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Evolution of placenta-specific gene expression: comparison of the equine and human gonadotropin alpha-subunit genes.
Abstract: Primate and equine species are thought to be unique among mammals in synthesizing placental gonadotropin glycoprotein hormones. Human chorionic gonadotropin (CG) and equine pregnant mare's serum gonadotropin (PMSG) are produced in placenta by the specific activation of a glycoprotein hormone alpha-subunit gene and a corresponding beta-subunit gene. The evolutionary mechanisms for the apparently independent acquisition of tissue specificity were investigated by cloning the 5' flanking region of the equine alpha-subunit gene and comparing the DNA elements and trans-acting factors involved in placental expression. We find that though the equine gene is expressed and induced by cAMP, it does not contain the elements known to confer tissue-specific expression to the human gene, the cAMP response element (CRE) and the trophoblast-specific element (TSE), nor does it bind to the trans-acting factors CREB and TSEB. Instead, an additional factor (alpha-ACT) is found which binds to the equine and human, but not the murine, alpha-subunit genes in a region between the positions of the CRE and TSE and confers cAMP responsiveness.
Publication Date: 1991-02-01 PubMed ID: 1710031DOI: 10.1210/mend-5-2-243Google Scholar: Lookup The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
- Comparative Study
- Journal Article
- Research Support
- Non-U.S. Gov't
- Research Support
- U.S. Gov't
- P.H.S.
Summary
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The study examines the different internal mechanisms used by primates (humans) and equines (horses) to produce hormones necessary for placental development during pregnancy. The results indicate that while both species employ the same hormone genes, the methods of activating those genes differ significantly.
Understanding Placental Hormones in Equine and Human
- The research studies the evolution of placenta-specific gene expression, focusing on hormone production in human and equine placentas. The hormones in question are human chorionic gonadotropin (CG) and equine pregnant mare’s serum gonadotropin (PMSG), which are produced in both species’ placentas.
- These hormones are produced by the activation of a specific alpha-subunit gene and a corresponding beta-subunit gene. The study seeks to understand the evolutionary mechanisms that led to the development of these genes’ tissue specificity.
Investigating Gene Activation Mechanisms
- Researchers performed this investigation by cloning the flanking region of the equine alpha-subunit gene and comparing its DNA elements and trans-acting factors. Trans-acting factors are proteins that bind to DNA and influence its replication and function.
- They found that the equine gene is activated and induced by cAMP, a derivative of adenosine triphosphate (ATP) that is used in many biological processes.
Discrepancies in Human and Equine Placental Gene Expression
- The equine gene, although induced by cAMP, does not contain the same elements as the human gene that confer tissue-specific expression. These elements in humans are the cAMP response element (CRE) and the trophoblast-specific element (TSE).
- Additionally, the equine gene does not bind to the trans-acting factors CREB and TSEB like the human gene does.
- Instead, researchers identified an additional factor (alpha-ACT) that binds to both equine and human hormones but not in murine (mouse) genes. This region is located in-between the positions of the CRE and TSE and activates the cAMP response in both species.
Implications of the Findings
- These findings suggest that the process for activating hormones necessary for placental development in pregnancy varies between species. While utilising the same hormones, equine and human species trigger these functions differently.
- Understanding these differences can provide further insight into reproductive processes and signify potential avenues for treating fertility issues or breeding strategies.
Cite This Article
APA
Steger DJ, Altschmied J, Büscher M, Mellon PL.
(1991).
Evolution of placenta-specific gene expression: comparison of the equine and human gonadotropin alpha-subunit genes.
Mol Endocrinol, 5(2), 243-255.
https://doi.org/10.1210/mend-5-2-243 Publication
Researcher Affiliations
- Salk Institute, La Jolla, California 92037.
MeSH Terms
- Animals
- Base Sequence
- Binding Sites
- Biological Evolution
- Choriocarcinoma
- Cyclic AMP / pharmacology
- Cyclic AMP Response Element-Binding Protein
- DNA-Binding Proteins / metabolism
- DNA-Binding Proteins / physiology
- Enhancer Elements, Genetic
- Female
- Gene Expression
- Glycoprotein Hormones, alpha Subunit / genetics
- Horses / genetics
- Humans
- Molecular Sequence Data
- Placenta / metabolism
- Pregnancy
- Promoter Regions, Genetic
- Regulatory Sequences, Nucleic Acid
- Sequence Homology, Nucleic Acid
- Transfection
- Tumor Cells, Cultured
- Uterine Neoplasms
Grant Funding
- R01 HD020377 / NICHD NIH HHS
- HD20377 / NICHD NIH HHS
- HD23818 / NICHD NIH HHS
Citations
This article has been cited 9 times.- Gupta R, Ezashi T, Roberts RM. Squelching of ETS2 transactivation by POU5F1 silences the human chorionic gonadotropin CGA subunit gene in human choriocarcinoma and embryonic stem cells. Mol Endocrinol 2012 May;26(5):859-72.
- Hamernik DL, Werth LA, Sundermann D, Zanella EL. The proximal 350 bp of 5'-flanking sequence of the human α-subunit glycoprotein hormone gene functions in the pituitary gland, but not the placenta, in transgenic mice. Endocrine 1996 Dec;5(3):257-63.
- Ezashi T, Ghosh D, Roberts RM. Repression of Ets-2-induced transactivation of the tau interferon promoter by Oct-4. Mol Cell Biol 2001 Dec;21(23):7883-91.
- LiCalsi C, Christophe S, Steger DJ, Buescher M, Fischer W, Mellon PL. AP-2 family members regulate basal and cAMP-induced expression of human chorionic gonadotropin. Nucleic Acids Res 2000 Feb 15;28(4):1036-43.
- Majumdar S, Irwin DM, Elsholtz HP. Selective constraints on the activation domain of transcription factor Pit-1. Proc Natl Acad Sci U S A 1996 Sep 17;93(19):10256-61.
- Lawson MA, Whyte DB, Mellon PL. GATA factors are essential for activity of the neuron-specific enhancer of the gonadotropin-releasing hormone gene. Mol Cell Biol 1996 Jul;16(7):3596-605.
- Steger DJ, Hecht JH, Mellon PL. GATA-binding proteins regulate the human gonadotropin alpha-subunit gene in the placenta and pituitary gland. Mol Cell Biol 1994 Aug;14(8):5592-602.
- Shida MM, Jackson-Grusby LL, Ross SR, Linzer DI. Placental-specific expression from the mouse placental lactogen II gene promoter. Proc Natl Acad Sci U S A 1992 May 1;89(9):3864-8.
- Horn F, Windle JJ, Barnhart KM, Mellon PL. Tissue-specific gene expression in the pituitary: the glycoprotein hormone alpha-subunit gene is regulated by a gonadotrope-specific protein. Mol Cell Biol 1992 May;12(5):2143-53.
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