Activation of two different but complementary biochemical pathways stimulates release of hypothalamic luteinizing hormone-releasing hormone.
Activation of two different but complementary biochemical pathways stimulates release of hypothalamic luteinizing hormone-releasing hormone.
复制标题
DOI：
10.1073/pnas.83.13.4932
复制
发表时间：
1986-07
影响因子：
11.1
通讯作者：
S. Ojeda;H. Urbanski;K. H. Katz;M. Costa;P. Conn
中科院分区：
文献类型：
--
作者：
S. Ojeda;H. Urbanski;K. H. Katz;M. Costa;P. Conn
有证据表明，去甲肾上腺素/前列腺素E2（PGE 2）/cAMP途径参与调节促黄体生成素释放激素（LHRH）的分泌。本实验的目的是确定是否LHRH释放从未成熟大鼠下丘脑也可以通过激活蛋白激酶C刺激。将来自28日龄雌性大鼠的正中隆起与二辛酰甘油（一种选择性激活完整细胞中蛋白激酶C的合成二酰基甘油）或4 β-佛波醇12 β-肉豆蔻酸酯13 α-乙酸酯（另一种蛋白激酶C激活剂）在体外孵育。这两种药物增加LHRH的释放，二辛酰甘油的反应比佛波酯更明显。这种蛋白激酶C的直接激活并不伴随着PGE 2形成的变化。去甲肾上腺素、前列腺素E2或毛喉素（一种腺苷酸环化酶的刺激剂）激活前列腺素E2/cAMP通路可增加LHRH的释放。二辛酰甘油或佛波酯与去甲肾上腺素，前列腺素E2或毛喉素导致LHRH释放的叠加效应，表明两种途径共存。磷脂酶C通过形成二酰基甘油激活蛋白激酶C，增加LHRH和PGE 2的释放。这表明由神经递质输入引起的内源性磷脂酶C活性的增加可能导致蛋白激酶C的激活和PGE 2的形成。吲哚美辛阻断环氧合酶活性可消除磷脂酶C诱导的PGE 2释放。相同的处理仅使LHRH反应降低50%，表明蛋白激酶C活化可在PGE 2合成不存在的情况下引起LHRH释放。这表明，正中隆起的大鼠具有蛋白激酶C依赖的途径，正耦合到LHRH的释放和补充PGE 2/cAMP依赖的机制。然而，去甲肾上腺素似乎不是负责激活蛋白激酶C通路的神经递质。同时激活这两种途径可能提供了一种机制，通过这种机制，LHRH分泌大量增加，如在第一次发情前期的下午。
Evidence exists that a norepinephrine/prostaglandin E2 (PGE2)/cAMP pathway is involved in the regulation of luteinizing hormone-releasing hormone (LHRH) secretion. The aim of the present experiments was to determine if release of LHRH from the immature rat hypothalamus could also be stimulated by activation of protein kinase C. Median eminences from 28-day-old female rats were incubated in vitro with either dioctanoylglycerol (a synthetic diacylglycerol that selectively activates protein kinase C in intact cells) or 4 beta-phorbol 12 beta-myristate 13 alpha-acetate (another protein kinase C activator). Both agents increased LHRH release, the response to dioctanoylglycerol being more pronounced than that to the phorbol ester. This direct activation of protein kinase C was not accompanied by changes in PGE2 formation. Activation of the PGE2/cAMP pathway by either norepinephrine, PGE2, or forskolin (a stimulator of adenylate cyclase) increased LHRH release. Dioctanoylglycerol or phorbol ester in conjunction with either norepinephrine, PGE2 or forskolin resulted in an additive effect on LHRH release suggesting coexistence of both pathways. Phospholipase C, which activates protein kinase C via formation of diacylglycerol, increased the release of both LHRH and PGE2. This suggests that an increase in endogenous phospholipase C activity caused by neurotransmitter inputs may lead to both activation of protein kinase C and PGE2 formation. Blockade of cyclooxygenase activity by indomethacin obliterated phospholipase C-induced PGE2 release. The same treatment reduced the LHRH response by only 50% indicating that protein kinase C activation can cause LHRH release in the absence of PGE2 synthesis. It is suggested that the median eminence of the rat possesses a protein kinase C-dependent pathway that is coupled positively to LHRH release and complements PGE2/cAMP-dependent mechanisms. Norepinephrine, however, does not appear to be the neurotransmitter responsible for activating the protein kinase C pathway. Simultaneous activation of both pathways may provide a mechanism by which a large increase in LHRH secretion occurs, such as in the afternoon of first proestrus.