The Role of Smads and AR in FSHbeta Gene Expression

Summary

Principal Investigator: Varykina G Thackray
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 Period: 2003-09-01 - 2006-08-31
more information: NIH RePORT

Top Publications

  1. pmc Activin regulates luteinizing hormone beta-subunit gene expression through Smad-binding and homeobox elements
    Djurdjica Coss
    Department of Reproductive Medicine, University of California San Diego, 9500 Gilman Drive, La Jolla, California 92093 0674, USA
    Mol Endocrinol 19:2610-23. 2005
  2. pmc Androgens, progestins, and glucocorticoids induce follicle-stimulating hormone beta-subunit gene expression at the level of the gonadotrope
    Varykina G Thackray
    Department of Reproductive Medicine, University of California at San Diego, 9500 Gilman Drive, La Jolla, California 92093 0674, USA
    Mol Endocrinol 20:2062-79. 2006
  3. pmc Activin and glucocorticoids synergistically activate follicle-stimulating hormone beta-subunit gene expression in the immortalized LbetaT2 gonadotrope cell line
    Shauna M McGillivray
    Department of Reproductive Medicine, University of California at San Diego, 9500 Gilman Drive, La Jolla, California 92093 0674, USA
    Endocrinology 148:762-73. 2007
  4. pmc Synergistic induction of follicle-stimulating hormone beta-subunit gene expression by gonadal steroid hormone receptors and Smad proteins
    Varykina G Thackray
    Department of Reproductive Medicine, Center for Reproductive Science and Medicine, University of California at San Diego, 9500 Gilman Drive, La Jolla, California 92093, USA
    Endocrinology 149:1091-102. 2008
  5. pmc Glucocorticoids induce human glycoprotein hormone alpha-subunit gene expression in the gonadotrope
    Ravid Sasson
    Department of Reproductive Medicine, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093 0674, USA
    Endocrinology 149:3643-55. 2008
  6. pmc Progesterone Inhibits basal and gonadotropin-releasing hormone induction of luteinizing hormone beta-subunit gene expression
    Varykina G Thackray
    Department of Reproductive Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093, USA
    Endocrinology 150:2395-403. 2009
  7. pmc Hormones in synergy: regulation of the pituitary gonadotropin genes
    Varykina G Thackray
    Department of Reproductive Medicine, Center for Reproductive Science and Medicine, University of California, San Diego, La Jolla, CA 92093 0674, USA
    Mol Cell Endocrinol 314:192-203. 2010

Detail Information

Publications7

  1. pmc Activin regulates luteinizing hormone beta-subunit gene expression through Smad-binding and homeobox elements
    Djurdjica Coss
    Department of Reproductive Medicine, University of California San Diego, 9500 Gilman Drive, La Jolla, California 92093 0674, USA
    Mol Endocrinol 19:2610-23. 2005
    ..Thus, activin induction of LHbeta gene expression requires a combination of several transcription factors, both basal and activin induced, as well as cooperation between multiple DNA elements...
  2. pmc Androgens, progestins, and glucocorticoids induce follicle-stimulating hormone beta-subunit gene expression at the level of the gonadotrope
    Varykina G Thackray
    Department of Reproductive Medicine, University of California at San Diego, 9500 Gilman Drive, La Jolla, California 92093 0674, USA
    Mol Endocrinol 20:2062-79. 2006
    ..Our data indicate that androgens, glucocorticoids, and progestins act via their receptors to directly activate FSHbeta gene expression in the pituitary gonadotrope...
  3. pmc Activin and glucocorticoids synergistically activate follicle-stimulating hormone beta-subunit gene expression in the immortalized LbetaT2 gonadotrope cell line
    Shauna M McGillivray
    Department of Reproductive Medicine, University of California at San Diego, 9500 Gilman Drive, La Jolla, California 92093 0674, USA
    Endocrinology 148:762-73. 2007
    ..Our studies provide the first evidence of a synergistic interaction between activin and glucocorticoids within the gonadotrope cell and demonstrate that this synergy can occur directly at the level of the mouse FSHbeta promoter...
  4. pmc Synergistic induction of follicle-stimulating hormone beta-subunit gene expression by gonadal steroid hormone receptors and Smad proteins
    Varykina G Thackray
    Department of Reproductive Medicine, Center for Reproductive Science and Medicine, University of California at San Diego, 9500 Gilman Drive, La Jolla, California 92093, USA
    Endocrinology 149:1091-102. 2008
    ....
  5. pmc Glucocorticoids induce human glycoprotein hormone alpha-subunit gene expression in the gonadotrope
    Ravid Sasson
    Department of Reproductive Medicine, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093 0674, USA
    Endocrinology 149:3643-55. 2008
    ....
  6. pmc Progesterone Inhibits basal and gonadotropin-releasing hormone induction of luteinizing hormone beta-subunit gene expression
    Varykina G Thackray
    Department of Reproductive Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093, USA
    Endocrinology 150:2395-403. 2009
    ..Altogether, our data indicate that progesterone feedback at the level of the pituitary gonadotrope is likely to play a key role in differential production of the gonadotropin genes...
  7. pmc Hormones in synergy: regulation of the pituitary gonadotropin genes
    Varykina G Thackray
    Department of Reproductive Medicine, Center for Reproductive Science and Medicine, University of California, San Diego, La Jolla, CA 92093 0674, USA
    Mol Cell Endocrinol 314:192-203. 2010
    ..We also discuss how recent technological advances will help identify additional factors involved in the differential hormonal regulation of LH and FSH...