Expression of the pituitary adenylate cyclase-activating polypeptide (PACAP) type 1 receptor (PAC1R) potentiates the effects of GnRH on gonadotropin subunit gene expression.
Expression of the pituitary adenylate cyclase-activating polypeptide (PACAP) type 1 receptor (PAC1R) potentiates the effects of GnRH on gonadotropin subunit gene expression.
复制标题
DOI：
10.1016/j.bbrc.2011.05.135
复制
发表时间：
2011-07
影响因子：
3.1
通讯作者：
I. Purwana;H. Kanasaki;A. Oride;T. Mijiddorj;K. Miyazaki
中科院分区：
文献类型：
--
作者：
I. Purwana;H. Kanasaki;A. Oride;T. Mijiddorj;K. Miyazaki
我们使用L β T2促性腺细胞系检查了垂体腺苷酸环化酶激活多肽（PACAP）1型受体（PAC 1 R）对促性腺激素释放激素（GnRH）诱导的促性腺激素亚基启动子活性的影响。在模拟转染细胞中，GnRH-1使LH β和FSH β启动子分别增加2.74 ± 0.15倍和1.6 ± 0.05倍。当细胞转染PAC 1R后，LH β和FSH β启动子活性进一步增加，分别为GnRH刺激后的6.1 ± 0.87倍和2.22 ± 0.43倍。ERK磷酸化，血清反应元件（SRE）的启动子，和cAMP反应元件（CRE）的启动子刺激的GnRH也加强在PAC1R的存在下，增加量。PAC 1R过表达可显著降低GnRH对LH β和FSH β基因转录的EC50值。PACAP 6 - 38，一种PACAP受体拮抗剂，未能降低GnRH对PAC1R过表达细胞中促性腺激素启动子活性的影响，这表明通过PAC1R表达增强GnRH的作用与促性腺激素细胞中产生的PACAP的自分泌机制无关。我们目前的研究结果表明，GnRH在调节促性腺激素亚基表达的作用是由PAC1Rs的存在增强。
We examined the effect of the pituitary adenylate cyclase-activating polypeptide (PACAP) type 1 receptor (PAC1R) on gonadotropin-releasing hormone (GnRH)-induced gonadotropin subunit promoter activities using the LβT2 gonadotroph cell line. In mock transfected cells, GnRH-increased LHβ and FSHβ promoters up to 2.74 ± 0.15-fold and 1.6 ± 0.05-fold respectively. When cells were transfected with PAC1R, both LHβ and FSHβ promoter activities were further increased up to 6.1 ± 0.87-fold and 2.22 ± 0.43-fold following GnRH stimulation. ERK phosphorylation, serum response element (SRE) promoters, and cAMP response element (CRE) promoters stimulated by GnRH were also potentiated in the presence of increasing amounts of PAC1R. The EC50 values for LHβ and FSHβ gene transcription by GnRH were significantly decreased by overexpression of PAC1R. PACAP 6-38, a PACAP receptor antagonist, failed to reduce the effect of GnRH on gonadotropin promoter activities in PAC1R overexpressing cells, suggesting that the potentiation of the effects of GnRH by PAC1R expression was not related to an autocrine mechanism of PACAP produced in the gonadotrophs. Our current results show that the action of GnRH in the regulation of gonadotropin subunit expression is enhanced by the presence of PAC1Rs.