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FETAL/POSTNATAL REGULATION OF GH RECEPTOR EXPRESSION

GH 受体表达的胎儿/产后调节

基本信息

批准号：
6177167
负责人：
Ram K. Menon
金额：
$ 10.89万
依托单位：
CHILDREN'S HOSP PITTSBURGH/UPMC HLTH SYS
依托单位国家：
美国
项目类别：
财政年份：
1996
资助国家：
美国
起止时间：
1996-06-01 至 2002-01-31
项目状态：
已结题

项目摘要

Growth hormone (GH) is essential for postnatal growth in animals. At the cellular level GH elicits its actions by initially binding to a cell surface protein termed the growth hormone receptor (GHR). A variety of factors influence the expression of the GHR; GHR is virtually undetectable in fetal tissues while its expression increases dramatically during postnatal life. The factors controlling the developmentally-regulated expression of the GHR are not known. I have identified a novel enhancer element in the promoter-regulatory region of the murine GH receptor gene which exhibits developmentally-regulated DNA-binding activity in liver. Furthermore, the functional activity of this enhancer element in transient transfection assays is also developmentally-regulated. I HYPOTHESIZE that the identified enhancer element with its cognate trans-acting factor(s) play a role in the developmentally-regulated expression of the GHR gene. This proposal seeks SPECIFICALLY to elucidate the molecular mechanisms controlling the developmentally-regulated expression of the GHR gene. The experimental strategy detailed in this proposal is designed to test the role of the identified enhancer element in the developmentally-regulated expression of the GHR gene by site-directed mutagenesis, transient transfection assays of fetal and adult hepatocytes using chimeric reporter gene constructs, and by mapping of the DNase I hypersensitivity sites in the 5' flanking region. Following a preliminary biochemical characterization of the DNA-binding protein(s), the identity of these trans-acting factor(s) will be ascertained by cloning the cDNA encoding the genes for these putative transcription factor(s). These studies will (a) delineate the molecular basis for alterations in expression of the GHR gene in disorders of growth such as genetic short stature, intra-uterine growth retardation and malnutrition, enabling (b)the design of novel diagnostic tools and more effective treatment strategies for these disorders of growth and development in the human.

生长激素（GH）是动物出生后生长所必需的。在

项目成果

期刊论文数量（27）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Molecular defects in the growth hormone-IGF axis.

生长激素-IGF 轴的分子缺陷。

DOI：
10.1007/bf02760700
发表时间：
2005
期刊：
Indian journal of pediatrics
影响因子：
4.3
作者：
Lee,Joyce;Menon,RamK
通讯作者：
Menon,RamK

Esterase 1 is a novel transcriptional repressor of growth hormone receptor gene expression: a unique noncatalytic role for a carboxyesterase protein.

Esterase 1 是一种生长激素受体基因表达的新型转录抑制因子：对羧酸酯酶蛋白具有独特的非催化作用。

DOI：
10.1210/me.2011-0097
发表时间：
2011
期刊：
Molecular endocrinology (Baltimore, Md.)
影响因子：
0
作者：
Sun,Jinhong;Kumar,PAnil;Thimmarayappa,Jamuna;Saini,Natinder;Goel,Pooja;Maures,Travis;Lu,Chunxia;Menon,RamK
通讯作者：
Menon,RamK

Identification and characterization of single strand DNA-binding protein that represses growth hormone receptor gene expression.

抑制生长激素受体基因表达的单链 DNA 结合蛋白的鉴定和表征。

DOI：
10.1210/mend.11.9.9967
发表时间：
1997
期刊：
Molecular endocrinology (Baltimore, Md.)
影响因子：
0
作者：
Menon,RK;Cheng,H;Singh,M
通讯作者：
Singh,M

Neonatal diabetes mellitus with pancreatic agenesis in an infant with homozygous IPF-1 Pro63fsX60 mutation.

DOI：
10.1111/j.1399-5448.2009.00526.x
发表时间：
2009-11
期刊：
Pediatric diabetes
影响因子：
3.4
作者：
Thomas IH;Saini NK;Adhikari A;Lee JM;Kasa-Vubu JZ;Vazquez DM;Menon RK;Chen M;Fajans SS
通讯作者：
Fajans SS

Hyperinsulinemic hypoglycemia of infancy. Recent insights into ATP-sensitive potassium channels, sulfonylurea receptors, molecular mechanisms, and treatment.

婴儿期高胰岛素低血糖。