﺪ 12، ﺷﻤﺎرة 4، زﻣﺴﺘﺎن 1387 ﺷــﻮاﻫﺪي وﺟــﻮد دارد ﻛــﻪ اﺳــﺘﺮوﺋﻴﺪﻫﺎي ﮔﻨــﺎدي ﻣﺜــﻞ ﺿﺮوري اﺳﺖ. ﻳﺎدﮔﻴﺮي و ﺣﺎﻓﻈﻪ از ﺟﻤﻠﻪ ﺣﺎﻓﻈـﻪ ﻣﺮﺟـﻊ ﺗﻮﺳـﻂ ﺗﺴﺘﻮﺳــﺘﺮون، اﺳــﺘﺮادﻳﻮل، دي ﻫﻴﺪروﺗﺴﺘﻮﺳــﺘﺮون و ﭘﺮﮔﻨﻨﻮﻟــﻮن اﺳﺘﺮادﻳﻮل ﺗﺨﺮﻳﺐ ﻣﻲﺷﻮد. در ﻣﻘﺎﺑﻞ، ﺳﻄﺢ ﭘﺎﺋﻴﻨﻲ از اﺳـﺘﺮادﻳﻮل ﺑﺮدﺳﺘﮕﺎه ﻋﺼﺒﻲ ﻣﺮﻛﺰي اﺛﺮاﺗﻲ را اﻋﻤﺎل ﻣﻲﻛﻨﻨـﺪ [35]. ﺗـﺮاﻛﻢ ﻣﻤﻜﻦ اﺳﺖ ﺑﺎﻋﺚ ﺑﻬﺒﻮد ﺣﺎﻓﻈﻪ ﺟﺎري ﺷﻮد [33]. ﺑﺮﺧﻲ ﻣﻄﺎﻟﻌﺎت ﺑﺎﻻي ﮔﻴﺮﻧﺪ هﻫﺎي اﺳﺘﺮوژن و آﻧﺪروژن در ﻣﺮاﻛﺰ ﺑﻨﻴﺎدي ﻳﺎدﮔﻴﺮي ﻧﺸﺎن ﻣﻲدﻫﻨﺪ ﻛﻪ ERβ ﻳﻚ ﺗﻌﺪﻳﻞ ﻛﻨﻨﺪه ﻣﻬﻢ ﺗﻜﺜﻴﺮ ﺳـﻠﻮﻟﻲ و و ﺣﺎﻓﻈﻪ در ﻣﻐﺰ، ﻣﺜﻞ ﻫﻴﭙﻮﻛﺎﻣﭗ، ﻧﺸـﺎن ﻣـ ﻲدﻫـﺪ ﻛـﻪ اﺣﺘﻤـﺎﻻً ﺣﺎﻓﻈﻪ و ﻳﺎدﮔﻴﺮي اﺳﺖ [9]. در ﻣـﻮش ﻫـﺎﻳﻲ ﻛـﻪ درآﻧﻬـﺎ ERβ رواﺑﻄﻲ ﺑﻴﻦ ﮔﻴﺮﻧﺪه ﻫﺎي آﻧﺪروژن و اﺳﺘﺮوژن وﺟﻨﺒﻪ ﻫـﺎي ادراﻛـ ﻲ ﺣﺬف ﺷﺪه اﺳﺖ ﻳﺎدﮔﻴﺮي و ﺣﺎﻓﻈﻪ اﻛﺘﺴﺎﺑﻲ در ﻣﺎز آﺑﻲ ﻣـﻮرﻳﺲ دﺳﺘﮕﺎه ﻋﺼﺒﻲ ﻣﺮﻛﺰي ﺑﺮﻗﺮار اﺳﺖ [20،16]. در ﻣﻘﺎﻳﺴــﻪ ﺑــﺎ ﮔــﺮوه ﻛﻨﺘــﺮل ﺗﺨﺮﻳــﺐ ﺷــﺪه اﺳــﺖ [33]. اﺧﻴــﺮاً اﺛﺮات ﻫﻮرﻣﻮن ﻫـﺎي اﺳـﺘﺮوﺋ ﻴﺪي ﺗﻮﺳـﻂ ﮔﻴﺮﻧـﺪ هﻫـﺎي درون درﮔﺰارﺷﻲ ﭘﻴﺸﻨﻬﺎد ﺷﺪه اﺳﺖ ﻛﻪ ﻣﻮ شﻫﺎي ﻣﺎد هاي ﻛـﻪ در آﻧﻬـﺎ ﺳـﻠﻮ ﻟ ﻲ وﻳــﮋهاي در ﺑﺎﻓــﺖ ﻫــﺪف ﻣﻴـ ﺎﻧﺠﻲﮔــﺮي ﻣــ ﻲﺷــﻮد، ﻛــﻪ ERβ ﺣﺬف ﺷﺪه اﺳﺖ ﺳﻄﻮح ﺑﺎﻻرﻓﺘﻪ اي از اﺿـﻄﺮاب و ﺳـﻄﻮح ﻛﻤﭙﻠﻜﺲ ﻫﺎي اﺳﺘﺮوﺋﻴﺪ- ﮔﻴﺮﻧـﺪه ﻧﻘـﺶ ﻣﺮﻛـﺰي در ﺑﻜـﺎرﮔﻴﺮي ﺗﻘﻠﻴﻞ ﻳﺎﻓﺘﻪ اي از ﻓﻌﺎﻟﻴـ ﺖ را در آزﻣـﻮن ﻫـﺎي ﺑـﺎز از ﺧـﻮد ﻧﺸـﺎن ﻣﻜﺎﻧﻴﺴﻢﻫﺎي ﺳﻠﻮﻟﻲ ﻻزم ﺑﺮاي ﻓﻌـﺎل ﻛـﺮدن روﻧﻮﻳﺴـﻲ ژن ﺑـﺮ ﻣﻲدﻫﻨﺪ [21]، در ﺣﺎﻟﻴﻜﻪ ﻳﺎﻓﺘـﻪ ﻫـﺎي ﮔﺬﺷـﺘﻪ ﻧ ﺸـﺎن ﻣـ ﻲدﻫﻨـﺪ ﻋﻬﺪه دارﻧﺪ [8]. ﮔﻴﺮﻧﺪه ﻫﺎي اﺳـﺘﺮاد ﻳﻮل (ERs) ﺑﻄـﻮر ﻏﺎﻟـﺐ در ﻣﻮش ﻫﺎي ﻣﺎده اي ﻛﻪ در آﻧﻬﺎ ﮔﻴﺮﻧﺪه آﻟﻔﺎ اﺳﺘﺮادﻳﻮل ﺣـﺬف ﺷـﺪه ﺳﻴﺴﺘﻢ ﻟﻴﻤﺒﻴﻚ ﻣﺜﻞ آﻣﻴﮕـﺪال، ﺳـﭙﺘﻮم، ﻫﻴﭙﻮﻛﺎﻣـﭗ و ﻫﻤﭽﻨـﻴﻦ اﺳﺖ در آزﻣﻮن اﺟﺘﻨﺎﺑﻲ ﻏﻴﺮ ﻓﻌﺎل ﻳـ ﺎدﮔﻴﺮي ﺧـﻮﺑﻲ ﻧﺪارﻧـﺪ [12]. ﻫﻴﭙﻮﺗﺎﻻﻣﻮس ﻣﺘﻤﺮﻛﺰ ﺷﺪه اﻧـﺪ و در ﻣﺮاﺣـﻞ اﺣﺴﺎﺳـ ﻲ وادراﻛـﻲ اﻳﻦ ﻳﺎﻓﺘﻪ ﻫﺎ ﻣﺎ را ﺑﻪ اﻳـ ﻦ ﻓﻜـﺮ ﻣـ ﻲاﻧﺪازﻧـﺪ ﻛـﻪ دو ﻧـﻮع ﮔﻴﺮﻧـﺪه دﺧﺎﻟﺖ دارﻧـﺪ [37،29،1]. ﮔﻴﺮﻧـﺪه ﻫـﺎي اﺳـﺘﺮاد ﻳﻮل ﺑـﻪ ﺧـﺎﻧﻮاده اﺳﺘﺮادﻳﻮل اﻧﻮاع ﻣﺨﺘﻠﻔﻲ از ﺣﺎﻓﻈﻪ و ﻳﺎدﮔﻴﺮي را درﮔﻴﺮ ﻣﻲﻛﻨﻨـﺪ، ﻓﺎﻛﺘﻮرﻫﺎي روﻧﻮﻳﺴﻲ و ﻓﻮق ﺧﺎﻧﻮاده ﮔﻴﺮﻧﺪه ﻫﺎي ﻫﺴﺘﻪ اي ﻣﺘﻌﻠـﻖ ﻣﻤﻜﻦ اﺳﺖ ERα ﺑﺮاي ﻳﺎدﮔﻴﺮي اﺣﺴﺎﺳﻲ ﻛﻪ ﺑﻴﺸﺘﺮ ﻣﺮﺑـﻮط ﺑـﻪ ﻫﺴﺘﻨﺪ [23،22] و ﺑﻪ دو ﺗﻴﭗ ﮔﻴﺮﻧﺪه اﺳﺘﺮادﻳﻮﻟﻲ آﻟﻔﺎ و ﺑﺘﺎ ﺗﻘﺴـﻴﻢ آﻣﻴﮕﺪال ﻣﻲﺷـﻮد ﺿـﺮوري ﺑﺎﺷـﺪ در ﺣﺎﻟﻴﻜـﻪ ﻳـ ﺎدﮔﻴﺮي ﻓﻀـﺎﻳﻲ ﻣﻲﺷﻮﻧﺪ [5]. در ﺳـﺎل 1996 دوﻣـﻴﻦ ﺗﻴـﭗ ﮔﻴﺮﻧـﺪه اﺳـﺘﺮادﻳﻮل، واﺑﺴﺘﻪ ﺑﻪ ﻫﻴﭙﻮﻛﺎﻣﭗ ﺑﻪ ERβ ﻧﻴﺎز دارد [33]. ERβ، از ﭘﺮوﺳﺘﺎت و ﺗﺨﻤﺪان ﻣـﻮش ﺻـﺤﺮاﺋﻲ ﺟـﺪا ﺷـﺪ [22]. اﻳﻦ اﻃﻼﻋﺎت ﻣﺎ را ﺑﺮ آن داﺷﺖ ﺗـﺎ ﺑـﺎ اﺳـﺘﻔﺎده از آﮔﻮﻧﻴﺴـﺖ ﻣﺘﻌﺎﻗﺒﺎً اﻳﻦ ﮔﻴﺮﻧﺪه ﺗـﺎزه ي اﺳـﺘﺮادﻳﻮل در ﻣـﻮش [38] و اﻧﺴـﺎن اﺧﺘﺼﺎﺻﻲ ﮔﻴﺮﻧﺪه ي ﺑﺘﺎي اﺳـﺘﺮادﻳﻮل ﺑـﻪ ﺑﺮرﺳـﻲ ﻧﻘـﺶ آن در ﻛﺸﻒ ﺷﺪ [26]. اﻳﻦ دو ﻧﻮع ﮔﻴﺮﻧـﺪه اﺳـﺘﺮوژﻧﻲ ﺗﻮﺳـﻂ ژ نﻫـﺎي ﻣﻨﻄﻘﻪ CA1 ﻫﻴﭙﻮﻛﺎﻣﭗ ﻣﻮش ﻫﺎي ﺻﺤﺮاﺋﻲ ﻧﺮ ﺑـﺎﻟﻎ در دﺳـﺘﮕﺎه ﺟﺪاﮔﺎﻧﻪ اي ﻛﺪ ﻣﻲﺷﻮﻧﺪ (ﮔﻴﺮﻧﺪه آﻟﻔﺎ اﺳﺘﺮادﻳﻮل ﺗﻮﺳﻂ ﻛﺮوﻣـﻮزوم اﺟﺘﻨﺎﺑﻲ ﻏﻴﺮ ﻓﻌﺎل ﺑﭙﺮدازﻳﻢ. 6 و ﺑﺘﺎ ﺗﻮﺳﻂ ﻛﺮوﻣﻮزوم 14) و اﻳﺰوﻓﺮم ﻳﻜﺪﻳﮕﺮ ﻧﻴﺴـﺘﻨﺪ [38]. در اﻧﺴﺎن ﻣﻘﺪار ﻧﺴﺒﺘﺎً زﻳﺎدي از ERβ در ﻫﻴﭙﻮﻛﺎﻣﭗ، ﻗﺸﺮ، ﻛﻼﺳﺘﺮوم ﻣﻮاد و روشﻫﺎ ﻳﺎﻓﺘﻪ ﺷﺪه اﺳﺖ، در ﺣﺎﻟﻴﻜﻪ، ﺑﺮ ﺧﻼف ERα، ﻣﻘﺪار ﻛﻤﺘﺮي از آن در ﻫﻴﭙﻮﺗــﺎﻻﻣﻮس و آﻣﻴﮕــﺪال وﺟــﻮد دارد [29]. در ﭘﺮﻳﻤﺎدﻫــﺎ و ﻣﻮش ﻫﺎي ﺻﺤﺮاﺋﻲ ﻧﺮ ﺑﺎﻟﻎ ﻧﮋاد وﻳﺴـﺘﺎر (200 -250 ﮔﺮﻣـﻲ) از ﺟﻮﻧﺪﮔﺎن ﻫﺮ دو ﻧـﻮع ﮔﻴﺮﻧـﺪه اﺳـﺘﺮادﻳﻮل، آﻟﻔـﺎ و ﺑﺘـﺎ در ﻧـﻮاﺣﻲ ﺑﺨﺶ ﭘﺮورش و ﺗﻜﺜﻴﺮ ﻣﻮﺳﺴﻪ ﭘﺎﺳﺘﻮر اﻳﺮان ﺗﻬﻴﻪ ﺷﺪ. ﺣﻴﻮاﻧـﺎت در ﻣﺨﺘﻠﻔﻲ از ﻣﻐﺰ ﻳﺎﻓﺖ ﻣﻲﺷـﻮﻧﺪ، در ﻫﻴﭙﻮﻛﺎﻣـﭗ SIDﻧﺴـﺒﺖ ﺑـﺎﻻﻳﻲ ازof ﺷﺮاﻳﻂ 12 ﺳﺎﻋﺖ روﺷـﻨﺎﻳﻲ و Archive12ﺳـﺎﻋﺖ ﺗـﺎرﻳﻜﻲ (روﺷـﻨﺎﻳﻲ از 7 ERβ/ERα وﺟﻮد دارد [31،14،1]. ﺻﺒﺢ) و دﻣﺎي 2 ± 23 درﺟﻪ ﺳﺎﻧﺘ ﻲﮔﺮاد ﻧﮕﻬـﺪاري ﺷـﺪﻧﺪ و آب و دﻳﺪه ﺷﺪه اﺳﺖ ﻛﻪ اﺳﺘﺮادﻳﻮل اﺛﺮات ﺣﺎدي ﺑﺮ ﻫﻴﭙﻮﻛﺎﻣﭗ دارد ﻏﺬا ﺑﻪ ﻣﻘﺪار ﻛﺎﻓﻲ در اﺧﺘﻴﺎر آﻧﻬﺎ ﻗﺮار ﮔﺮﻓﺖ. در اﻳﻦ ﻣﻄﺎﻟﻌﻪ ﻣﻄﺎﺑﻖ و