Abstract

Synthesis of FSH is critical for normal reproductive function in mammals, including humans. Although there is considerable evidence that peptide and sex steroid hormones such as activin and androgens regulate transcription of the FSHBeta gene, the molecular mechanisms of this regulation remain to be elucidated. Since it is not clear how activin and androgens influence the transcription of the FSHBeta gene, I will investigate the role of Smad proteins and the androgen receptor (AR) in the regulation of the mouse FSHBeta gene in a mouse gonadotrope cell line and in vivo using transgenic mice as outlined in the following specific aims.
Specific Aim 1 """""""" Determine whether Smads and/or AR modulate FSHBeta gene expression in LBT2 cells.
Specific Aim 2 : Characterize the interactions among Smads, AR, and Pbx/Prep homeodomain Proteins.
Specific Aim 3 : Determine whether Smads and/or AR regulate FSH Beta gene expression in mouse pituitary gonadotropes in vivo.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32DK065437-01
Application #
6693549
Study Section
Special Emphasis Panel (ZRG1-F06 (20))
Program Officer
Hyde, James F
Project Start
2003-09-01
Project End
2006-08-31
Budget Start
2003-09-01
Budget End
2004-08-31
Support Year
1
Fiscal Year
2003
Total Cost
$41,608
Indirect Cost

  Institution

Name
University of California San Diego
Department
Obstetrics & Gynecology
Type
Schools of Medicine
DUNS #
804355790
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
Thackray, Varykina G; Hunnicutt, Jennifer L; Memon, Aisha K et al. (2009) Progesterone Inhibits basal and gonadotropin-releasing hormone induction of luteinizing hormone beta-subunit gene expression. Endocrinology 150:2395-403
Sasson, Ravid; Luu, Sang H; Thackray, Varykina G et al. (2008) Glucocorticoids induce human glycoprotein hormone alpha-subunit gene expression in the gonadotrope. Endocrinology 149:3643-55
Thackray, Varykina G; Mellon, Pamela L (2008) Synergistic induction of follicle-stimulating hormone beta-subunit gene expression by gonadal steroid hormone receptors and Smad proteins. Endocrinology 149:1091-102
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
Thackray, Varykina G; McGillivray, Shauna M; Mellon, Pamela L (2006) Androgens, progestins, and glucocorticoids induce follicle-stimulating hormone beta-subunit gene expression at the level of the gonadotrope. Mol Endocrinol 20:2062-79
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