Glucocorticoids suppress basal (but not interleukin-1-supported) ovarian phospholipase A2 activity: evidence for glucocorticoid receptor-mediated regulation.
Glucocorticoids suppress basal (but not interleukin-1-supported) ovarian phospholipase A2 activity: evidence for glucocorticoid receptor-mediated regulation.
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糖皮质激素抑制基础（但不是白细胞介素 1 支持的）卵巢磷脂酶 A2 活性：糖皮质激素受体介导调节的证据。
DOI：
10.1016/s0303-7207(98)00003-3
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发表时间：
1998
影响因子：
4.1
通讯作者：
Adashi,EY
中科院分区：
文献类型：
--
作者：
Kol,S;Ben-Shlomo,I;Payne,DW;Ando,M;Rohan,RM;Adashi,EY
排卵可能构成一个周期性的炎症样过程，其中白细胞介素（IL）-1的表达增加和白藜芦醇的生物合成可能是确定的必然结果。在这篇文章中，我们假设糖皮质激素是一种有效的抗炎成分，可能通过干扰卵巢IL-1驱动的前列腺素生物合成而发挥抗排卵作用。为了验证这一假设，我们研究了地塞米松治疗对卵巢磷脂酶A2（PLA 2）活性的影响，PLA 2是前列腺素生物合成中的事件限制酶，并对分泌型和胞浆型PLA 2（分别为sPLA 2和cPLA 2）的基因表达模式。未成熟大鼠的整个卵巢分散液在无血清条件下培养48小时，地塞米松的存在或不存在。培养结束时，测定细胞超声处理物和条件培养基中的PLA 2活性。采用溶液杂交/RNA酶保护试验对sPLA 2和cPLA 2转录本进行平行检测。用地塞米松处理整个卵巢分散液使基础细胞和细胞外PLA 2活性分别显著降低（P<0.005）至对照组的27%和40%。还注意到sPLA 2（但不是cPLA 2）转录物的基础稳态水平降低了5倍。与地塞米松共处理产生了对IL-1刺激的cPLA 2转录的完全抑制，但对IL-1支持的细胞和细胞外PLA 2活性或sPLA 2转录没有抑制作用。糖皮质激素受体拮抗剂（RU 486）阻断地塞米松抑制基础sPLA 2转录和细胞外PLA 2活性的能力。地塞米松的抑制作用证明是糖皮质激素特异性的，因为醛固酮和17β-雌二醇没有作用。综上所述，这些观察结果表明，地塞米松能够抑制基础（但不是IL-1支持）卵巢PLA 2活性，糖皮质激素受体介导的作用，部分原因是sPLA 2基因表达的减少。我们的研究结果进一步表明，sPLA 2和cPLA 2的差异调节，他们可能在其相对贡献卵巢前列腺素的生物合成一般，特别是PLA 2的活性不同。在一定程度上，IL-1在排卵过程中起着核心作用，这些研究结果反驳了糖皮质激素过量诱导的慢性无排卵状态是由于卵巢IL-1依赖性PLA 2活性受到抑制的观点。
Ovulation may constitute a cyclic, inflammatory-like process, wherein the increased expression of interleukin (IL)-1 and the biosynthesis of prostaglandins may be established corollaries. In this communication we hypothesize that glucocorticoids, potent anti-inflammatory principles, may exert an antiovulatory effect by interfering with ovarian IL-1-driven prostaglandin biosynthesis. To test this hypothesis, we examined the effect of treatment with dexamethasone on the activity of ovarian phospholipase A2(PLA2), the event-limiting enzyme in prostaglandin biosynthesis, and on the gene expression pattern of secretory and cytosolic PLA2(sPLA2and cPLA2, respectively). Whole ovarian dispersates from immature rats were cultured under serum-free conditions for 48 h in the absence or presence of dexamethasone. At the conclusion of this culture period, PLA2activity was determined in cell sonicates and conditioned media. Parallel probing for sPLA2and cPLA2transcripts was also undertaken using a solution hybridization/RNAse protection assay. Treatment of whole ovarian dispersates with dexamethasone produced a significant (P<0.005) decrease in basal cellular and extracellular PLA2activity to 27 and 40% of controls, respectively. A 5-fold decrease in the basal steady state levels of sPLA2(but not cPLA2) transcripts was also noted. Co-treatment with dexamethasone produced complete inhibition of IL-1-stimulated cPLA2transcripts but not of IL-1-supported cellular and extracellular PLA2activity or sPLA2transcripts. A glucocorticoid receptor antagonist (RU486), blocked the ability of dexamethasone to inhibit basal sPLA2transcripts and extracellular PLA2activity. The inhibitory effect of dexamethasone proved glucocorticoid-specific in that aldosterone and 17β-estradiol were without effect. Taken together, these observations suggest that dexamethasone is capable of inhibiting basal (but not IL-1-supported) ovarian PLA2activity, a glucocorticoid receptor-mediated effect due, in part, to a decrease in sPLA2gene expression. Our findings further suggest that sPLA2and cPLA2are differentially regulated and that they may well differ in their relative contribution to ovarian prostaglandin biosynthesis in general and to PLA2activity in particular. To the extent that IL-1 plays a central role in the ovulatory process, these findings argue against the view that the chronic anovulatory state induced by glucocorticoid excess is due, if only in part, to suppression of ovarian IL-1-dependent PLA2activity.