ﺑﺎﻋﺚ ﺑﺎﻻ رﻓﺘﻦ ﺣﺎﻓﻈﻪ ﻓﻀﺎﻳﻲ ﻣـﻲ ﺷـﻮد ﻛـﻪ ﻣﻤﻜـﻦ اﺳـﺖ از ﺑﺎ ﺗﻮﺻﻴﻪ ﻫﺎي ﺑﻴﺎﻧﻴﻪ ي Helsinki و ﻗـﻮاﻧﻴﻦ ﭘﺬﻳﺮﻓﺘـﻪ ﺷـﺪ هي ﺑـﻴﻦ ﻃﺮﻳﻖ ﻓﻌﺎﻟﻴﺖﻫﺎي ژﻧﻮﻣﻴﻚ ﮔﻴﺮﻧﺪه ﻫﺎي اﺳﺘﺮادﻳﻮل ﺑﺎﺷﺪ [30]. ﻫﺮ اﻟﻤﻠﻠﻲ در ارﺗﺒﺎط ﺑﺎ ﺣﻴﻮاﻧﺎت آزﻣﺎﻳﺸﮕﺎﻫﻲ، ﺑﺎ ﺣﻴﻮاﻧﺎت رﻓﺘﺎر ﺷﺪ. دو ﻧﻮع ﮔﻴﺮﻧـﺪه ﺧـﺎرج ﻫﺴـﺘﻪ اي ERβ و ERα در ﻫﻴﭙﻮﻛﺎﻣـﭗ و 7-8 روز ﻗﺒﻞ از اﻧﺠﺎم آزﻣﺎﻳﺶ رﻓﺘﺎري ﺣﻴﻮاﻧﺎت ﺗﺤﺖ ﺟﺮاﺣﻲ آﻣﻴﮕﺪال ﻣﺘﻤﺮﻛﺰ ﺷﺪه اﻧﺪ، دو ﻣﻨﻄﻘﻪ اي ﻛـﻪ ﺗﻨﻈـﻴﻢ ﻛﻨﻨـﺪه ﻫـﺎي ﻗــﺮار ﻣــ ﻲﮔﺮﻓﺘﻨــﺪ. ﻣﺨﻠــﻮﻃﻲ از ﻛﺘــﺎﻣﻴﻦ (mg/Kg, i.p 100) و ﻣﻬﻤﻲ ﺑﺮاي ﻳﺎدﮔﻴﺮي و ﺣﺎﻓﻈﻪ ﻫﺴﺘﻨﺪ [19]. زاﻳﻠــﻮزﻳﻦ (mg/Kg, i.p 25) ﺑﺼــﻮرت درون ﺻــﻔﺎﻗﻲ ﺑﻤﻨﻈــﻮر اﺳﺘﺮادﻳﻮل ﺑﺮاي ﺑﺴﻴﺎري از رﻓﺘﺎرﻫﺎ از ﺟﻤﻠﻪ رﻓﺘﺎرﻫﺎي ادراﻛﻲ ﺑﻴﻬﻮش ﻛﺮدن ﺣﻴﻮاﻧﺎت ﺗﺰرﻳﻖ ﺷـﺪ [10،25]. ﺳـﭙﺲ ﺑﺼـﻮرت دو 255 www.SID.ir ERβ و ﻳﺎدﮔﻴﺮي اﺟﺘﻨﺎﺑﻲ ﻏﻴﺮﻓﻌﺎل ﺷﺮﻳﻒ ﺧﺪاﻳﻲ و ﻫﻤﻜﺎران ﻃﺮﻓﻪ در ﻣﻨﻄﻘﻪ ﺑﺎﻻي CA1 ﺑﺎ اﺳﺘﻔﺎده از اﻃﻠـﺲ ﭘﺎﻛﺴـﻴﻨﻮس و ﻣﻴﻠﻲ آﻣﭙﺮو ﻣﺪت 5/1 ﺛﺎﻧﻴﻪ) ﺑﻪ ﻛﻒ دﺳﺖ و ﭘﺎﻫﺎي ﺣﻴﻮان داده واﺗﺴﻮن (AP:-3.8mm از ﺑﺮﮔﻤﺎ، ML: ±2.2mm از ﺧﻂ وﺳـﻂ ﻣﻲ ﺷﺪ 5 ﺛﺎﻧﻴﻪ ﭘﺲ از ﺷﻮك درب ﮔﻴﻮﺗﻴﻨﻲ ﺑـﺎز ﺷـﺪه و زﻣـﺎن و DV: -2.7mm از ﺳﻄﺢ ﺟﻤﺠﻤﻪ) ﻛﺎﻧﻮ لﮔﺬاري ﺷﺪ. دوﭘـﻴﭻ در ﺧﺮوج ﻣﻮش ﻣﺤﺎﺳﺒﻪ ﻣﻲ ﮔﺮدد. ﭘﺲ از ﺧﺮوج ﺣﻴﻮان 120 ﺛﺎﻧﻴﻪ اﻃﺮاف ﻛﺎﻧﻮل ﻫﺎ در ﺟﻤﺠﻤﻪ ﺑﺮاي ﺛﺎﺑﺖ ﻧﮕﻪ داﺷـﺘﻦ ﻛـﺎﻧﻮل ﻗـﺮار ﺑﻪ او اﺟﺎزه داده ﻣﻲ ﺷﺪ ﺗﺎ در ﻗﺴﻤﺖ روﺷﻦ ﺑﺎﻗﻲ ﺑﻤﺎﻧـﺪ، ﻋـﺪم دادهﺷﺪ و ﺗﻮﺳﻂ ﺳﻴﻤﺎن دﻧﺪاﻧﭙﺰﺷﻜﻲ ﻣﺤﻜﻢ ﺷﺪﻧﺪ. ورود ﺣﻴﻮان ﺑﻪ ﻧﺎﺣﻴﻪ ﺗﺎرﻳﻚ ﺑﻪ ﻣـﺪت 120 ﺛﺎﻧﻴـﻪ ﺑـﻪ ﻋﻨـﻮان ﺗﺰرﻳﻖ درون ﻫﻴﭙﻮﻛﺎﻣﭗ از ﻃﺮﻳﻖ ﻛﺎﻧﻮل ﻫﺎ ﺗﻮﺳﻂ ﺳﻮز نﻫـﺎي ﻳﺎدﮔﻴﺮي (اﻛﺘﺴﺎب) ﻣﻮﻓﻖ در ﻧﻈﺮ ﮔﺮﻓﺘﻪ ﻣـﻲ ﺷـﺪ.
Load more

Recommended publications
  • TE INI (19 ) United States (12 ) Patent Application Publication ( 10) Pub
