LH and hCG action on the same receptor results in quantitatively and qualitatively different intracellular signalling.
LH and hCG action on the same receptor results in quantitatively and qualitatively different intracellular signalling.
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DOI：
10.1371/journal.pone.0046682
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Simoni M
中科院分区：
文献类型：
--
作者：
Casarini L;Lispi M;Longobardi S;Milosa F;La Marca A;Tagliasacchi D;Pignatti E;Simoni M
人促黄体生成素(HLH)和绒毛膜促性腺激素(HCG)作用于同一受体(LHCGR)，但它们是否引起相同的细胞和分子反应尚不清楚。这项研究首次比较了细胞信号通路的激活和基因表达对hLH和hCG的反应。应用重组人促黄体生成素和重组人绒毛膜促性腺激素释放激素，研究了永久表达LHCGR(COS-7/LHCGR，hGL5/LHCGR)的COS-7和hGL5细胞产生cAMP的动力学，以及原代人颗粒细胞(HGLC)cAMP、ERK1/2、AKT活化和孕酮产生的动力学。在存在或不存在ERK或AKT途径抑制剂的情况下，测量选定的靶基因的表达。在COS7/LHCGR细胞中，人绒毛膜促性腺激素的活性是人促黄体生成素的5倍(cAMP ED50分别为107.1±14.3 pm和530.0±51.2 pm)。促黄体生成素最大起效时间明显加快(促黄体生成素10min；促性腺激素1h)。在hGLC中，连续暴露于相同剂量的促性腺激素长达36小时，显示细胞内cAMP的产生是振荡的，并且hCG和HLH的cAMP产量显著高于hCG。相反，磷酸化ERK1/2和-AKT的激活作用比hCG更强，并且被hLH所维持。ERK1/2和AKT抑制可解除hLH对NRG1表达的抑制，但不能抑制hCG对NRG1表达的抑制；ERK1/2抑制可显著增加hCG刺激的细胞色素P19A1(芳香酶)的表达。我们得出的结论是：hCG对cAMP的产生有更强的作用，而hLH对ERK和AKT的激活作用更强；ii)hGLC对相等的恒定的hLH或hCG刺激做出反应，cAMP产生波动，孕酮分泌递增；以及iii)hLH和hCG靶基因的表达部分涉及不同途径的激活，取决于配体的不同。因此，LHCGR能够区分hLH和hCG的活性。
Human luteinizing hormone (hLH) and chorionic gonadotropin (hCG) act on the same receptor (LHCGR) but it is not known whether they elicit the same cellular and molecular response. This study compares for the first time the activation of cell-signalling pathways and gene expression in response to hLH and hCG. Using recombinant hLH and recombinant hCG we evaluated the kinetics of cAMP production in COS-7 and hGL5 cells permanently expressing LHCGR (COS-7/LHCGR, hGL5/LHCGR), as well as cAMP, ERK1/2, AKT activation and progesterone production in primary human granulosa cells (hGLC). The expression of selected target genes was measured in the presence or absence of ERK- or AKT-pathways inhibitors. In COS-7/LHCGR cells, hCG is 5-fold more potent than hLH (cAMP ED50: 107.1±14.3 pM and 530.0±51.2 pM, respectively). hLH maximal effect was significantly faster (10 minutes by hLH; 1 hour by hCG). In hGLC continuous exposure to equipotent doses of gonadotropins up to 36 hours revealed that intracellular cAMP production is oscillating and significantly higher by hCG versus hLH. Conversely, phospho-ERK1/2 and -AKT activation was more potent and sustained by hLH versus hCG. ERK1/2 and AKT inhibition removed the inhibitory effect on NRG1 (neuregulin) expression by hLH but not by hCG; ERK1/2 inhibition significantly increased hLH- but not hCG-stimulated CYP19A1 (aromatase) expression. We conclude that: i) hCG is more potent on cAMP production, while hLH is more potent on ERK and AKT activation; ii) hGLC respond to equipotent, constant hLH or hCG stimulation with a fluctuating cAMP production and progressive progesterone secretion; and iii) the expression of hLH and hCG target genes partly involves the activation of different pathways depending on the ligand. Therefore, the LHCGR is able to differentiate the activity of hLH and hCG.
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影响因子：
3.7
作者：
AHARONI, D;DANTES, A;AMSTERDAM, A
通讯作者：
AMSTERDAM, A
DOI：
10.1111/j.1432-1033.1996.0608r.x
发表时间：
1996-12-15
期刊：
EUROPEAN JOURNAL OF BIOCHEMISTRY
影响因子：
--
作者：
Amoresano, A;Siciliano, R;Pucci, P
通讯作者：
Pucci, P
影响因子：
4.8
作者：
Birken, S;Maydelman, Y;Hartree, AS
通讯作者：
Hartree, AS
影响因子：
3.6
作者：
Brown C;LaRocca J;Pietruska J;Ota M;Anderson L;Smith SD;Weston P;Rasoulpour T;Hixon ML
通讯作者：
Hixon ML
影响因子：
3.1
作者：
Craig, Jesse;Orisaka, Makoto;Tsang, Benjamin K.
通讯作者：
Tsang, Benjamin K.