scholarly journals Regulation of Porcine Pituitary Glycoprotein Hormone Alpha Subunit Gene with LIM-Homeobox Transcription Factor Lhx3

2009 ◽  
Vol 55 (4) ◽  
pp. 425-432 ◽  
Author(s):  
Takao SUSA ◽  
Akio ISHIKAWA ◽  
Takako KATO ◽  
Michie NAKAYAMA ◽  
Kousuke KITAHARA ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Alpha Subunit ◽  
Subunit Gene ◽  
Glycoprotein Hormone ◽  
Homeobox Transcription Factor

Expression of the glycoprotein hormone alpha-subunit gene in the placenta requires a functional cyclic AMP response element, whereas a different cis-acting element mediates pituitary-specific expression

1989 ◽  
Vol 9 (11) ◽  
pp. 5113-5122
Author(s):  
J A Bokar ◽  
R A Keri ◽  
T A Farmerie ◽  
R A Fenstermaker ◽  
B Andersen ◽  
...  
Keyword(s):  
Cyclic Amp ◽  
Transgenic Mice ◽  
Regulatory Region ◽  
Alpha Subunit ◽  
Subunit Gene ◽  
Glycoprotein Hormone ◽  
Specific Expression ◽  
Response Element ◽  
Cyclic Amp Response Element ◽  
Choriocarcinoma Cells

The single-copy gene encoding the alpha subunit of glycoprotein hormones is expressed in the pituitaries of all mammals and in the placentas of only primates and horses. We have systematically analyzed the promoter-regulatory elements of the human and bovine alpha-subunit genes to elucidate the molecular mechanisms underlying their divergent patterns of tissue-specific expression. This analysis entailed the use of transient expression assays in a chorionic gonadotropin-secreting human choriocarcinoma cell line, protein-DNA binding assays, and expression of chimeric forms of human or bovine alpha subunit genes in transgenic mice. From the results, we conclude that placental expression of the human alpha-subunit gene requires a functional cyclic AMP response element (CRE) that is present as a tandem repeat in the promoter-regulatory region. In contrast, the promoter-regulatory region of the bovine alpha-subunit gene, as well as of the rat and mouse genes, was found to contain a single CRE homolog that differed from its human counterpart by a single nucleotide. This difference substantially reduced the binding affinity of the bovine CRE homolog for the nuclear protein that bound to the human alpha CRE and thereby rendered the bovine alpha-subunit promoter inactive in human choriocarcinoma cells. However, conversion of the bovine alpha CRE homolog to an authentic alpha CRE restored activity to the bovine alpha-subunit promoter in choriocarcinoma cells. Similarly, a human but not a bovine alpha transgene was expressed in placenta in transgenic mice. Thus, placenta-specific expression of the human alpha-subunit gene may be the consequence of the recent evolution of a functional CRE. Expression of the human alpha transgene in mouse placenta further suggests that evolution of placenta-specific trans-acting factors preceded the appearance of this element. Finally, in contrast to their divergent patterns of placental expression, both the human and bovine alpha-subunit transgenes were expressed in mouse pituitary, indicating differences in the composition of the enhancers required for pituitary- and placenta-specific expression.

scholarly journals Cyclic AMP regulation of the human glycoprotein hormone alpha-subunit gene is mediated by an 18-base-pair element.

1987 ◽  
Vol 84 (8) ◽  
pp. 2198-2202 ◽  
Author(s):  
B. J. Silver ◽  
J. A. Bokar ◽  
J. B. Virgin ◽  
E. A. Vallen ◽  
A. Milsted ◽  
...  
Keyword(s):  
Cyclic Amp ◽  
Base Pair ◽  
Alpha Subunit ◽  
Subunit Gene ◽  
Glycoprotein Hormone

scholarly journals A role for mitogen-activated protein kinase in mediating activation of the glycoprotein hormone alpha-subunit promoter by gonadotropin-releasing hormone.

1995 ◽  
Vol 15 (7) ◽  
pp. 3531-3539 ◽  
Author(s):  
M S Roberson ◽  
A Misra-Press ◽  
M E Laurance ◽  
P J Stork ◽  
R A Maurer
Keyword(s):  
Protein Kinase ◽  
Expression Vector ◽  
Gonadotropin Releasing Hormone ◽  
Mapk Cascade ◽  
Mitogen Activated Protein Kinase ◽  
Alpha Subunit ◽  
Subunit Gene ◽  
Glycoprotein Hormone ◽  
Mitogen Activated Protein ◽  
Stimulation Of

Gonadotropin-releasing hormone (GnRH) interacts with a G protein-coupled receptor and increases the transcription of the glycoprotein hormone alpha-subunit gene. We have explored the possibility that mitogen-activated protein kinase (MAPK) plays a role in mediating GnRH effects on transcription. Activation of the MAPK cascade by an expression vector for a constitutively active form of the Raf-1 kinase led to stimulation of the alpha-subunit promoter in a concentration-dependent manner. GnRH treatment was found to increase the phosphorylation of tyrosine residues of MAPK and to increase MAPK activity, as determined by an immune complex kinase assay. A reporter gene assay using the MAPK-responsive, carboxy-terminal domain of the Elk1 transcription factor was also consistent with GnRH-induced activation of MAPK. Interference with the MAPK pathway by expression vectors for kinase-defective MAPKs or vectors encoding MAPK phosphatases reduced the transcription-stimulating effects of GnRH. The DNA sequences which are required for responses to GnRH include an Ets factor-binding site. An expression vector for a dominant negative form of Ets-2 was able to reduce GnRH effects on expression of the alpha-subunit gene. These findings provide evidence that GnRH treatment leads to activation of the MAPK cascade in gonadotropes and that activation of MAPK contributes to stimulation of the alpha-subunit promoter. It is likely that an Ets factor serves as a downstream transcriptional effector of MAPK in this system.

scholarly journals Tissue-specific gene expression in the pituitary: the glycoprotein hormone alpha-subunit gene is regulated by a gonadotrope-specific protein.

1992 ◽  
Vol 12 (5) ◽  
pp. 2143-2153 ◽  
Author(s):  
F Horn ◽  
J J Windle ◽  
K M Barnhart ◽  
P L Mellon
Keyword(s):  
Molecular Mechanisms ◽  
Regulatory Element ◽  
Alpha Subunit ◽  
Specific Factor ◽  
Specific Gene ◽  
Homeodomain Protein ◽  
Subunit Gene ◽  
Glycoprotein Hormone ◽  
Specific Expression ◽  
Tissue Specific

The molecular mechanisms for the development of multiple distinct endocrine cell types in the anterior pituitary have been an area of intensive investigation. Though the homeodomain protein Pit-1/GHF-1 is known to be involved in differentiation of the somatotrope and lactotrope lineages, which produce growth hormone and prolactin, respectively, little is known of the transcriptional regulators important for the gonadotrope cell lineage, which produces the glycoprotein hormones luteinizing hormone and follicle-stimulating hormone. Using transgenic mice and transfection into a novel gonadotrope lineage cell line, we have identified a regulatory element that confers gonadotrope-specific expression to the glycoprotein hormone alpha-subunit gene. A tissue-specific factor that binds to this element is purified and characterized as a 54-kDa protein which is present uniquely in cells of the gonadotrope lineage and is not Pit-1/GHF-1. The human and equine alpha-subunit genes are also expressed in placental cells. However, the previously characterized placental transcription factors designated TSEB and alpha-ACT are not found in the pituitary gonadotrope cells, indicating that independent mechanisms confer expression of these genes in the two different tissues.

Sign in / Sign up

Export Citation Format

Share Document