    US 20200187851A1TE INI (19 ) United States (12 ) Patent Application Publication ( 10) Pub . No .: US 2020/0187851 A1 Offenbacher et al. (43 ) Pub . Date : Jun . 18 , 2020 ( 54 ) PERIODONTAL DISEASE STRATIFICATION (52 ) U.S. CI. AND USES THEREOF CPC A61B 5/4552 (2013.01 ) ; G16H 20/10 ( 71) Applicant: The University of North Carolina at ( 2018.01) ; A61B 5/7275 ( 2013.01) ; A61B Chapel Hill , Chapel Hill , NC (US ) 5/7264 ( 2013.01 ) ( 72 ) Inventors: Steven Offenbacher, Chapel Hill , NC (US ) ; Thiago Morelli , Durham , NC ( 57 ) ABSTRACT (US ) ; Kevin Lee Moss, Graham , NC ( US ) ; James Douglas Beck , Chapel Described herein are methods of classifying periodontal Hill , NC (US ) patients and individual teeth . For example , disclosed is a method of diagnosing periodontal disease and / or risk of ( 21) Appl. No .: 16 /713,874 tooth loss in a subject that involves classifying teeth into one of 7 classes of periodontal disease. The method can include ( 22 ) Filed : Dec. 13 , 2019 the step of performing a dental examination on a patient and Related U.S. Application Data determining a periodontal profile class ( PPC ) . The method can further include the step of determining for each tooth a ( 60 ) Provisional application No.62 / 780,675 , filed on Dec. Tooth Profile Class ( TPC ) . The PPC and TPC can be used 17 , 2018 together to generate a composite risk score for an individual, which is referred to herein as the Index of Periodontal Risk Publication Classification ( IPR ) . In some embodiments , each stage of the disclosed (51 ) Int. Cl. PPC system is characterized by unique single nucleotide A61B 5/00 ( 2006.01 ) polymorphisms (SNPs ) associated with unique pathways , G16H 20/10 ( 2006.01 ) identifying unique druggable targets for each stage .
