Strategies for construction of luteinizing hormone beta subunit analogs with carboxyl terminal extensions in non-primate, non-equid mammalian species.
Abstract: Chorionic gonadotropins (CG) are unique because they have a carboxyl terminal peptide (CTP) extension on their beta subunits that prolongs circulatory survival. CGbeta genes from the human being and horse have evolved from ancestral luteinizing hormone (LH) beta genes by different pathways that involve deletions that change the reading frames and yield a CTP. Here we further review our previous analysis, aimed at determining whether LHbeta genes in non-primate, non-equid species inherently possess DNA sequences that encode CTP-like domains. In multiple mammalian species, simple frame-shift mutations using either the human or equine CGbeta gene as a model can be used to construct LHbeta analogs with putative CTP domains. Furthermore, DNA sequences from mammalian LHbeta genes can be aligned to maximize similarity with CGbeta genes in order to devise more refined strategies for construction of CTP-bearing LHbeta analogs as exemplified in the bovine case. Thus, mammalian LHbeta genes have DNA sequences that can be potentially expressed in order to construct CTP-bearing glycoprotein hormone analogs.
Publication Date: 2006-11-07 PubMed ID: 17092639DOI: 10.1016/j.mce.2005.11.054Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The research analyses the DNA of non-primate, non-equid mammalian species to explore if they inherently possess sequences that encode carboxyl terminal peptide-like domains, which are unique to chorionic gonadotropins and contribute to prolonged circulatory survival. The study concludes that these DNA sequences can potentially be expressed to construct glycoprotein hormone analogs with CTP.
Understanding Chorionic Gonadotropins
- The article centers around Chorionic gonadotropins (CG), a type of hormone unique due to their carboxyl terminal peptide (CTP) extension on their beta subunits. This CTP is responsible for the prolonged circulatory survival of the hormones.
- The creation of luteinizing hormone (LH) beta subunit analogs with carboxyl terminal extensions is the main objective of this study.
- CGbeta genes derived from humans and horses have evolved from their ancestral LH beta genes. This evolution took place via different pathways, which mostly involved deletions that changed the genetic reading frames and resulted in the CTP.
Study Analysis and Findings
- The research focuses on identifying whether LHbeta genes in non-primate, non-equid species contain DNA sequences that can encode CTP-like domains.
- Through analysis of multiple mammalian species, the researchers discovered that simple frame-shift mutations, modeled after human or equine CGbeta genes, can be used to construct LHbeta analogs that contain potential CTP domains.
- It was further determined that DNA sequences from mammalian LHbeta genes can be aligned to increase similarity with CGbeta genes. This alignment strategy provides a more refined approach to construct CTP-bearing LHbeta analogs, as demonstrated through bovine examples.
Significance and Conclusion of the Research
- The research concludes that mammalian LHbeta genes contain DNA sequences that can potentially be expressed to create CTP-bearing glycoprotein hormone analogs.
- This research can have significant relevance in hormone studies. By identifying the presence of CTP domains, it helps to further our understanding of the function and prolongation of circulatory survival in hormones.
- The ability to create LHbeta analogs that bear CTP domains might contribute to new strategies for the treatment of hormone-related disorders in non-primate and non-equid mammals.
Cite This Article
APA
Ben-Menahem D, Grotjan HE.
(2006).
Strategies for construction of luteinizing hormone beta subunit analogs with carboxyl terminal extensions in non-primate, non-equid mammalian species.
Mol Cell Endocrinol, 260-262, 205-211.
https://doi.org/10.1016/j.mce.2005.11.054 Publication
Researcher Affiliations
- Department of Clinical Pharmacology, Ben-Gurion University, Faculty of Health Sciences, P.O.B. 653, Beer-Sheva 84105, Israel. dbm@bgu.ac.il
MeSH Terms
- Amino Acid Sequence
- Animals
- Base Sequence
- Chorionic Gonadotropin, beta Subunit, Human / chemistry
- Chorionic Gonadotropin, beta Subunit, Human / genetics
- Evolution, Molecular
- Frameshift Mutation / genetics
- Horses
- Humans
- Luteinizing Hormone / analogs & derivatives
- Luteinizing Hormone / chemistry
- Luteinizing Hormone / genetics
- Mammals / genetics
- Mammals / metabolism
- Models, Molecular
- Molecular Sequence Data
- Peptides / chemistry
- Peptides / genetics
- Polyadenylation
- Primates
- Protein Structure, Tertiary
- Ruminants
- Sequence Homology
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