Abstract

The pulsatile secretion of gonadotropin-releasing hormone (GnRH) is the key regulator of reproduction. Follicle-stimulating hormone (FSH) and luteinizing hormone (LH) are differently regulated by different pulse frequencies of GnRH. The goal of this proposal is to determine the mechanism of regulation of LH and FSH gene expression by pulsatile GnRH.
Specific Aim 1 : Determine Pulse Frequencies Determine the GnRH pulse frequencies that lead to maximal expression of LH beta and FSHbeta genes utilizing transient transfection for short-term pulsatile treatment and stable transfection for longer pulsatile treatment in the L beta T2 gonadotrope cell line.
Specific Aim 2 : Determine Signaling Cascades Determine the signal transduction pathways necessary for the induction of LHbeta versus FSHbeta genes by pulsatile GnRH. Determine which signaling molecules are activated by specific pulse frequencies and compare their activation to tonic GnRH.
Specific Aim 3 : Determine the Transcriptional Mechanisms Determine the promoter regions and transcription factors that play roles in pulsatile GnRH induction of the LHbeta and FSHbeta genes. Identify new target genes for pulsatile GnRH using DNA microarray approaches.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32HD041301-02
Application #
6526452
Study Section
Reproductive Biology Study Section (REB)
Program Officer
De Paolo, Louis V
Project Start
2002-09-01
Project End
Budget Start
2002-09-01
Budget End
2003-08-31
Support Year
2
Fiscal Year
2002
Total Cost
$43,712
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

Thackray, Varykina G; Mellon, Pamela L; Coss, Djurdjica (2010) Hormones in synergy: regulation of the pituitary gonadotropin genes. Mol Cell Endocrinol 314:192-203
McGillivray, Shauna M; Thackray, Varykina G; Coss, Djurdjica et al. (2007) Activin and glucocorticoids synergistically activate follicle-stimulating hormone beta-subunit gene expression in the immortalized LbetaT2 gonadotrope cell line. Endocrinology 148:762-73
Coss, Djurdjica; Hand, Cameron M; Yaphockun, Karen K J et al. (2007) p38 mitogen-activated protein kinase is critical for synergistic induction of the FSH(beta) gene by gonadotropin-releasing hormone and activin through augmentation of c-Fos induction and Smad phosphorylation. Mol Endocrinol 21:3071-86
Zhang, Hao; Bailey, Janice S; Coss, Djurdjica et al. (2006) Activin modulates the transcriptional response of LbetaT2 cells to gonadotropin-releasing hormone and alters cellular proliferation. Mol Endocrinol 20:2909-30
Coss, Djurdjica; Thackray, Varykina G; Deng, Chu-Xia et al. (2005) Activin regulates luteinizing hormone beta-subunit gene expression through Smad-binding and homeobox elements. Mol Endocrinol 19:2610-23
Bailey, Janice S; Rave-Harel, Naama; McGillivray, Shauna M et al. (2004) Activin regulation of the follicle-stimulating hormone beta-subunit gene involves Smads and the TALE homeodomain proteins Pbx1 and Prep1. Mol Endocrinol 18:1158-70
Rave-Harel, Naama; Givens, Marjory L; Nelson, Shelley B et al. (2004) TALE homeodomain proteins regulate gonadotropin-releasing hormone gene expression independently and via interactions with Oct-1. J Biol Chem 279:30287-97
Coss, Djurdjica; Jacobs, Suzanne B R; Bender, Cheryl E et al. (2004) A novel AP-1 site is critical for maximal induction of the follicle-stimulating hormone beta gene by gonadotropin-releasing hormone. J Biol Chem 279:152-62
Jacobs, Suzanne B R; Coss, Djurdjica; McGillivray, Shauna M et al. (2003) Nuclear factor Y and steroidogenic factor 1 physically and functionally interact to contribute to cell-specific expression of the mouse Follicle-stimulating hormone-beta gene. Mol Endocrinol 17:1470-83