REGULATION OF WATER CHANNEL GENE(AQP-CHIP) EXPRESSION BY ESTRADIOL AND ANORDIOL IN RAT UTERUS

本研究观察了雌二醇和Ａｎｏｒｄｉｏｌ（一种有激动剂活性的抗雌激素药物）对未成年雌性大鼠子宫水通道（ＡＱＰＣＨＩＰ）基因表达的调控作用。我们根据两种大鼠ＡＱＰＣＨＩＰ水通道ｃＤＮＡ保守序列设计合成了一对寡核苷酸引物，用于扩增从大鼠子宫总ＲＮＡ反转录而成的ｃＤＮＡ片段。给未成年大鼠用单剂量的雌二醇（４０μｇ·ｋｇ－１）９ｈ后，ＡＱＰＣＨＩＰｍＲＮＡ的表达量显著增加。雌二醇和Ａｎｏｒｄｉｏｌ的最低有效量分别为４０μｇ·ｋｇ－１和５０μｇ·ｋｇ－１，但Ａｎｏｒｄｉｏｌ的刺激作用比雌二醇强。本文结果提示，ＡＱＰＣＨＩＰ水通道基因的表达可能与雌二醇和Ａｎｏｒｄｉｏｌ介导的子宫水的浸渗作用以及子宫腔内液体的产生有关     

双炔失碳酯类似物的合成

为寻找抗早孕有效的避孕药，合成了五个未见文献报道的双炔失碳酯类似物，本文报道了它们的合成方法及元素分析、质谱、红外，核磁共振等光谱数据，小白鼠初步药理试验表明化合物Ⅵ、Ⅷ、Ⅳ具有较好的抗早孕活性。     

Predominant contributions of carboxylesterase 1 and 2 in hydrolysis of anordrin in humans

1.?Anordrin (2α, 17α-diethynyl-A-nor-5α-androstane-2β, 17β-diol diproprionate) is post-coital contraceptive drug that is on the market in China for more than 30 years. This study aims to elucidate enzymes involved in anordrin hydrolysis, and to evaluate the significant role of carboxylesterases in anordrin hydrolysis in humans.

2.?Human liver and intestinal microsomes, recombinant human carboxylesterase were selected as enzyme sources. In human liver microsomes, intrinsic clearance was 684?±?83?μL/min/mg protein, which was considerably higher than the value of intestine microsomes (94.6?±?13.3?μL/min/mg protein). Carboxylesterase (CES) 1 has more contribution than CES2 in human liver.

3.?Inhibition studies were performed using representative esterase inhibitors to confirm esterase isoforms involved in anordrin hydrolysis. Simvastatin strongly inhibited hydrolytic process of anordrin in liver and intestine microsomes, with IC₅₀ values of 10.9?±?0.1 and 6.94?±?0.03?μM, respectively.

4.?The present study investigated for the first time hydrolytic enzyme phenotypes of anordrin. Anordrin is predominantly catalyzed by CES1 and CES2 to generate the main active metabolite, anordiol. Moreover, anordrin and its metabolite anordiol can be altered by esterase inhibitors, such as simvastatin, upon exposure in vivo.