    [Show full text]
  • New Insights for Hormone Therapy in Perimenopausal Women Neuroprotection
    Chapter 12 New Insights for Hormone Therapy in Perimenopausal Women Neuroprotection Manuela Cristina Russu and Alexandra Cristina Antonescu Additional information is available at the end of the chapter http://dx.doi.org/10.5772/intechopen.74332 Abstract Perimenopause is a mandatory period in women’s life, when the medical staff may initiate hormone therapy with sex steroids for the delay of brain aging and neurodegenerative diseases, during the so-called “window of opportunity.” Animals’ models are helpful to sustain the still controversial results of human clinical observational and/or randomized controlled studies. Estrogens, progesterone, and androgens, with their nuclear and mem- brane receptors, genes, and epigenetics, with their connections to cholinergic, GABAergic, serotoninergic, and glutamatergic systems are involved in women’snormalbrainorin brain’s pathology. The sex steroids are active through direct and/or indirect mechanisms to modulate and/or to protect brain plasticity, and vessels network, fuel metabolism—glucose, ketones, ATP, to reduce insulin resistance, and inflammation of the aging brain through blood-brain barrier disruption, microglial aberrant activation, and neural cell survival/loss. Keywords: perimenopause, “window” of opportunity, neuroprotection, sex steroid hormones 1. Introduction The months/years of perimenopause represent an important moment during women’saging, when sex steroids and their receptors decline are evident in the hippocampal and cortical neu- rons, after estrogen exposure during the reproductive years. The sex steroid hormones decline is associated/acts synergic to other factors as hypertension, diabetes, hypoxia/obstructive sleep apnea, obesity, vitamin B12/folate deficiency, depression, and traumatic brain injury to promote diverse pathological mechanisms involved in brain aging, memory impairment, and AD.
    [Show full text]
  • Estrogen Receptor Beta Is a Negative Regulator of Mammary Cell Proliferation Xiaozheng Song University of Vermont
    University of Vermont ScholarWorks @ UVM Graduate College Dissertations and Theses Dissertations and Theses 2014 Estrogen Receptor Beta Is A Negative Regulator Of Mammary Cell Proliferation Xiaozheng Song University of Vermont Follow this and additional works at: https://scholarworks.uvm.edu/graddis Part of the Animal Sciences Commons, and the Molecular Biology Commons Recommended Citation Song, Xiaozheng, "Estrogen Receptor Beta Is A Negative Regulator Of Mammary Cell Proliferation" (2014). Graduate College Dissertations and Theses. 259. https://scholarworks.uvm.edu/graddis/259 This Dissertation is brought to you for free and open access by the Dissertations and Theses at ScholarWorks @ UVM. It has been accepted for inclusion in Graduate College Dissertations and Theses by an authorized administrator of ScholarWorks @ UVM. For more information, please contact [email protected]. ESTROGEN RECEPTOR BETA IS A NEGATIVE REGULATOR OF MAMMARY CELL PROLIFERATION A Dissertation Presented by Xiaozheng Song to The Faculty of the Graduate College of The University of Vermont In Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy Specializing in Animal Science October, 2014 Accepted by the Faculty of the Graduate College, The University of Vermont, in partial fulfillment of the requirements for the degree of Doctor of Philosophy, specializing in Animal Science. Dissertation Examination Committee: ____________________________________ Advisor Zhongzong Pan Ph.D. ____________________________________ Co-Advisor Andre-Denis Wright Ph.D. ____________________________________ Rona Delay, Ph.D. ____________________________________ David Kerr, Ph.D. ____________________________________ Chairperson Karen M. Lounsbury, Ph. D. ____________________________________ Dean, Graduate College Cynthia J. Forehand, Ph.D. Date: May 5, 2014 ABSTRACT The mammary gland cell growth and differentiation are under the control of both systemic hormones and locally produced growth factors.
    [Show full text]
  • Estriol Therapy for Autoimmune and Neurodegenerative Diseases and Disorders
    (19) TZZ¥Z__T (11) EP 3 045 177 A1 (12) EUROPEAN PATENT APPLICATION (43) Date of publication: (51) Int Cl.: 20.07.2016 Bulletin 2016/29 A61K 31/565 (2006.01) A61K 31/566 (2006.01) A61K 31/568 (2006.01) A61K 45/06 (2006.01) (2006.01) (2006.01) (21) Application number: 16000349.7 A61K 31/785 A61P 25/00 (22) Date of filing: 26.09.2006 (84) Designated Contracting States: (72) Inventor: Voskuhl, Rhonda R. AT BE BG CH CY CZ DE DK EE ES FI FR GB GR Los Angeles, CA 90024 (US) HU IE IS IT LI LT LU LV MC NL PL PT RO SE SI SK TR (74) Representative: Müller-Boré & Partner Patentanwälte PartG mbB (30) Priority: 26.09.2005 US 720972 P Friedenheimer Brücke 21 26.07.2006 US 833527 P 80639 München (DE) (62) Document number(s) of the earlier application(s) in Remarks: accordance with Art. 76 EPC: This application was filed on 11-02-2016 as a 13005320.0 / 2 698 167 divisional application to the application mentioned 06815626.4 / 1 929 291 under INID code 62. (71) Applicant: The Regents of the University of California Oakland, CA 94607 (US) (54) ESTRIOL THERAPY FOR AUTOIMMUNE AND NEURODEGENERATIVE DISEASES AND DISORDERS (57) The present invention relates to a dosage from comprising estriol and glatiramer acetate polymer-1 for use in the treatment of multiple sclerosis (MS), as well as to a kit comprising estriol and glatiramer acetate polymer-1. EP 3 045 177 A1 Printed by Jouve, 75001 PARIS (FR) EP 3 045 177 A1 Description [0001] This invention was made with Government support under Grant No.
