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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
GnRH-mediated DAN production regulates the transcription of the GnRH receptor in gonadotrope cells
NeuroMolecular Medicine, Volume 9, No. 3, Year 2007
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Description
The primary function of gonadotropin-releasing hormone (GnRH) is the regulation of pituitary gonadotropin hormone gene transcription, biosynthesis and release. These effects are mediated through intracellular mobilization of Ca2+ and activation of PKC isoforms and MAP kinases. We show here that DAN (differential screening-selected gene aberrative in neuroblastoma) which is a secreted bone morphogenic protein (BMP) antagonist belonging to the TGFβ protein superfamily, is controlled by GnRH in murine gonadotrope cells. Acute GnRH stimulation induced a rapid, 27-fold, elevation of DAN mRNA, accompanied by an approximate 3-fold increase in the amount of mature DAN glycoprotein in the cell cytoplasm and in DAN secretion into the culture medium. Incubation of LβT2 cells in DAN-containing medium altered the levels of a number of cellular proteins. Two of these were identified as the steroidogenic acute regulatory protein (StAR) and the actin-related protein 2/3 complex subunits 2 (p34-ARC) which are primarily involved in steroidogenesis and cytoskeleton remodelling, respectively. DAN caused an approximate 2-fold specific elevation in the cytoplasmic levels of both these proteins in LβT2 cells. We further tested the effects of DAN on classical GnRH effects viz. gonadotropin and GnRH receptor gene expression. Co-transfection of LβT2 cells with DAN and gonadotropin subunit promoter luciferase reporter genes had no effect on GnRH stimulation of αGSU and LHβ or on the additive GnRH and activin induction of FSHβ subunit transcription. However, co-transfection of DAN markedly inhibited the synergistic activation of GnRH and activin on GnRH receptor gene expression thus implicating DAN as a novel autocrine/paracrine factor that modulates GnRH function in pituitary gonadotropes. © Humana Press Inc. 2007.
Authors & Co-Authors
López de Maturana, Rakel
United Kingdom, Edinburgh
Mrc Human Reproductive Sciences Unit
United Kingdom, Edinburgh
Ardana
Spain, Leioa
Universidad Del Pais Vasco
Millar, Robert P.
United Kingdom, Edinburgh
Mrc Human Reproductive Sciences Unit
Davidson, Lindsay
United Kingdom, Edinburgh
Mrc Human Reproductive Sciences Unit
United Kingdom, Dundee
University of Dundee
Pawson, Adam J.
United Kingdom, Edinburgh
Mrc Human Reproductive Sciences Unit
Nicol, Moira R.
United Kingdom, Edinburgh
Mrc Centre for Reproductive Health
Mason, James Ian
United Kingdom, Edinburgh
Mrc Centre for Reproductive Health
Barran, Perdita E.
United Kingdom, Edinburgh
The University of Edinburgh
Naor, Zvi
United Kingdom, Edinburgh
Mrc Human Reproductive Sciences Unit
Israel, Tel Aviv-yafo
Tel Aviv University
Maudsley, S. R.
United Kingdom, Edinburgh
Mrc Human Reproductive Sciences Unit
United States, Baltimore
Nia Gerontology Research Center
Statistics
Citations: 15
Authors: 9
Affiliations: 8
Identifiers
Doi:
10.1007/s12017-007-8004-z
ISSN:
15351084
Research Areas
Genetics And Genomics