Research ExplorerPublicationsGonadotropin-mediated regulation of the murine VEGF expressi...

Gonadotropin-mediated regulation of the murine VEGF expression in MA-10 Leydig cells

Standard

Gonadotropin-mediated regulation of the murine VEGF expression in MA-10 Leydig cells. / Schwarzenbach, Heidi; Chakrabarti, Gopa; Paust, Hans Joachim; Mukhopadhyay, Amal K.

In: J ANDROL, Vol. 25, No. 1, 2003, p. 128-39.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Schwarzenbach, H, Chakrabarti, G, Paust, HJ & Mukhopadhyay, AK 2003, 'Gonadotropin-mediated regulation of the murine VEGF expression in MA-10 Leydig cells', J ANDROL, vol. 25, no. 1, pp. 128-39.

APA

Schwarzenbach, H., Chakrabarti, G., Paust, H. J., & Mukhopadhyay, A. K. (2003). Gonadotropin-mediated regulation of the murine VEGF expression in MA-10 Leydig cells. J ANDROL, 25(1), 128-39.

Vancouver

Schwarzenbach H, Chakrabarti G, Paust HJ, Mukhopadhyay AK. Gonadotropin-mediated regulation of the murine VEGF expression in MA-10 Leydig cells. J ANDROL. 2003;25(1):128-39.

Bibtex

@article{f7fbf42a89d04114a5a7be2b769fc03a,
title = "Gonadotropin-mediated regulation of the murine VEGF expression in MA-10 Leydig cells",
abstract = "Presence of vascular endothelial growth factor (VEGF) is not only limited to cells directly involved in angiogenesis but has also been demonstrated in steroidogenic cells like testicular Leydig cells. Because Leydig cells are subjected to regulation by gonadotropic hormones and produce steroid hormones, we have investigated here the effects of human chorionic gonadotropin (hCG) or steroid hormones on VEGF expression in cultured mouse tumor Leydig cells (MA-10 cells) and have then analyzed the underlying molecular mechanisms. Northern blot analysis and enzyme-linked immunosorbent assays revealed increases in VEGF mRNA and protein levels, respectively, over 3-20 hours in MA-10 cells after stimulation with hCG or 8-Br-cAMP. Although MA-10 cells lack the classical progesterone receptor, progesterone was able to stimulate VEGF expression. Promoter analyses and antibody supershift experiments suggested that the proximal region is able to constitutively bind the transcription factors Sp1 and Sp3. Mutations of 2 potential Sp1 binding sites in the proximal region showed the requirement of these motifs for stimulation of VEGF by hCG and 8-Br-cAMP. The distal cytosine-rich sequence interacts with so far-unidentified faster migrating factors. Following stimulation with hCG or 8-Br-cAMP, the binding of these proteins was increased in the complexes formed in the proximal and distal regions. VEGF expression in Leydig cells is regulated by gonadotropin via a cAMP-dependent mechanism, and the transcription factors Sp1 and Sp3 appear to be involved in the activation of the promoter. Progesterone also appears to play a role in the regulation of VEGF, acting presumably via a nonconventional receptor that remains to be characterized yet.",
keywords = "8-Bromo Cyclic Adenosine Monophosphate, Animals, Capillary Permeability, Cell Line, Tumor, Chorionic Gonadotropin, Cytosine, DNA-Binding Proteins, Gene Expression, Leydig Cell Tumor, Leydig Cells, Male, Mice, Progesterone, Promoter Regions, Genetic, RNA, Messenger, Signal Transduction, Sp1 Transcription Factor, Sp3 Transcription Factor, Testicular Neoplasms, Transcription Factors, Vascular Endothelial Growth Factor A",
author = "Heidi Schwarzenbach and Gopa Chakrabarti and Paust, {Hans Joachim} and Mukhopadhyay, {Amal K}",
year = "2003",
language = "English",
volume = "25",
pages = "128--39",
number = "1",

}

RIS

TY - JOUR

T1 - Gonadotropin-mediated regulation of the murine VEGF expression in MA-10 Leydig cells

