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Synergistic Effects in Gene Regualtion by Human SRY and Androgen Receptor

Troyer, Samuel A.
http://rave.ohiolink.edu/etdc/view?acc_num=akron1321033166

Abstract Details

2011, Master of Science, University of Akron, Biology.
Hypertension is a condition that affects one in three people in the United States and contributes to many health problems involving the cardiovascular system. SRY, a Y chromosome gene, is a member of the SOX transcription factor family and shows regulatory effects on genes that influence blood pressure. SRY is proposed to regulate the renin-angiotensin system and the sympathetic nervous system in a way that leads to an increase in blood pressure. In the spontaneously hypertensive rat, Sry is a candidate gene for the blood pressure increase, in which a full functioning androgen receptor is also required. Direct protein interaction is known to occur between SRY and androgen receptor as well, allowing for the potential of synergistic effects in gene regulation. To test this hypothesis, luciferase promoter constructs containing response elements for both SRY and androgen receptor were transfected into CHO cells along with SRY and androgen receptor expression vectors. Transfections were done in the presence of 100nM testosterone and the absence of testosterone. In the presence of testosterone a greater effect in regulation was seen when both SRY and androgen receptor were present compared to the effect of either alone. Through computer modeling and molecular dynamic simulations a recruitment mechanism is postulated in which the carboxy terminal extension (CTE) of androgen receptor recruits SRY to the DNA via the HMG-box of SRY. This data supports the hypothesis that SRY and androgen receptor act synergistically in gene regulation in the presence of testosterone. It may also shed light on the reason that, during reproductive years, males are more likely to develop hypertension than females. The insight given through the molecular dynamic simulations will help with developing a further understanding of the mechanism behind these effects and may provide new ideas for drug targets.
Amy Milsted, Dr. (Advisor)
Monte Turner, Dr. (Committee Member)
Rolando JJ Ramirez, Dr. (Committee Member)
75 p.
Molecular Biology
SRY; Androgen Receptor; SOX; Hypertension; Samuel Troyer

Recommended Citations

Citations

  • Troyer, S. A. (2011). Synergistic Effects in Gene Regualtion by Human SRY and Androgen Receptor [Master's thesis, University of Akron]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=akron1321033166

    APA Style (7th edition)

  • Troyer, Samuel. Synergistic Effects in Gene Regualtion by Human SRY and Androgen Receptor. 2011. University of Akron, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=akron1321033166.

    MLA Style (8th edition)

  • Troyer, Samuel. "Synergistic Effects in Gene Regualtion by Human SRY and Androgen Receptor." Master's thesis, University of Akron, 2011. http://rave.ohiolink.edu/etdc/view?acc_num=akron1321033166

    Chicago Manual of Style (17th edition)

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© 2011, all rights reserved.
This open access ETD is published by University of Akron and OhioLINK.