    [Show full text]
  • Decreases Breast Cancer Cell Survival by Regulating the IRE1&Sol
    Oncogene (2015) 34, 4130–4141 © 2015 Macmillan Publishers Limited All rights reserved 0950-9232/15 www.nature.com/onc ORIGINAL ARTICLE ERβ decreases breast cancer cell survival by regulating the IRE1/XBP-1 pathway G Rajapaksa1, F Nikolos1, I Bado1, R Clarke2, J-Å Gustafsson1 and C Thomas1 Unfolded protein response (UPR) is an adaptive reaction that allows cancer cells to survive endoplasmic reticulum (EnR) stress that is often induced in the tumor microenvironment because of inadequate vascularization. Previous studies report an association between activation of the UPR and reduced sensitivity to antiestrogens and chemotherapeutics in estrogen receptor α (ERα)- positive and triple-negative breast cancers, respectively. ERα has been shown to regulate the expression of a key mediator of the EnR stress response, the X-box-binding protein-1 (XBP-1). Although network prediction models have associated ERβ with the EnR stress response, its role as regulator of the UPR has not been experimentally tested. Here, upregulation of wild-type ERβ (ERβ1) or treatment with ERβ agonists enhanced apoptosis in breast cancer cells in the presence of pharmacological inducers of EnR stress. Targeting the BCL-2 to the EnR of the ERβ1-expressing cells prevented the apoptosis induced by EnR stress but not by non-EnR stress apoptotic stimuli indicating that ERβ1 promotes EnR stress-regulated apoptosis. Downregulation of inositol-requiring kinase 1α (IRE1α) and decreased splicing of XBP-1 were associated with the decreased survival of the EnR-stressed ERβ1-expressing cells. ERβ1 was found to repress the IRE1 pathway of the UPR by inducing degradation of IRE1α.
    [Show full text]
  • Targeting Estrogen Receptor Subtypes (Era and Erb) with Selective ER Modulators in Ovarian Cancer
    KK-L CHAN and others Estrogen receptor subtypes in 221:2 325–336 Research ovarian cancer Targeting estrogen receptor subtypes (ERa and ERb) with selective ER modulators in ovarian cancer Karen Kar-Loen Chan, Thomas Ho-Yin Leung, David Wai Chan, Na Wei, Correspondence Grace Tak-Yi Lau, Stephanie Si Liu, Michelle K-Y Siu and Hextan Yuen-Sheung Ngan should be addressed to K K-L Chan Department of Obstetrics and Gynaecology, LKS Faculty of Medicine, The University of Hong Kong, Email 6/F Professorial Block, Queen Mary Hospital, Pokfulam, Hong Kong [email protected] Abstract Ovarian cancer cells express both estrogen receptor a (ERa) and ERb, and hormonal therapy is Key Words an attractive treatment option because of its relatively few side effects. However, estrogen " estrogen receptors was previously shown to have opposite effects in tumors expressing ERa compared with ERb, " SERMS indicating that the two receptor subtypes may have opposing effects. This may explain the " ovarian cancer modest response to nonselective estrogen inhibition in clinical practice. In this study, we " hormonal treatment aimed to investigate the effect of selectively targeting each ER subtype on ovarian cancer growth. Ovarian cancer cell lines SKOV3 and OV2008, expressing both ER subtypes, were treated with highly selective ER modulators. Sodium 30-(1-(phenylaminocarbonyl)-3,4- Journal of Endocrinology tetrazolium)-bis(4-methoxy-6-nitro) benzene sulfonic acid hydrate (XTT) assay revealed that treatment with 1,3-bis(4-hydroxyphenyl)-4-methyl-5-[4-(2-piperidinylethoxy)phenol]-1H- pyrazole dihydrochloride (MPP) (ERa antagonist) or 2,3-bis(4-hydroxy-phenyl)-propionitrile (DPN) (ERb agonist) significantly suppressed cell growth in both cell lines.
