INRS - Centre Armand-Frappier Santé Biotechnologie, Laval, QC, H7V 1B7, Canada.
INRS - Centre Armand-Frappier Santé Biotechnologie, Laval, QC, H7V 1B7, Canada.
Mol Cell Endocrinol. 2019 Dec 1;498:110583. doi: 10.1016/j.mce.2019.110583. Epub 2019 Sep 16.
In this study, we determined whether estragole and its isomer trans-anethole interfered with feto-placental steroidogenesis in a human co-culture model composed of fetal-like adrenocortical (H295R) and placental trophoblast-like (BeWo) cells. Estragole and trans-anethole are considered the biologically active compounds within basil and fennel seed essential oils, respectively. After a 24 h exposure of the co-culture to 2.5, 5.2 and 25 μM estragole or trans-anethole, hormone concentrations of estradiol, estrone, dehydroepiandrosterone, androstenedione, progesterone and estriol were significantly increased. Using RT-qPCR, estragole and trans-anethole were shown to significantly alter the expression of several key steroidogenic enzymes, such as those involved in cholesterol transport and steroid hormone biosynthesis, including StAR, CYP11A1, HSD3B1/2, SULT2A1, and HSD17B1, -4, and -5. Furthermore, we provided mechanistic insight into the ability of estragole and trans-anethole to stimulate promoter-specific expression of CYP19 through activation of the PKA pathway in H295R cells and the PKC pathway in BeWo cells, in both cases associated with increased cAMP levels. Moreover, we show new evidence suggesting a role for progesterone in regulating steroid hormone biosynthesis through regulation of the StAR gene.
在这项研究中，我们确定了芫荽烯及其异构体反式茴香脑是否会干扰由胎儿样肾上腺皮质（H295R）和胎盘滋养层样（BeWo）细胞组成的人共培养模型中的胎-胎盘类固醇生成。芫荽烯和反式茴香脑分别被认为是罗勒和茴香籽精油中的生物活性化合物。在将共培养物暴露于 2.5、5.2 和 25 μM 芫荽烯或反式茴香脑 24 小时后，雌二醇、雌酮、脱氢表雄酮、雄烯二酮、孕酮和雌三醇的激素浓度显著增加。通过 RT-qPCR，芫荽烯和反式茴香脑显示出显著改变几种关键类固醇生成酶的表达，例如参与胆固醇转运和类固醇激素生物合成的酶，包括 StAR、CYP11A1、HSD3B1/2、SULT2A1 和 HSD17B1、-4 和 -5。此外，我们提供了机制见解，表明芫荽烯和反式茴香脑能够通过激活 H295R 细胞中的 PKA 途径和 BeWo 细胞中的 PKC 途径，刺激 CYP19 的启动子特异性表达，从而刺激 H295R 细胞和 BeWo 细胞中的 PKA 途径和 PKC 途径，在这两种情况下都与 cAMP 水平的增加有关。此外，我们还提供了新的证据表明，孕酮通过调节 StAR 基因在调节类固醇激素生物合成中发挥作用。
