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Role of Dicer in Gonadotrope and Reproductive Function

Dicer 在促性腺激素和生殖功能中的作用

基本信息

批准号：
8458899
负责人：
T. RAJENDRA KUMAR
金额：
$ 7.17万
依托单位：
UNIVERSITY OF KANSAS MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-04-16 至 2014-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8458899
关键词：
3&apos Untranslated Regions Activin Receptor Activins Affect Amenorrhea Anterior Pituitary Gland Applications Grants Binding Biogenesis Cattle Cell Line Cell Separation Clinical Computer Simulation Defect Development Diagnosis Disease Double-Stranded RNA Embryo Endoribonucleases Event Family Fertility Fluorescence Follicle Stimulating Hormone Gametogenesis Gene Expression Gene Expression Regulation Genes Genetic Genetic Models Genetic Transcription Glycoproteins Goals Gonadal Steroid Hormones Gonadotrope Cell Gonadotropin Hormone Releasing Hormone Gonadotropins Growth Home environment Hormones Hypothalamic structure In Vitro Infertility Knowledge Label Lead Lesion Luteinizing Hormone Mediating Messenger RNA MicroRNAs Molecular Mouse Strains Mus Ovarian Hyperstimulation Syndrome Peptides Phenotype Physiology Pituitary Gland Play Population Positioning Attribute Post-Transcriptional Regulation Protein Biosynthesis Proteins Regulation Regulator Genes Reproduction Research Role Secondary to Small Interfering RNA Small RNA Steroid biosynthesis Syndrome Technology Testing Tissues Transcription Factor 3 Transcriptional Regulation Transgenes Untranslated Regions Work base cell type combinatorial endonuclease III endoribonuclease human DICER1 protein improved in vitro Model in vivo inhibin mRNA Stability mouse model novel novel therapeutics promoter public health relevance reproductive reproductive function

项目摘要

DESCRIPTION (provided by applicant): Gonadotropes synthesize and secrete heterodimeric glycoproteins luteinizing hormone (LH) and follicle stimulating hormone (FSH) that are critical for reproductive function. The genes encoding the common alpha subunit (Cga) and the hormone-specific beta subunits (Lhb and Fshb) are coordinately regulated by hypothalamic gonadotropin-releasing hormone, steroids and gonadal peptides, inhibin and activin. Although a wealth of knowledge has accumulated on transcriptional control of gonadotropin beta subunits, post- transcriptional mechanisms of these genes are unknown. Recently, micro RNAs (miRNAs) produced by Dicer, an RNA endonuclease III, have emerged as key regulators of gene expression, mRNA stability and protein synthesis. Knowledge on miRNAs that regulate gonadotrope and consequently reproductive function is lacking. Our long-term research goal is to elucidate the in vivo mechanisms that regulate gonadotropin synthesis and secretion. The central hypothesis is that Dicer is a key factor in miRNA biogenesis in gonadotropes and plays essential roles in gonadotropin synthesis and consequently reproductive function. In Specific Aim 1, we will conditionally delete Dicer exclusively in gonadotropes by cre-lox technology and analyze gonadotropin synthesis and secretion. Additionally, we will use novel mouse strains, in which gonadotropes are labeled with GFP on a normal or activin receptor-II (Acvr2) null genetic background. Pure populations of gonadotropes will be isolated from these mice by cell sorting based on GFP fluorescence and miRNAs regulated by Acvr2 identified. In Specific Aim 2, reproductive phenotypes secondary to changes in gonadotropins as a result of Dicer deletion in gonadotropes will be determined. These studies should provide new knowledge on Dicer - dependent miRNAs in gonadotropes and identify novel post-transcriptional mechanisms for gonadotropin secretion. Delineation of mechanisms of gonadotropin secretion is fundamental to physiology of reproduction and offers long-term clinical benefits of diagnosing and treating gonadotropin-dependent fertility/infertility disorders.

描述（由申请人提供）：促性腺激素合成并分泌异二聚体糖蛋白，促黄体生成素（LH）和促卵泡激素（FSH），这对