Kugu K, Dharmarajan A M, Preutthipan S, Wallach E E
Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
J Reprod Fertil. 1995 Mar;103(2):273-8. doi: 10.1530/jrf.0.1030273.
The objectives of these experiments were to determine (i) the role of calcium/calmodulin-dependent protein kinase II-mediated signal transduction in hCG-induced ovulation and (ii) whether there is an association between arachidonic acid metabolites, nitric oxide and calcium/calmodulin-dependent protein kinase II in the overall scheme of ovulation induction. Ovarian arteries were cannulated in situ, and the ovaries were excised and perfused in vitro. Ovulatory efficiency ([number of ovulated follicles/number of mature follicles > 1.5 mm] x 100) was calculated for each experiment. Calcium/calmodulin-dependent protein kinase II substrate induced ovulation in the absence of gonadotrophin (calcium/calmodulin-dependent protein kinase II substrate: 66.3%; control: 0%). In the next experiment, perfusion medium of the experimental ovary was supplemented with KN 62, a potent inhibitor of calcium/calmodulin-dependent protein kinase II, while the contralateral ovary served as control. Ovulations were induced in both ovaries with hCG (50 iu (150 ml)-1) and perfusion was continued for 8 h. In the third experiment, ovaries were perfused with prostaglandin F2 alpha (PGF2 alpha) with and without KN 62, while the contralateral ovary was perfused with medium alone. KN 62 reduced the ovulatory efficiency of hCG-treated ovaries in vitro during perfusion (hCG + 10(-7) mol KN 62 l-1: 32.9%; hCG: 80.9%). Furthermore, it significantly reduced the ovulatory efficiency of PGF2 alpha-treated ovaries (PGF2 alpha + KN 62 = 21.5%; PGF2 alpha = 59.9%).(ABSTRACT TRUNCATED AT 250 WORDS)
（i）钙/钙调蛋白依赖性蛋白激酶II介导的信号转导在人绒毛膜促性腺激素（hCG）诱导排卵中的作用；（ii）在排卵诱导的整体过程中，花生四烯酸代谢物、一氧化氮与钙/钙调蛋白依赖性蛋白激酶II之间是否存在关联。在原位插入卵巢动脉，然后切除卵巢并进行体外灌注。计算每个实验的排卵效率（[排卵卵泡数/直径大于1.5毫米的成熟卵泡数]×100）。在没有促性腺激素的情况下，钙/钙调蛋白依赖性蛋白激酶II底物可诱导排卵（钙/钙调蛋白依赖性蛋白激酶II底物：66.3%；对照组：0%）。在接下来的实验中，实验卵巢的灌注培养基中添加了钙/钙调蛋白依赖性蛋白激酶II的强效抑制剂KN 62，而对侧卵巢作为对照。用hCG（50国际单位/（150毫升）-1）诱导两侧卵巢排卵，并持续灌注8小时。在第三个实验中，分别在有和没有KN 62的情况下用前列腺素F2α（PGF2α）灌注卵巢，而对侧卵巢仅用培养基灌注。在灌注过程中，KN 62降低了体外hCG处理卵巢的排卵效率（hCG + 10-7摩尔/升KN 62：32.9%；hCG：80.9%）。此外，它还显著降低了PGF2α处理卵巢的排卵效率（PGF2α + KN 62 = 21.5%；PGF2α = 59.9%）。（摘要截断于250字）
