Department of Physiology, St Marianna University School of Medicine, Miyamae-ku, Kawasaki, Japan.
J Neuroendocrinol. 2009 Dec;21(12):1029-37. doi: 10.1111/j.1365-2826.2009.01928.x. Epub 2009 Oct 20.
Prostaglandins (PGs), especially PGE(2), are involved in the hypothalamic control of gonadotrophin-releasing hormone (GnRH) release, acting at least in part on the terminal of GnRH axons in the median eminence. The present study aimed: (i) to clarify the role of PG(s) in regulating GnRH cell function at the level of the perikarya in the preoptic area; (ii) to determine the cyclooxygenase (COX) isozyme responsible for producing PG(s) that regulates GnRH perikarya; and (iii) to identify cell types that contain the responsible COX isozyme in female rats. A surge of luteinising hormone (LH) secretion was induced by oestrogen and progesterone in ovariectomised rats. Treatment of the rat before the LH surge with indomethacin, a nonselective COX inhibitor, or NS-398, a selective COX-2 inhibitor, did not interfere with the surge. However, treatment with indomethacin or flurbiprofen, a selective COX-1 inhibitor, significantly reduced the number of GnRH-immunoreactive cells in the preoptic area at the time of peak LH secretion during the surge. NS-398 did not affect the GnRH immunoreactivity. Double-labelled immunofluorescent histochemistry revealed COX-1 immunoreactivity in the vicinity of, but not within, GnRH containing neurones in the preoptic area. COX-2 immunoreactivity was not found in the same area. The COX-1 immunoreactivity was almost entirely localised in microglia in the preoptic area, but not in neurones or astrocytes. These results suggest that microglia in the preoptic area containing COX-1 are responsible for producing PG(s), which, in turn, facilitates the accumulation of GnRH during the gonadotrophin surge in female rats.
前列腺素（PGs），特别是 PGE（2），参与了促性腺激素释放激素（GnRH）释放的下丘脑控制，至少部分作用于正中隆起处 GnRH 轴突的末端。本研究旨在：（i）阐明 PG（s）在调节视前区 GnRH 细胞功能方面的作用；（ii）确定负责产生调节 GnRH 胞体的 PG（s）的环氧化酶（COX）同工酶；（iii）确定在雌性大鼠中含有负责的 COX 同工酶的细胞类型。在去卵巢大鼠中，雌激素和孕激素诱导黄体生成素（LH）分泌激增。在 LH 激增前用非选择性 COX 抑制剂吲哚美辛或选择性 COX-2 抑制剂 NS-398 处理大鼠，不会干扰激增。然而，用吲哚美辛或氟比洛芬（一种选择性 COX-1 抑制剂）处理，会显著减少 LH 激增期间 GnRH 免疫反应细胞的数量。NS-398 不会影响 GnRH 免疫反应。双重免疫荧光组织化学显示 COX-1 免疫反应位于视前区 GnRH 含神经元的附近，但不在其内。在同一区域未发现 COX-2 免疫反应。COX-1 免疫反应几乎完全局限于视前区的小胶质细胞中，而不是神经元或星形胶质细胞中。这些结果表明，视前区含有 COX-1 的小胶质细胞负责产生 PG（s），这反过来又促进了 GnRH 在雌性大鼠促性腺激素激增期间的积累。
