Oxygen-Sensitive K+ Channels Modulate Human Chorionic Gonadotropin Secretion from Human Placental Trophoblast.
Oxygen-Sensitive K+ Channels Modulate Human Chorionic Gonadotropin Secretion from Human Placental Trophoblast.
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DOI：
10.1371/journal.pone.0149021
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Greenwood SL
中科院分区：
文献类型：
--
作者：
Díaz P;Sibley CP;Greenwood SL
人绒毛膜促性腺激素（hCG）是胎盘合体滋养层（胎盘的运输上皮）的关键自分泌/旁分泌调节剂。合胞体滋养层hCG分泌受氧分压（pO 2）、活性氧（ROS）和钾（K+）通道调节。在这里，我们测试的假设，K+通道介导的pO 2和ROS对hCG分泌的影响。将来自正常足月妊娠的胎盘绒毛外植体在6%（常氧）、21%（高氧）或1%（缺氧）pO 2下培养6天。在第3-5天，用5 mM 4-氨基吡啶（4-AP）或四乙基铵（TEA）、pO 2敏感性电压门控K+（KV）通道阻断剂或ROS（10-1000μM H2 O2）处理外植体。每天测定hCG分泌和乳酸脱氢酶（LDH）释放（坏死标志物）。在第6天，在组织裂解物中测量hCG和LDH，并评估86 Rb（K+）流出以估计合体滋养层K+渗透性。hCG分泌和86 Rb流出显着更大的外植体维持在21%pO2比常氧。4-AP/TEA在21% pO 2时对hCG分泌的抑制程度大于6%和1%pO2，在21% pO 2时减少86 Rb流出，但在6%pO2时不减少。LDH释放和组织LDH/hCG在6%、21%和1%pO2下相似，并且不受4-AP/TEA的影响。H2 O2刺激86 Rb流出和hCG分泌在常氧，但减少86 Rb流出，而不影响hCG分泌，在21%pO2。4-AP/TEA敏感性K+通道参与合体滋养细胞pO 2敏感性hCG分泌ROS对hCG分泌和86 Rb外排的影响都是pO 2依赖性的，但两者之间的因果关系仍有待建立。
Human chorionic gonadotropin (hCG) is a key autocrine/paracrine regulator of placental syncytiotrophoblast, the transport epithelium of the human placenta. Syncytiotrophoblast hCG secretion is modulated by the partial pressure of oxygen (pO2), reactive oxygen species (ROS) and potassium (K+) channels. Here we test the hypothesis that K+ channels mediate the effects of pO2 and ROS on hCG secretion. Placental villous explants from normal term pregnancies were cultured for 6 days at 6% (normoxia), 21% (hyperoxia) or 1% (hypoxia) pO2. On days 3–5, explants were treated with 5mM 4-aminopyridine (4-AP) or tetraethylammonium (TEA), blockers of pO2-sensitive voltage-gated K+ (KV) channels, or ROS (10–1000μM H2O2). hCG secretion and lactate dehydrogenase (LDH) release, a marker of necrosis, were determined daily. At day 6, hCG and LDH were measured in tissue lysate and 86Rb (K+) efflux assessed to estimate syncytiotrophoblast K+ permeability. hCG secretion and 86Rb efflux were significantly greater in explants maintained in 21% pO2 than normoxia. 4-AP/TEA inhibited hCG secretion to a greater extent at 21% than 6% and 1% pO2, and reduced 86Rb efflux at 21% but not 6% pO2. LDH release and tissue LDH/hCG were similar in 6%, 21% and 1% pO2 and unaffected by 4-AP/TEA. H2O2 stimulated 86Rb efflux and hCG secretion at normoxia but decreased 86Rb efflux, without affecting hCG secretion, at 21% pO2. 4-AP/TEA-sensitive K+ channels participate in pO2-sensitive hCG secretion from syncytiotrophoblast. ROS effects on both hCG secretion and 86Rb efflux are pO2-dependent but causal links between the two remain to be established.