scholarly journals Transcriptional Down-Regulation of Human Gonadotropin-Releasing Hormone (GnRH) Receptor Gene by GnRH: Role of Protein Kinase C and Activating Protein 1*

Endocrinology ◽  
2000 ◽  
Vol 141 (10) ◽  
pp. 3611-3622 ◽  
Author(s):  
Kwai Wa Cheng ◽  
Elly S. W. Ngan ◽  
Sung Keun Kang ◽  
Billy K. C. Chow ◽  
Peter C. K. Leung
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Receptor Gene ◽  
Gnrh Receptor ◽  
Gonadotropin Releasing Hormone ◽  
Down Regulation ◽  
Releasing Hormone ◽  
Kinase C

scholarly journals Absence of rapid desensitization of the mouse gonadotropin-releasing hormone receptor

1994 ◽  
Vol 300 (2) ◽  
pp. 299-302 ◽  
Author(s):  
J S Davidson ◽  
I K Wakefield ◽  
R P Millar
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Phorbol Ester ◽  
Inositol Phosphate ◽  
Gnrh Receptor ◽  
Gonadotropin Releasing Hormone ◽  
Gonadal Hormone ◽  
Releasing Hormone ◽  
Kinase C ◽  
Homologous Desensitization

Desensitization of gonadotropin release by the pituitary gland in response to gonadotropin-releasing hormone (GnRH) agonists has clinical applications in the treatment of gonadal-hormone-dependent disorders. We therefore investigated possible desensitization of inositol phosphate (IP) responses of GNRH receptors. No short-term homologous desensitization of the IP response to GnRH was observed in either alpha T3 gonadotrope cells line or GH3 cells transfected with GnRH receptor cDNA. The absence of homologous desensitization is unusual among G-protein-coupled receptors, and may be due to the absence of a C-terminal cytoplasmic tail, a unique feature of the GnRH receptor. Several potential protein kinase C phosphorylation sites which might mediate heterologous desensitization are present on the GnRH receptor. In both alpha T3 cells and GnRH-receptor-transfected Cos-1 cells, activation of protein kinase C by pretreatment with phorbol ester caused a 35-53% decrease in the IP response to GnRH. However, phorbol ester also inhibited guanosine 5′-[gamma-thio]triphosphate-stimulated IP production in permeabilized Cos-1 cells, suggesting that this inhibition is mediated at a post-receptor site.

scholarly journals Mechanism of gonadotropin-releasing hormone (GnRH)-I and -II-induced cell growth inhibition in ovarian cancer cells: role of the GnRH-I receptor and protein kinase C pathway

2006 ◽  
Vol 13 (1) ◽  
pp. 211-220 ◽  
Author(s):  
Ki-Yon Kim ◽  
Kyung-Chul Choi ◽  
Nelly Auersperg ◽  
Peter C K Leung
Keyword(s):  
Ovarian Cancer ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Cancer Cells ◽  
Gonadotropin Releasing Hormone ◽  
Ovarian Cancer Cells ◽  
Releasing Hormone ◽  
Proliferative Effect ◽  
Kinase C

In our previous studies, we demonstrated that ERK1/2 (extracellular signal-regulated protein kinase) and p38 MAPK (mitogen-activated protein kinase) are required for gonadotropin-releasing hormone (GnRH)-II-induced anti-proliferation of ovarian cancer cells. In the present study, we examined the role of the GnRH-I receptor, as well as the activation of protein kinase C (PKC), in the anti-proliferative effect induced by GnRH-I or II in ovarian cancer cells. Our results demonstrated that Antide, a GnRH-I antagonist, reversed the activation of ERK1/2 induced by GnRH-I or II and abolished the anti-proliferative effect of GnRH-I and II in ovarian cancer cells. Transfection of short-interfering RNA to abrogate the gene expression of the GnRH-I receptor reversed GnRH-I and II-induced anti-proliferation. These results indicate that GnRH-I or II induce anti-proliferation through the GnRH-I receptor in ovarian cancer cells. In addition, the activation of ERK1/2 by GnRH-I or II was mimicked by phorbol-12-myristate 13-acetate, a PKC activator. Pretreatment with GF109203X, an inhibitor of PKC, blocked GnRH-induced ERK1/2 activation and anti-proliferation. These results suggest that the activation of PKC is responsible for GnRH-induced ERK1/2 activation and anti-proliferation in ovarian cancer cells. Taken together, these results indicate that binding of GnRH-I and II to the GnRH-I receptor activates ERK1/2 through a PKC-dependent pathway and is essential for GnRH-induced anti-proliferation of ovarian cancer cells.

The 1990 James A. F. Stevenson Memorial Lecture. Gonadotropin-releasing hormone and its actions

1991 ◽  
Vol 69 (4) ◽  
pp. 445-458 ◽  
Author(s):  
Tim D. Braden ◽  
P. Michael Conn
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Gonadotropin Releasing Hormone ◽  
Extracellular Calcium ◽  
Receptor Protein ◽  
Memorial Lecture ◽  
Down Regulation ◽  
Releasing Hormone ◽  
Gnrh Receptors ◽  
Kinase C

Gonadotropin-releasing hormone (GnRH) stimulates the release and biosynthesis of gonadotropins, luteinizing hormone, and follicle-stimulating hormone from the pituitary gland. Additionally, GnRH regulates the number of its own receptors on pituitary gonadotropes causing both up- and down-regulation of receptors as well as biosynthesis of GnRH receptors. After exposure to GnRH, gonadotropes become desensitized to further stimulation by GnRH. The mechanisms through which these actions of GnRH are mediated appear to differ. Effects dependent upon extracellular calcium include gonadotropin biosynthesis and release as well as up-regulation of GnRH receptors. Additional actions of GnRH, such as down-regulation of receptors, biosynthesis of receptors, and desensitization, appear to be independent of extracellular calcium. Subsequent studies have ascribed roles for calmodulin and protein kinase C in mediating specific effects of GnRH.Key words: pituitary, gonadotropin-releasing hormone, receptor, protein kinase C, calmodulin.

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