Estrogen receptor α-induced cholecystokinin type A receptor expression in the female mouse pituitary
Estrogen receptor α-induced cholecystokinin type A receptor expression in the female mouse pituitary
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DOI：
10.1677/joe-07-0358
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发表时间：
2007-12-01
影响因子：
4
通讯作者：
Ko, CheMyong
中科院分区：
文献类型：
--
作者：
Kim, Hyun Joon;Gieske, Mary C.;Ko, CheMyong
雌激素在诱导黄体生成素激增中起关键作用。在垂体中，雌激素受体α (ER α)介导雌激素的作用，而雌激素受体α激活的下游途径尚不清楚。在这里，我们报告发现胆囊收缩素A型受体（CCK-AR）是小鼠垂体前叶中的ER α下游基因。在循环小鼠垂体中，CCK-AR mRNA在发情期下午的表达明显高于发情期。卵巢切除术（OVX）和ER α基因的零突变完全消除了CCK-AR mRNA的表达。向OVX野生型小鼠注射17 β -雌二醇可诱导CCK-AR mRNA表达恢复至发情前水平，但在OVX ERa敲除小鼠中未引起这种恢复。在培养的原代垂体前叶细胞中，诱导CCK-AR mRNA表达的模式与雌激素依赖性相同，表明雌激素直接作用于垂体细胞诱导CCK-AR表达。免疫组织学分析显示，80%以上的促性腺细胞在发情前下午表达CCK-AR。为了测试CCK-AR是否介导了雌激素对GnRH诱导的黄体生成素分泌的增敏作用，将垂体原代细胞注入雌激素，然后在CCK-AR拮抗剂洛格鲁胺存在或不存在的情况下用GnRH处理。虽然两组在GnRH治疗后均分泌LH，但洛格鲁胺治疗显著降低了LH分泌。综上所述，本研究发现CCK-AR是垂体中的ER α下游基因，并提示CCK-AR可能在垂体对GnRH反应的雌激素致敏中发挥作用。
Estrogen plays a critical role in inducing LH surge. In the pituitary, estrogen receptor alpha (ER alpha) mediates the action of estrogen, while the downstream pathway of ERa activation is yet to be elucidated. Here, we report the finding that cholecystokinin type A receptor (CCK-AR) is an ER alpha downstream gene in the mouse anterior pituitary. In the cycling mouse pituitary, the expression of CCK-AR mRNA is markedly higher in the afternoon of proestrus compared with metestrus. Both ovariectomy (OVX) and null mutation of the ER alpha gene completely abolish CCK-AR mRNA expression. Injection of 17 beta-estradiol to OVX wild-type mice induces recovery of CCK-AR mRNA expression to levels observed at proestrus, but no such recovery is induced in OVX ERa knockout mice. The same pattern of estrogen dependency in inducing CCK-AR mRNA expression was seen in cultured primary anterior pituitary cells, indicating that estrogen directly acts on pituitary cells to induce CCK-AR expression. Immunohistological analysis revealed that more than 80% of gonadotrophs express CCK-AR in the afternoon of proestrus. To test whether CCK-AR mediated the sensitizing effect of estrogen in GnRH-induced LH secretion, primary pituitary cells were primed with estrogen followed by treatment with GnRH in the presence or absence of lorglumide, a CCK-AR antagonist. While both groups secreted LH upon GnRH treatment, lorglumide treatment significantly decreased LH secretion. Taken together, this study finds CCK-AR to be an ER alpha downstream gene in the pituitary and suggests that CCK-AR may play a role in the estrogen sensitization of the pituitary response to GnRH.