Shi C Z, Zhuang L Z
State Key Laboratory of Reproductive Biology, Chinese Academy of Sciences, Beijing.
Placenta. 1993 Nov-Dec;14(6):683-93. doi: 10.1016/s0143-4004(05)80385-6.
The effect of norepinephrine (NE) upon human chorionic gonadotrophin (hCG) production by 6-8 week gestation placental explants has been investigated. NE (5 micrograms/ml) enhanced hCG secretion significantly from the second day of treatment. The stimulatory effect of NE on hCG secretion could be abolished by the alpha 1-receptor specific antagonist prazosin (10(-4) M) and partly diminished by the beta 1-receptor specific antagonist atenolol (10(-4) M), but was not influenced by the alpha 2-receptor specific antagonist yohimbine (10(-4) M). The involvement of the alpha-receptor in the regulation of hCG secretion was further confirmed by addition of the alpha-receptor agonist clonidine (10(-6) M) which had a similar stimulatory effect on hCG release but the effect was antagonized by both prazosin and yohimbine. Further study showed that NE induced a significant increase in cyclic adenosine monophosphate (cAMP) production by trophoblast tissue. Cyclic AMP secretion in the NE-treated group was fivefold higher than that of the control group. Both the protein kinase C (PKC) specific activator 1-deoyl-2-acetyl-sn-glycerol (OAG) and the PKC non-specific activator phorbol-12-myristate-13-acetate (PMA) had a stimulatory effect on hCG secretion, while the PKC inhibitor, 1-(5-isoquinolinylsulfonyl)-2-methyl-piperazine (H7) diminished the hCG secretion stimulated by NE. The effect of NE was blocked by the voltage-dependent calcium channel blocker nifedipine but not by the voltage-independent calcium channel blocker gadolinium chloride (GdCl3). On the other hand, anti-gonadotrophin releasing hormone (GnRH) IgG and the GnRH antagonist (D-Phe2, D-Trp6)-GnRH did not influence the stimulatory effect of NE on hCG release. The results indicate that NE regulates hCG production in human first trimester trophoblast tissue. The effect of NE was mainly mediated by alpha 1 and partly by beta 1 receptors. Cyclic AMP, the PKC signal transduction pathway and the voltage-dependent calcium channels were involved in NE action.
研究了去甲肾上腺素（NE）对妊娠6 - 8周胎盘外植体产生人绒毛膜促性腺激素（hCG）的影响。从治疗第二天起，NE（5微克/毫升）显著增强了hCG的分泌。NE对hCG分泌的刺激作用可被α1受体特异性拮抗剂哌唑嗪（10⁻⁴ M）消除，部分被β1受体特异性拮抗剂阿替洛尔（10⁻⁴ M）减弱，但不受α2受体特异性拮抗剂育亨宾（10⁻⁴ M）影响。添加α受体激动剂可乐定（10⁻⁶ M）对hCG释放有类似的刺激作用，但该作用被哌唑嗪和育亨宾拮抗，进一步证实了α受体参与hCG分泌的调节。进一步研究表明，NE诱导滋养层组织中环磷酸腺苷（cAMP）产生显著增加。NE处理组的cAMP分泌比对照组高五倍。蛋白激酶C（PKC）特异性激活剂1 - 脱氧 - 2 - 乙酰 - sn - 甘油（OAG）和PKC非特异性激活剂佛波醇 - 12 - 肉豆蔻酸酯 - 13 - 乙酸酯（PMA）对hCG分泌均有刺激作用，而PKC抑制剂1 -（5 - 异喹啉磺酰基）- 2 - 甲基 - 哌嗪（H7）则减弱了NE刺激的hCG分泌。NE的作用被电压依赖性钙通道阻滞剂硝苯地平阻断，但不被电压非依赖性钙通道阻滞剂氯化钆（GdCl₃）阻断。另一方面，抗促性腺激素释放激素（GnRH）IgG和GnRH拮抗剂（D - Phe²，D - Trp⁶）- GnRH不影响NE对hCG释放的刺激作用。结果表明，NE调节人孕早期滋养层组织中hCG的产生。NE的作用主要由α1受体介导，部分由β1受体介导。cAMP、PKC信号转导途径和电压依赖性钙通道参与了NE的作用。