    [Show full text]
  • In Silico Prediction of Heliannuol A, B, C, D, and E Compounds on Estrogen Receptor Β Agonists
    Indonesian Journal of Cancer Chemoprevention, February 2021 ISSN: 2088–0197 e-ISSN: 2355-8989 In Silico Prediction of Heliannuol A, B, C, D, and E Compounds on Estrogen Receptor β Agonists Roihatul Mutiah, Alif Firman Firdausy, Yen Yen Ari Indrawijaya, Hibbatullah* Department of Pharmacy, Faculty of Medical and Health Sciences, Maulana Malik Ibrahim State Islamic University of Malang, Indonesia Abstract Heliannuols has a benzoxepine ring that produces anticancer activity by the inhibition mechanism of phosphoinositide 3 kinases (PI3K). Heliannuols are a compound that can be found in the leaves of sunflower Helianthus( annuus L.). The purpose of this study is to predict interactions, toxicity, physicochemical, and pharmacokinetics of Heliannuol A, B, C, D, and E based in silico as candidate anticancer drugs. Estrogen receptor beta (ERβ) is a new potential therapy for glioma with an antiproliferative effect. Ligands agonist ERβ have the potential activity to inhibit the proliferation of glioma cells and the discovery of this ligand has opened new therapy through the ERβ to prolong survival in cancer patients. Prediction of physicochemical properties based on Lipinski rules and penetrate in the blood-brain barrier. Receptor validation shows that 2I0G(A) has a smaller RMSD value than 2I0G(B), receptor validation is valid if the RMSD value less than 2. The result of molecular docking shows that Heliannuols comply with Lipinski rules and have low toxicity. Heliannuols also have a similar amino acid with comparison drug (Erteberel), but the rerank score of Erteberel still lower than Heliannuols. Keywords: Helianthus annuus, Heliannuols, estrogen receptor β (ERβ), in silico, toxicity. INTRODUCTION using HPLC with hexane and ethyl acetate solvents (Macias, et al., 1994; Macias, et al., 2000; Macias, Sunflower plant (Helianthus annuus L.) has et al., 2002).
    [Show full text]
  • G Protein-Coupled Estrogen Receptor in Cancer and Stromal Cells: Functions and Novel Therapeutic Perspectives
    cells Review G Protein-Coupled Estrogen Receptor in Cancer and Stromal Cells: Functions and Novel Therapeutic Perspectives Richard A. Pepermans 1, Geetanjali Sharma 1,2 and Eric R. Prossnitz 1,2,3,* 1 Division of Molecular Medicine, Department of Internal Medicine, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA; [email protected] (R.A.P.); [email protected] (G.S.) 2 Center of Biomedical Research Excellence in Autophagy, Inflammation and Metabolism, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA 3 University of New Mexico Comprehensive Cancer Center, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA * Correspondence: [email protected]; Tel.: +1-505-272-5647 Abstract: Estrogen is involved in numerous physiological and pathophysiological systems. Its role in driving estrogen receptor-expressing breast cancers is well established, but it also has important roles in a number of other cancers, acting both on tumor cells directly as well as in the function of multiple cells of the tumor microenvironment, including fibroblasts, immune cells, and adipocytes, which can greatly impact carcinogenesis. One of its receptors, the G protein-coupled estrogen receptor (GPER), has gained much interest over the last decade in both health and disease. Increasing evidence shows that GPER contributes to clinically observed endocrine therapy resistance in breast cancer while also playing a complex role in a number of other cancers. Recent discoveries regarding the targeting of GPER in combination with immune checkpoint inhibition, particularly in melanoma, have led to the initiation of the first Phase I clinical trial for the GPER-selective agonist G-1.
    [Show full text]
  • Design and Synthesis of Selective Estrogen Receptor Β Agonists and Their Hp Armacology K
    Marquette University e-Publications@Marquette Dissertations (2009 -) Dissertations, Theses, and Professional Projects Design and Synthesis of Selective Estrogen Receptor β Agonists and Their hP armacology K. L. Iresha Sampathi Perera Marquette University Recommended Citation Perera, K. L. Iresha Sampathi, "Design and Synthesis of Selective Estrogen Receptor β Agonists and Their hP armacology" (2017). Dissertations (2009 -). 735. https://epublications.marquette.edu/dissertations_mu/735 DESIGN AND SYNTHESIS OF SELECTIVE ESTROGEN RECEPTOR β AGONISTS AND THEIR PHARMACOLOGY by K. L. Iresha Sampathi Perera, B.Sc. (Hons), M.Sc. A Dissertation Submitted to the Faculty of the Graduate School, Marquette University, in Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy Milwaukee, Wisconsin August 2017 ABSTRACT DESIGN AND SYNTHESIS OF SELECTIVE ESTROGEN RECEPTOR β AGONISTS AND THEIR PHARMACOLOGY K. L. Iresha Sampathi Perera, B.Sc. (Hons), M.Sc. Marquette University, 2017 Estrogens (17β-estradiol, E2) have garnered considerable attention in influencing cognitive process in relation to phases of the menstrual cycle, aging and menopausal symptoms. However, hormone replacement therapy can have deleterious effects leading to breast and endometrial cancer, predominantly mediated by estrogen receptor-alpha (ERα) the major isoform present in the mammary gland and uterus. Further evidence supports a dominant role of estrogen receptor-beta (ERβ) for improved cognitive effects such as enhanced hippocampal signaling and memory consolidation via estrogen activated signaling cascades. Creation of the ERβ selective ligands is challenging due to high structural similarity of both receptors. Thus far, several ERβ selective agonists have been developed, however, none of these have made it to clinical use due to their lower selectivity or considerable side effects.
