Role of cAMP signaling in the mediation of dopamine-induced stimulation of GnRH secretion via D1 dopamine receptors in GT1-7 cells.
Role of cAMP signaling in the mediation of dopamine-induced stimulation of GnRH secretion via D1 dopamine receptors in GT1-7 cells.
复制标题
cAMP 信号传导在 GT1-7 细胞中通过 D1 多巴胺受体介导多巴胺诱导的 GnRH 分泌刺激中的作用。
DOI：
10.1159/000080519
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发表时间：
2004
影响因子：
4.1
通讯作者：
Weiner,RichardI
中科院分区：
文献类型：
--
作者：
Yoshida,Hiroshi;Paruthiyil,Sreenivasan;Butler,Paul;Weiner,RichardI
药理学上增加环磷酸腺苷（cAMP）水平在GT 1促性腺激素释放激素（GnRH）细胞系增加GnRH的分泌。多巴胺（DA）通过与腺苷酸环化酶正偶联的DA受体增加GT 1细胞的GnRH分泌。然后，我们询问是否抑制DA诱导的cAMP增加会阻断DA对GnRH释放的刺激作用。cAMP特异性磷酸二酯酶（PDE 4D 1）的表达用于遗传方法，以抑制DA诱导的cAMP水平增加。用表达PDE 4D 1的腺病毒载体（Ad）（PDE-Ad）感染细胞，或者对于对照，用空Ad（Null-Ad）感染细胞。感染PDE-Ad可完全阻断Forskolin对GnRH分泌和[Ca 2+] i的刺激作用，并减少大部分cAMP向培养液中的释放。相比之下，虽然PDE-Ad感染几乎所有的DA诱导的细胞外cAMP的增加，释放的GnRH和[Ca 2+] i的增加仅延迟约15分钟。GT 1细胞表达的D1 DA受体，这是积极耦合到腺苷酸环化酶，但不是D5 DA受体。这些数据表明，DA诱导的GnRH分泌的初始阶段依赖于cAMP水平的增加。然而，似乎另外的非cAMP调节的信号通路参与通过D1 DA受体刺激GnRH释放。
Pharmacologically increasing cyclic adenosine monophosphate (cAMP) levels in GT1 gonadotropin-releasing hormone (GnRH) cell lines increased the secretion of GnRH. Dopamine (DA) increased the GnRH secretion in GT1 cells via a DA receptor positively coupled to adenylate cyclase. We then asked whether inhibition of the DA-induced increase in cAMP would block the stimulatory effect of DA on GnRH release. Expression of the cAMP-specific phosphodiesterase (PDE4D1) was used in a genetic approach to inhibit the DA-induced increase in cAMP levels. Cells were infected with an adenovirus vector (Ad) expressing PDE4D1 (PDE-Ad) or, for controls, with an empty Ad (Null-Ad). Infection with the PDE-Ad completely blocked the forskolin-induced stimulation of GnRH secretion and [Ca 2+] i and decreased the majority of the release of cAMP into the culture medium. In contrast, although PDE-Ad infection blocked virtually all of the DA-induced increase in extracellular cAMP, the release of GnRH and the increase in [Ca 2+] i were only delayed for approximately 15 min. GT1 cells express the D1 DA receptor which is positively coupled to adenylate cyclase but not the D5 DA receptor. These data suggest that the initial phase of the DA-induced secretion of GnRH is dependent on an increase in cAMP levels. However, it appears that an additional non-cAMP-regulated signaling pathway is involved in the stimulation of GnRH release via the D1 DA receptor.