Anatomy and Cell Biology, University of Munich, Munich, Germany.
Endocrinology. 2012 Mar;153(3):1472-83. doi: 10.1210/en.2011-1769. Epub 2012 Jan 10.
The neurotransmitter norepinephrine (NE) is derived from the sympathetic nervous system and may be involved in the regulation of ovarian functions. Ovarian innervation increases in patients with polycystic ovarian syndrome (PCOS), prompting us to readdress a role of NE in the human ovary. In vitro fertilization-derived granulosa cells (GC), follicular fluids (FF), and ovarian sections were studied. NE was found in FF and freshly isolated GC, yet significantly lower levels of NE were detected in samples from PCOS patients. Furthermore, the metabolite normetanephrine was detected in FF. Together this suggests cellular uptake and metabolism of NE in GC. In accordance, the NE transporter and NE-metabolizing enzymes [catechol-o-methyltransferase (COMT) and monoamine oxidase A] were found in GC, COMT in GC and thecal cells of large human antral follicles in vivo and in cultured GC. Cellular uptake and metabolism of NE also occurred in cultured GC, events that could be blocked pharmacologically. NE, in the range present in FF, is unlikely to affect GC via activation of typical α- or β-receptors. In line with this assumption, it did not alter phosphorylation of MAPK. However, NE robustly induced the generation of reactive oxygen species (ROS). This action occurred even when receptors were blocked but was prevented by blockers of NE transporter, COMT, and monoamine oxidase A. Thus, NE contributes to the microenvironment of preovulatory human follicles and is lower in PCOS. By inducing the production of ROS in GC, NE is linked to ROS-regulated events, which are emerging as crucial factors in ovarian physiology, including ovulation.
神经递质去甲肾上腺素（NE）来源于交感神经系统，可能参与调节卵巢功能。多囊卵巢综合征（PCOS）患者的卵巢神经支配增加，这促使我们重新研究 NE 在人卵巢中的作用。我们研究了体外受精衍生的颗粒细胞（GC）、卵泡液（FF）和卵巢切片。在 FF 和新分离的 GC 中发现了 NE，但在 PCOS 患者的样本中检测到的 NE 水平明显较低。此外，还在 FF 中检测到代谢产物去甲变肾上腺素。这表明 NE 在 GC 中被摄取和代谢。因此，在 GC 中发现了 NE 转运体和 NE 代谢酶[儿茶酚-O-甲基转移酶（COMT）和单胺氧化酶 A]，COMT 在 GC 和体内大卵泡的卵巢膜细胞以及培养的 GC 中均有发现。NE 的摄取和代谢也发生在培养的 GC 中，这些事件可以通过药理学阻断。在 FF 中存在的范围内，NE 不太可能通过激活典型的α或β受体影响 GC。这种假设与它不会改变 MAPK 的磷酸化一致。然而，NE 强烈诱导活性氧（ROS）的产生。即使受体被阻断，这种作用仍会发生，但 NE 转运体、COMT 和单胺氧化酶 A 的抑制剂可阻止这种作用。因此，NE 有助于人类排卵前卵泡的微环境，并且在 PCOS 中含量较低。通过诱导 GC 中 ROS 的产生，NE 与 ROS 调节的事件有关，这些事件正在成为卵巢生理学中至关重要的因素，包括排卵。
