Cyclic Adenosine 3′,5′-Monophosphate (cAMP) and cAMP Responsive Element-Binding Protein Are Involved in the Transcriptional Regulation of Gonadotropin-Releasing Hormone (GnRH) Receptor by GnRH and Mitogen-Activated Protein Kinase Signal Transduction Pathway in GGH3 Cells1 | Zendy

Guadalupe MayaNúñez | Zendy; P. Michael Conn | Zendy

Open Access

Cyclic Adenosine 3′,5′-Monophosphate (cAMP) and cAMP Responsive Element-Binding Protein Are Involved in the Transcriptional Regulation of Gonadotropin-Releasing Hormone (GnRH) Receptor by GnRH and Mitogen-Activated Protein Kinase Signal Transduction Pathway in GGH3 Cells1

Author(s) -

Guadalupe MayaNúñez,

P. Michael Conn

Publication year - 2001

Publication title -

biology of reproduction

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 1.366

H-Index - 180

eISSN - 1529-7268

pISSN - 0006-3363

DOI - 10.1095/biolreprod65.2.561

Subject(s) - creb , buserelin , protein kinase a , biology , creb1 , medicine , luciferase , endocrinology , mapk/erk pathway , response element , cyclic adenosine monophosphate , hormone response element , kinase , microbiology and biotechnology , agonist , receptor , transfection , promoter , transcription factor , gene expression , biochemistry , cancer , estrogen receptor , breast cancer , gene

Stimulation of mouse GnRH receptor promoter by a GnRH agonist (Buserelin), or by a cAMP analogue, significantly increased reporter (luciferase) activity. Overexpression of Raf-1, ERK1, or ERK2 partially blocked Buserelin-stimulated luciferase activity. In contrast, treatment with a mitogen-activated protein kinase (MAPK) kinase inhibitor (PD 98059) activated basal and Buserelin-stimulated luciferase activity in a dose-dependent manner. Transient transfection of the deleted cAMP response element expression vector followed by pretreatment with PD98059 prior to Buserelin stimulation showed that the transcriptional response was decreased compared to wild-type promoter. A gel-mobility shift assay using a probe containing the cAMP response element showed the presence of two specific protein-DNA complexes that contain one or more members of the cAMP responsive element-binding (CREB) protein family. These results suggest that cAMP and CREB participate in the GnRH activation of GnRH receptor promoter activity and that the MAPK cascade is involved in the negative regulation of basal and GnRH-stimulated GnRH receptor transcriptional activity.

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