AU - Schwarzenbach, Heidi

AU - Chakrabarti, Gopa

AU - Paust, Hans Joachim

AU - Mukhopadhyay, Amal K

PY - 2003

Y1 - 2003

N2 - Presence of vascular endothelial growth factor (VEGF) is not only limited to cells directly involved in angiogenesis but has also been demonstrated in steroidogenic cells like testicular Leydig cells. Because Leydig cells are subjected to regulation by gonadotropic hormones and produce steroid hormones, we have investigated here the effects of human chorionic gonadotropin (hCG) or steroid hormones on VEGF expression in cultured mouse tumor Leydig cells (MA-10 cells) and have then analyzed the underlying molecular mechanisms. Northern blot analysis and enzyme-linked immunosorbent assays revealed increases in VEGF mRNA and protein levels, respectively, over 3-20 hours in MA-10 cells after stimulation with hCG or 8-Br-cAMP. Although MA-10 cells lack the classical progesterone receptor, progesterone was able to stimulate VEGF expression. Promoter analyses and antibody supershift experiments suggested that the proximal region is able to constitutively bind the transcription factors Sp1 and Sp3. Mutations of 2 potential Sp1 binding sites in the proximal region showed the requirement of these motifs for stimulation of VEGF by hCG and 8-Br-cAMP. The distal cytosine-rich sequence interacts with so far-unidentified faster migrating factors. Following stimulation with hCG or 8-Br-cAMP, the binding of these proteins was increased in the complexes formed in the proximal and distal regions. VEGF expression in Leydig cells is regulated by gonadotropin via a cAMP-dependent mechanism, and the transcription factors Sp1 and Sp3 appear to be involved in the activation of the promoter. Progesterone also appears to play a role in the regulation of VEGF, acting presumably via a nonconventional receptor that remains to be characterized yet.

AB - Presence of vascular endothelial growth factor (VEGF) is not only limited to cells directly involved in angiogenesis but has also been demonstrated in steroidogenic cells like testicular Leydig cells. Because Leydig cells are subjected to regulation by gonadotropic hormones and produce steroid hormones, we have investigated here the effects of human chorionic gonadotropin (hCG) or steroid hormones on VEGF expression in cultured mouse tumor Leydig cells (MA-10 cells) and have then analyzed the underlying molecular mechanisms. Northern blot analysis and enzyme-linked immunosorbent assays revealed increases in VEGF mRNA and protein levels, respectively, over 3-20 hours in MA-10 cells after stimulation with hCG or 8-Br-cAMP. Although MA-10 cells lack the classical progesterone receptor, progesterone was able to stimulate VEGF expression. Promoter analyses and antibody supershift experiments suggested that the proximal region is able to constitutively bind the transcription factors Sp1 and Sp3. Mutations of 2 potential Sp1 binding sites in the proximal region showed the requirement of these motifs for stimulation of VEGF by hCG and 8-Br-cAMP. The distal cytosine-rich sequence interacts with so far-unidentified faster migrating factors. Following stimulation with hCG or 8-Br-cAMP, the binding of these proteins was increased in the complexes formed in the proximal and distal regions. VEGF expression in Leydig cells is regulated by gonadotropin via a cAMP-dependent mechanism, and the transcription factors Sp1 and Sp3 appear to be involved in the activation of the promoter. Progesterone also appears to play a role in the regulation of VEGF, acting presumably via a nonconventional receptor that remains to be characterized yet.

KW - 8-Bromo Cyclic Adenosine Monophosphate

KW - Animals

KW - Capillary Permeability

KW - Cell Line, Tumor

KW - Chorionic Gonadotropin

KW - Cytosine

KW - DNA-Binding Proteins

KW - Gene Expression

KW - Leydig Cell Tumor

KW - Leydig Cells

KW - Male

KW - Mice

KW - Progesterone

KW - Promoter Regions, Genetic

KW - RNA, Messenger

KW - Signal Transduction

KW - Sp1 Transcription Factor

KW - Sp3 Transcription Factor

KW - Testicular Neoplasms

KW - Transcription Factors

KW - Vascular Endothelial Growth Factor A

M3 - SCORING: Journal article

C2 - 14662796

VL - 25

SP - 128

EP - 139

IS - 1

ER -