A new subclass of the luteinizing hormone/chorionic gonadotropin receptor lacking exon 10 messenger RNA in the new world monkey (Platyrrhini) lineage
A new subclass of the luteinizing hormone/chorionic gonadotropin receptor lacking exon 10 messenger RNA in the new world monkey (Platyrrhini) lineage
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DOI：
10.1095/biolreprod.102.014902
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发表时间：
2003-07-01
影响因子：
3.6
通讯作者：
Simoni, M
中科院分区：
文献类型：
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作者：
Gromoll, J;Wistuba, J;Simoni, M
黄体生成素受体（LHR）在胚胎性分化和配子发生过程中作为LH和CG作用的介导者起着重要作用。在性腺功能减退的男性患者，我们最近证明，外显子10的基因组缺失，位于铰链区的细胞外结构域，导致LH和hCG的行动歧视。在普通绒猴（Calltithrix jacchus）中，LHR的外显子10在mRNA水平上自然缺失。为了研究这是否是一个孤立的物种特异性现象，我们进行了系统发育筛选，寻找LHR外显子10 mRNA的存在下，在一些灵长类动物物种的灵长类动物进化的主要谱系代表。通过RT-PCR从睾丸组织中扩增包含外显子10的表达的LHR区域，克隆并测序。此外，我们对选定的新世界和旧世界灵长类动物的LHR进行了Southern印迹分析。结果显示，外显子10 mRNA在完整的新世界猴（Platyrrhini）谱系中缺乏，但在更原始和更高级的灵长类动物中都存在。然而，外显子10似乎存在于基因组水平，认为剪接失败可能是由于基因组突变或缺乏适当的剪接因子。考虑到，在人类中，LH是远远低于hCG的LHR缺乏外显子10的活性，我们解决了这样一个受体的存在是否有任何后果的双激素LH/CG系统存在于Platyrrhini的问题。利用已知绒猴CG β cDNA的特异性引物，通过RT-PCR方法从雄性普通绒猴脑垂体中扩增出CG 0亚基cDNA，但未能扩增出LH 0亚基cDNA，提示绒猴脑垂体CG可能具有生理功能。总之，我们第一次证明了LH mRNA没有外显子10是天然野生型LHR的Platyrrhini血统。我们建议，这种LHR代表一个新的受体亚类，应命名为LHR II型。此外，绒猴垂体中CG 0的高表达表明CG在这些灵长类动物妊娠后的生殖功能中的生理作用。
The luteinizing hormone receptor (LHR) plays an essential role as a mediator of LH and CG action during embryonic sexual differentiation and in gametogenesis. In a hypogonadal male patient, we recently demonstrated that a genomic deletion of exon 10, located in the hinge region of the extracellular domain, results in discrimination of LH and hCG action. In the common marmoset (Calltithrix jacchus), exon 10 of the LHR is naturally missing at the mRNA level. In order to investigate whether this is an isolated species-specific phenomenon, we performed a phylogenetic screening, searching for the presence of LHR exon 10 mRNA in a number of primate species representative for the major lineages of primate evolution. The expressed LHR region encompassing exon 10 was amplified from testicular tissue by RT-PCR, cloned, and sequenced. In addition, we performed Southern blot analysis of the LHR of selected New World and Old World primates. The results revealed that exon 10 mRNA is lacking in the complete New World monkey (Platyrrhini) lineage but is present in both more primitive and more advanced primates. However, exon 10 seems to be present at the genomic level, arguing for a splicing failure possibly due to a genomic mutation or the lack of appropriate splicing factors. Considering that, in the human, LH is far less active than hCG on the LHR lacking exon 10, we addressed the question whether the existence of such a receptor has any consequences on the dual hormone LH/CG system present in Platyrrhini. Using primers specific for the known marmoset CG beta cDNA, we amplified the CG 0 subunit cDNA from male common marmoset pituitaries by RT-PCR, while LH 0 could not be amplified, suggesting a possible physiological role of pituitary CG in this species. In conclusion, we demonstrated for the first time that the LH mRNA without exon10 is the natural wild-type LHR in the Platyrrhini lineage. We propose that this LHR represents a new subclass of receptors that should be named LHR type II. In addition, the high expression of CG 0 in the marmoset pituitary suggests a physiological role of CG in the reproductive function of these primates beyond pregnancy.