NICOTINE, COTININE, AND ANABASINE INHIBIT AROMATASE IN HUMAN TROPHOBLAST INVITRO
NICOTINE, COTININE, AND ANABASINE INHIBIT AROMATASE IN HUMAN TROPHOBLAST INVITRO
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DOI：
10.1172/jci112494
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发表时间：
1986-06-01
影响因子：
15.9
通讯作者：
RYAN, KJ
中科院分区：
文献类型：
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作者：
BARBIERI, RL;GOCHBERG, J;RYAN, KJ
流行病学研究表明，吸烟的女性比不吸烟的女性内源性雌激素水平低。为了探讨吸烟和内源性雌激素减少之间的可能联系，我们研究了烟草成分对人绒毛膜癌细胞和足月胎盘微粒体雌激素产生的影响。在绒毛膜癌细胞培养物中，尼古丁、可替宁（尼古丁的主要代谢物）和假木贼碱（香烟烟草的次要成分）均以剂量依赖性方式抑制雄烯二酮转化为雌激素。从培养基中去除尼古丁、可替宁和假木贼碱导致芳香酶抑制的完全逆转。在绒毛膜癌细胞培养物中，培养基中超生理浓度的雄烯二酮（73 μ M）阻断由尼古丁、可替宁、假木贼碱引起的芳香酶抑制。在准备长期胎盘微粒体，尼古丁，可替宁，和假木贼碱抑制睾酮转化为雌激素。动力学分析表明，相对于底物的抑制是竞争性的。这些结果表明，一些烟碱生物碱直接抑制芳香化酶。这种机制可以部分解释吸烟女性体内雌激素的减少。
Epidemiologic studies suggest that women who smoke have lower endogenous estrogen than nonsmokers. To explore the possible link between cigarette smoking and decreased endogenous estrogens, we have examined the effects of constituents of tobacco on estrogen production in human choriocarcinoma cells and term placental microsomes. In choriocarcinoma cell cultures, nicotine, cotinine (a major metabolite of nicotine), and anabasine (a minor component of cigarette tobacco) all inhibited androstenedione conversion to estrogen in a dose-dependent fashion. Removal of nicotine, cotinine, and anabasine from the culture medium resulted in the complete reversal of the inhibition of aromatase. In the choriocarcinoma cell cultures, a supraphysiologic concentration of androstenedione (73 .mu.M) in the culture medium blocked the inhibition of aromatase caused by nicotine, cotinine, anabasine. In preparations of term placental microsomes, nicotine, cotinine, and anabasine inhibited the conversion of testosterone to estrogen. Kinetic analysis demonstrated the inhibition to be competitive with respect to the substrate. These findings suggest that some nicotinic alkaloids directly inhibit aromatase. This mechanism may explain, in part, the decreased estrogen observed in women who smoke.