    [Show full text]
  • Helianthus Annuus L.) TERHADAP RESEPTOR ESTROGEN Β (Erβ) (2I0G
    STUDI IN SILICO SENYAWA Heliannuol A, B, C, D, dan E PADA TANAMAN BUNGA MATAHARI (Helianthus annuus L.) TERHADAP RESEPTOR ESTROGEN β (ERβ) (2I0G) SKRIPSI Oleh: HIBBATULLAH NIM. 16670036 PROGRAM STUDI FARMASI FAKULTAS KEDOKTERAN DAN ILMU KESEHATAN UNIVERSITAS ISLAM NEGERI MAULANA MALIK IBRAHIM MALANG 2020 STUDI IN SILICO SENYAWA Heliannuol A, B, C, D, dan E PADA TANAMAN BUNGA MATAHARI (Helianthus annuus L.) TERHADAP RESEPTOR ESTROGEN β (ERβ) (2I0G) SKRIPSI Diajukan Kepada: Fakultas Kedokteran dan Ilmu Kesehatan Universitas Islam Negeri (UIN) Maulana Malik Ibrahim Malang Untuk Memenuhi Salah Satu Persyaratan Memperoleh Gelar Sarjana Farmasi (S.Farm) PROGRAM STUDI FARMASI FAKULTAS KEDOKTERAN DAN ILMU KESEHATAN UNIVERSITAS ISLAM NEGERI MAULANA MALIK IBRAHIM MALANG 2020 STUDI IN SILICO SENYAWA Heliannuol A, B, C, D, dan E PADA TANAMAN BUNGA MATAHARI (Helianthus annuus L.) TERHADAP RESEPTOR ESTROGEN β (ERβ) (2I0G) SKRIPSI Oleh: HIBBATULLAH NIM. 16670036 Telah Diperiksa dan Disetujui untuk Diuji: Tanggal: 19 Mei 2020 Pembimbing I Pembimbing II Dr. apt. Roihatul Muti’ah, M.Kes. apt. Alif Firman F., S.Farm., M.Biomed. NIP. 19800203 200912 2 003 NIP. 19920607 201903 1 017 Mengetahui, Ketua Program studi Farmasi apt. Abdul Hakim, M.P.I. M.Farm. NIP. 19761214 200912 1 002 STUDI IN SILICO SENYAWA Heliannuol A, B, C, D, dan E PADA TANAMAN BUNGA MATAHARI (Helianthus annuus L.) TERHADAP RESEPTOR ESTROGEN β (ERβ) (2I0G) SKRIPSI Oleh: HIBBATULLAH NIM. 16670036 Telah Dipertahankan di Depan Dewan Penguji Skripsi Dan Dinyatakan Diterima Sebagai Salah Satu Persyaratan Untuk Mendapatkan Gelar Sarjani Farmasi (S.Farm) Tanggal: 19 Mei 2020 Ketua Penguji : apt. Yen Yen Ari I., M.Farm.Klin.
    [Show full text]
  • Estradiol Selectively Stimulates Endothelial Prostacyclin Production Through Estrogen Receptor-A
    237 Estradiol selectively stimulates endothelial prostacyclin production through estrogen receptor-a Agua Sobrino1, Pilar J Oviedo1,2, Susana Novella1,3, Andre´s Laguna-Fernandez1, Carlos Bueno1,3, Miguel Angel Garcı´a-Pe´rez1, Juan J Tarı´n4, Antonio Cano5 and Carlos Hermenegildo3 1Research Foundation, and 2Cardiology Service, Hospital Clı´nico Universitario, Avenida Blasco Iban˜ez, 17, E 46010 Valencia, Spain 3Departments of Physiology, 4Functional Biology and Physical Anthropology and 5Pediatrics, Obstetrics and Gynaecology, University of Valencia, Avenida Blasco Iban˜ez, 15, E 46010 Valencia, Spain (Correspondence should be addressed to C Hermenegildo; Email: [email protected]) Abstract Estradiol (E2) acts on the endothelium to promote vasodilatation through the release of several compounds, including prostanoids, which are products of arachidonic acid metabolism. Among these, prostacyclin (PGI2) and thromboxane A2 (TXA2) exert opposite effects on vascular tone. The role of different estrogen receptors (ERs) in the PGI2/TXA2 balance, however, has not been fully elucidated. Our study sought to uncover whether E2 enhances basal production of PGI2 or TXA2 in cultured human umbilical vein endothelial cells (HUVECs), to analyze the enzymatic mechanisms involved, and to evaluate the different roles of both types of ERs (ERa and ERb). HUVECs were exposed to E2, selective ERa (1,3,5- tris(4-hydroxyphenyl)-4-propyl-1h-pyrazole, PPT) or ERb (diarylpropionitrile, DPN) agonists and antagonists (unspecific: ICI 182 780; specific for ERa: methyl-piperidino-pyrazole, MPP). PGI2 and TXA2 production was measured by ELISA. Expression of phospholipases, cyclooxygenases (COX-1 and COX-2), PGI2 synthase (PGIS), and thromboxane synthase (TXAS) was analyzed by western blot and quantitative RT-PCR.
    [Show full text]
  • The Effect of Intrahippocampal Injection of Diarylpropionitrile, a Selective Estrogen Receptor-Beta Agonist, on Passive Avoidanc
    Physiology and Pharmacology, 12 (4), 254 - 260 Winter 2009 [Article in Persian] The effect of intrahippocampal injection of diarylpropionitrile, a selective estrogen receptor-β agonist, on passive avoidance learning Zeinab Sharifkhodaei 1,2, Nasser Naghdi 2*, Shahrbanoo Oryan 3, Parichehr Yaghmaei 1 1. Dept. Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran 2. Dept. Physiology and Pharmacology, Pasteur Institute of Iran, Tehran, Iran 3. Dept. Biology, Tarbiat Moalem University, Tehran, Iran Received: 5 Mar 2008 Revised: 23 Aug 2008 Accepted: 25 Aug 2008 Abstract* Introduction: Neurohormones like testosterone and estradiol have an important role in learning and memory. The hippocampus is essentially involved in learning and memory, and is known to be a target for estradiol actions. Estrogen receptors (ERs) are highly expressed in CA1 of rat hippocampus, and mediate the effects of estrogen on learning and memory. Estradiol receptor belong to a family of transcription factors, the nuclear receptor superfamily, and has two subtypes ERα and ERβ. The current research has been conducted to assess the effect of ERβ selective agonist, diarylpropionitrile (DPN), on passive avoidance of adult male rats, by using passive avoidance task. Methods: Male adult rats were bilaterally cannulated into the CA1 area of hippocampus, and then received vehicle (dimethyl sulfoxide, DMSO) or DPN (0.2, 0.5, 1 µg/0.5µl/side), 30 min before training on passive avoidance task. Results: The results showed that pre-training intra-CA1 injections of DPN (0.5, 1 µg/0.5µl/side), significantly decreased step-through latencies and increased time spent in dark on passive avoidance learning (P<0.01).
    [Show full text]