Abstract

The goal of this project is to gain an understanding of the regulation of the GnRH gene in the hypothalamus.
Aim 1 is to understand the basis of neuron-specific expression of the GnRH gene. The tissue-specific actions of known proteins on the GnRH gene enhancer will be defined, and additional proteins that interact with the enhancer identified.
Aim 2 is to identify the elements and target proteins important for mediating the actions of the NMDA/NO/cGMP or PKC pathways to repress transcription of the GnRH gene.
Aim 3 is to develop a new GnRH cell model system using transgenic animal technologies, in which the transforming oncogene can be switched off in culture to allow the cells to become postmitotic.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK044838-09
Application #
2734116
Study Section
Biochemical Endocrinology Study Section (BCE)
Program Officer
Sato, Sheryl M
Project Start
1992-01-01
Project End
2001-06-30
Budget Start
1998-07-01
Budget End
1999-06-30
Support Year
9
Fiscal Year
1998
Total Cost
Indirect Cost

  Institution

Name
University of California San Diego
Department
Obstetrics & Gynecology
Type
Schools of Medicine
DUNS #
077758407
City
La Jolla
State
CA
Country
United States
Zip Code
92093

  Publications

Ryan, Genevieve E; Malik, Shaddy; Mellon, Pamela L (2018) Antiandrogen Treatment Ameliorates Reproductive and Metabolic Phenotypes in the Letrozole-Induced Mouse Model of PCOS. Endocrinology 159:1734-1747
Que, Xuchu; Hung, Ming-Yow; Yeang, Calvin et al. (2018) Oxidized phospholipids are proinflammatory and proatherogenic in hypercholesterolaemic mice. Nature 558:301-306
Schoeller, Erica L; Clark, Daniel D; Dey, Sandeepa et al. (2016) Bmal1 Is Required for Normal Reproductive Behaviors in Male Mice. Endocrinology 157:4914-4929
Hoffmann, Hanne M; Trang, Crystal; Gong, Ping et al. (2016) Deletion of Vax1 from Gonadotropin-Releasing Hormone (GnRH) Neurons Abolishes GnRH Expression and Leads to Hypogonadism and Infertility. J Neurosci 36:3506-18
Hoffmann, Hanne M; Mellon, Pamela L (2016) A small population of hypothalamic neurons govern fertility: the critical role of VAX1 in GnRH neuron development and fertility maintenance. Neurosci Commun (Houst) 2:
Skowronska-Krawczyk, Dorota; Zhao, Ling; Zhu, Jie et al. (2015) P16INK4a Upregulation Mediated by SIX6 Defines Retinal Ganglion Cell Pathogenesis in Glaucoma. Mol Cell 59:931-40
Xie, Huimin; Hoffmann, Hanne M; Meadows, Jason D et al. (2015) Homeodomain Proteins SIX3 and SIX6 Regulate Gonadotrope-specific Genes During Pituitary Development. Mol Endocrinol 29:842-55
Breen, Kellie M; Mellon, Pamela L (2014) Influence of stress-induced intermediates on gonadotropin gene expression in gonadotrope cells. Mol Cell Endocrinol 385:71-7
Glidewell-Kenney, Christine A; Trang, Crystal; Shao, Paul P et al. (2014) Neurokinin B induces c-fos transcription via protein kinase C and activation of serum response factor and Elk-1 in immortalized GnRH neurons. Endocrinology 155:3909-19
Hoffmann, Hanne M; Tamrazian, Anika; Xie, Huimin et al. (2014) Heterozygous deletion of ventral anterior homeobox (vax1) causes subfertility in mice. Endocrinology 155:4043-53

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