EPIGENOMIC RELATIONSHIP TO A SEX DIFFERENCE IN HYPOTHALAMIC LHRH MRNA EXPRESSION

下丘脑 LHRH mRNA 表达性别差异的表观基因组关系

• 批准号: 8173164
• 负责人: Ei Terasawa-Grilley
• 金额: $ 3.1万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8173164
• 关键词: 5' Flanking Region; Adult; Age-Years; Androgens; Animals; Area; Binding; Complex; Computer Retrieval of Information on Scientific Projects Database; DNA; DNA Modification Process; Drug or chemical Tissue Distribution; Endocrinology; Epigenetic Process; Estrogens; Exhibits; Female; Funding; Gene Expression; Genes; Gonadal Steroid Hormones; Gonadotropin Hormone Releasing Hormone; Grant; Hypothalamic structure; Institution; Investigation; KISS1 gene; KISS1R gene; Macaca mulatta; Medial; Messenger RNA; Methylation; Modification; Monkeys; Neurons; Neurosecretory Systems; Ovarian; Pathology; Phase; Preoptic Areas; Primates; RNA; Relative (related person); Reporting; Research; Research Personnel; Resources; Services; Sex Characteristics; Signal Transduction; Source; System; Transcription Initiation Site; Transplantation; United States National Institutes of Health; epigenomics; male; programs; reproductive function; research study; sex; transcription factor; trend

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Objective: To investigate whether sex differences exist in gene expression of LHRH as well as other neuronal systems known to influence LHRH neuronal activity. Luteinizing-hormone releasing hormone (LHRH) is a key regulator of reproductive function. Adult rhesus monkey (macaca mulatta) LHRH gene expression in the hypothalamus is regulated by gonadal steroids, primarily estrogens in females and androgens in males. Despite this distinction, there is no report of how sex-specific signals regulate LHRH gene expression. RNA and DNA were collected from the medial basal hypothalamus (MBH) and preoptic area (POA) of gonadally intact adult male (n=5, 11.0¿1.7 years of age) and female (n=5, 11.2¿2.0 years of age) rhesus monkeys. The phases of ovulatory cycle in the female monkeys were unknown, as they were obtained from the tissue distribution program. Using quantitative PCR, we found that LHRH mRNA levels in the MBH are significantly lower in males compared to females (p0.05), but there was no difference in the POA. Moreover, we found that there were no sex differences in GAD65, GAD67, NPY, KiSS-1, and GPR54 mRNA in either area. Because there is no permanent sexual differentiation in the primate hypothalamic LHRH neurosecretory system, i.e., LH surges could be induced by ovarian transplantation in orchidectomized adult male monkeys (Norman and Spies Endocrinology 118:2608-2610, 1986), it is possible that an epigenetic mechanism regulates the sex difference in LHRH gene expression. In the second experiment we investigated if CpG methylation, a covalent modification of DNA that influences transcription factor binding and gene expression, was different between the sexes. Preliminary investigations revealed a trend (p0.1) with males exhibiting higher CpG methylation than females in the 5' flanking region of the LHRH gene. This methylation is in a CpG rich region -2100/-1700 relative to the transcription start site in the rhesus LHRH gene. Collectively, these results indicate that there is a significant sex difference in LHRH mRNA levels in rhesus monkeys and that this may be related to a difference in CpG methylation. It is concluded that epigenomic modifications are factors in the complex orchestration of LHRH gene expression in primates. This research used WNPRC Animal Services (Pathology Services).

该副本是使用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这是调查员的机构。 目的：研究LHRH基因表达以及已知影响LHRH神经元活性的其他神经元系统中是否存在性别差异。 黄体生成荷尔蒙释放马龙（LHRH）是生殖功能的关键调节剂。下丘脑中的成年恒河猴（Macaca mulatta）LHRH基因表达受性腺类固醇，雌性的原发性雌激素和雄性雄激素的调节。尽管有这种区别，但尚无关于性别特异性信号如何调节LHRH基因表达的报道。 RNA和DNA是从基底下丘脑（MBH）和巨大的成年男性（n = 5，11.0€1.7岁）和女性（n = 5，11.2€2.0 2.0岁）的鼠尾草猴子的鼠尾草中收集的。雌性猴子的排卵周期阶段尚不清楚，因为它们是从组织分布程序中获得的。使用定量PCR，我们发现与女性相比，男性中MBH中的LHRH mRNA水平明显降低（P0.05），但POA没有差异。此外，我们发现任何一个地区的GAD65，GAD67，NPY，KISS-1和GPR54 mRNA都没有性别差异。因为私人下丘脑LHRH神经分泌系统中没有永久性差异化，因此，LH的激增可能是通过卵巢移植的卵巢移植而诱发的，这可能会导致性别差异。在第二个实验中，我们研究了性别之间的CpG甲基化（影响转录因子结合和基因表达的DNA的共价修饰）在性别之间有所不同。初步研究表明，在LHRH基因的5'侧翼区域中，男性的CpG甲基化表现出更高的CpG甲基化趋势（P0.1）。相对于LHRH基因中的转录起始位点，该甲基化在富含CpG的区域-2100/-1700中。总的来说，这些结果表明，恒河猴的LHRH mRNA水平存在显着性差异，这可能与CpG甲基化的差异有关。结论是，表观基因组修饰是LHRH基因复杂编排的因素。在私人中的表达。 这项研究使用了WNPRC动物服务（病理服务）。