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PROJECT 1 - INTEGRATION OF HORMONE SIGNALING IN THE PITUITARY GONADOTROPE

项目 1 - 垂体促性腺激素信号传导的整合

基本信息

批准号：
7683478
负责人：
PAMELA L MELLON
金额：
$ 39.72万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN DIEGO
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-04-01 至 2014-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7683478
关键词：
Activins Address Androgen Antagonists Androgen Receptor Androgens Animal Model Animals Anterior Pituitary Gland Binding Brain Cell Communication Cell model Cell physiology Clinical Clinical Research Consensus Cultured Cells Development Diet Disease Endocrine Estrous Cycle Exposure to FOS gene Fatty acid glycerol esters Female Fertility Follicle Stimulating Hormone Follistatin Functional disorder Gene Deletion Gene Expression Genes Genetic Goals Gonadal Steroid Hormones Gonadotrope Cell Gonadotropin Hormone Releasing Hormone Gonadotropins Growth Factor Homeodomain Proteins Hormonal Hormones Hypothalamic Releasing Factor Hypothalamic structure In Vitro Investigation Luteinizing Hormone Mediating Medicine Modeling Molecular Mus Neurons Neurosecretory Systems Ovary Peptides Perinatal Exposure Phosphorylation Physiological Physiology Pituitary Gland Pituitary Gonadotropins Polycystic Ovary Syndrome Precocious Puberty Production Progesterone Progesterone Receptors Progestins Puberty Receptor Gene Regulation Regulatory Element Repression Reproduction Reproductive Physiology Research Project Grants Response Elements Role Science Signal Pathway Signal Transduction Site Steroid Receptors Steroids Syndrome System Technology Woman activin A activin B autocrine base early onset feeding hormone regulation human female in vivo insight mouse model offspring paracrine peptide hormone premature prenatal receptor binding reproductive reproductive function steroid hormone

项目摘要

The precise interplay of hormonal influences that governs gonadotropin hormone production by the pituitary ncludes endocrine, paracrine and autocrine actions of activin and follistatin, hypothalamic gonadotropin- ¿eleasing hormone (GnRH), and gonadal steroid hormones. Our focus will be the cellular and molecular mechanisms of activin, GnRH, and steroid hormone regulation of the pituitary gonadotropins: luteinizing hormone (LH) and follicle-stimulating hormone (FSH), using cultured cells in vitro, and their roles in physiology and pathophysiology, in vivo, using targeted gene deletion in mice. In Aim 1, we will focus on the regulation of the gonadotropin genes by activin, its interactions with GnRH, and the physiological role of activin signaling in the gonadotrope, in vivo, in targeted Smad-deficient mice. In Aim 2, we address the roles of progestins and androgens in both negative and positive regulation of the gonadotropin genes and their nteractions with activin signaling. Further, we will utilize targeted disruption of the progesterone and androgen receptor genes, in vivo, to assess their role within the pituitary and brain, in normal female reproductive function. Both clinical and animal studies underscore the prenatal origin of premature puberty and polycystic ovary syndrome with the common thread being abnormal androgen exposure in utero. We will use models of high-fat feeding and in utero exposure to androgens to invesigate the hypothesis that androgens, acting through the androgen receptor, are causative for advancement of puberty and for development of the hallmarks of polycystic ovary syndrome. Our overall goal is to understand the integration of activin, GnRH, and steroid hormone action in the regulation of LH and FSH in the gonadotrope in normal and pathopysiological states. Thus, the interplay of peptide hormones, growth factors, steroids, receptors, and hypothalamic releasing factors directly and indirectly controlling gonadotropin synthesis will be investigated using the armamentarium of molecular, cellular, genetic, and mouse technologies with the goal of developing a detailed understanding of the molecular mechanisms mediating normal and disordered female reproductive function.

控制垂体产生促性腺激素的激素影响的精确相互作用