A single gene encodes the beta-subunits of equine luteinizing hormone and chorionic gonadotropin.
Abstract: Equine (e) CG and LH beta-subunits have identical amino acid sequences, including an extended carboxyl-terminal peptide (CTP). This suggests that unlike the corresponding human genes, the beta-subunits of eCG and eLH may be encoded by a single gene and share a common proximal promotor region. To explore this, we isolated and characterized the eLH/CG beta gene(s). Data from Southern analyses suggest that the eCG beta and eLH beta subunits are products of the same single copy gene (eLH/CG beta). Overlapping fragments of the eLH/CG beta gene and cDNA were amplified from equine genomic DNA and pituitary gland mRNA by the polymerase chain reaction, cloned, and sequenced. The eLH/CG beta gene spans less than 1.2 kilobase-pairs and has three exons that translate a CTP-containing polypeptide identical in sequence to that previously reported for the mature equine protein. There is, however, little amino acid homology shown between the CTP of human or equine CG beta subunit. In addition, unlike the human genes, the same TATAA-like element appears to be involved in directing initiation of transcription of the eLH/CG beta gene in placenta and anterior pituitary. Based upon these differences, we suggest that the CG beta genes evolved independently in humans and equids and that different mechanisms are involved in their patterns of placenta-specific expression.
Publication Date: 1992-06-01 PubMed ID: 1379674DOI: 10.1210/mend.6.6.1379674Google Scholar: Lookup
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- Comparative Study
- Journal Article
- Research Support
- Non-U.S. Gov't
- Research Support
- U.S. Gov't
- Non-P.H.S.
- Research Support
- U.S. Gov't
- P.H.S.
Summary
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This research article findings highlight that the beta-subunits of equine luteinizing hormone (eLH) and chorionic gonadotropin (eCG) are encoded by the same gene, which is different from the way that human versions of these hormones are encoded. In addition, it suggests that different mechanisms are involved in their patterns of placenta-specific expression in humans and horses.
Objective and Approach of the Research
- The primary objective of this study was to understand if the beta-subunits of equine luteinizing hormone (eLH) and equine chorionic gonadotropin (eCG) are encoded by a single gene and share a common promotor region, which would be different from the corresponding human genes. To achieve this, the research team isolated and characterized the eLH/CG beta gene.
- This investigation involved amplifying overlapping fragments of the eLH/CG beta gene and complementary DNA from equine genomic DNA and pituitary gland mRNA, which were then cloned and sequenced.
Key Findings of the Study
- The analysis determined that the beta-subunits of eCG and eLH are indeed products of the same single copy gene, referred to as the eLH/CG beta.
- The eLH/CG beta gene spans less than 1.2 kilobase-pairs and consists of three exons that encode a polypeptide which contains a carboxyl-terminal peptide.
- However, there is limited homology in terms of amino acid between the carboxyl-terminal peptide of human and equine CG beta subunit.
- Another critical difference between the human and equine genes is that the same TATAA-like element is involved in initiating transcription of the eLH/CG beta gene in both the placenta and anterior pituitary in horses, unlike in humans.
Implications of the Research
- Bearing in mind these findings, the researchers proposed that the CG beta genes in humans and equids have evolved independently.
- They infer that different mechanisms are at play in their patterns of placenta-specific expression in equids and humans.
- This research may have significant implications in the understanding of hormone synthesis in different species and could potentially influence treatment approaches in veterinary medicine.
Cite This Article
APA
Sherman GB, Wolfe MW, Farmerie TA, Clay CM, Threadgill DS, Sharp DC, Nilson JH.
(1992).
A single gene encodes the beta-subunits of equine luteinizing hormone and chorionic gonadotropin.
Mol Endocrinol, 6(6), 951-959.
https://doi.org/10.1210/mend.6.6.1379674 Publication
Researcher Affiliations
- Department of Pharmacology, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106.
MeSH Terms
- Amino Acid Sequence
- Animals
- Base Sequence
- Chorionic Gonadotropin / genetics
- Chorionic Gonadotropin, beta Subunit, Human
- Gene Expression Regulation
- Genes
- Horses / genetics
- Humans
- Luteinizing Hormone / genetics
- Molecular Sequence Data
- Organ Specificity
- Peptide Fragments / genetics
- Phylogeny
- Pituitary Gland, Anterior / metabolism
- Placenta / metabolism
- Primates / genetics
- Primates / metabolism
- Promoter Regions, Genetic
- RNA, Messenger / biosynthesis
- Sequence Homology, Nucleic Acid
- Species Specificity
- TATA Box
- Transcription, Genetic
Grant Funding
- DK-43039 / NIDDK NIH HHS
- HD-07138 / NICHD NIH HHS
- P30-CA-43730 / NCI NIH HHS
Citations
This article has been cited 16 times.- Byambaragchaa M, Choi SH, Joo HE, Kim SG, Kim YJ, Park GE, Kang MH, Min KS. Specific Biological Activity of Equine Chorionic Gonadotropin (eCG) Glycosylation Sites in Cells Expressing Equine Luteinizing Hormone/CG (eLH/CG) Receptor.. Dev Reprod 2021 Dec;25(4):199-211.
- Antczak DF, Allen WRT. Placentation in Equids.. Adv Anat Embryol Cell Biol 2021;234:91-128.
- Querat B. Unconventional Actions of Glycoprotein Hormone Subunits: A Comprehensive Review.. Front Endocrinol (Lausanne) 2021;12:731966.
- Lee SY, Byambaragchaa M, Choi SH, Kang HJ, Kang MH, Min KS. Roles of N-linked and O-linked glycosylation sites in the activity of equine chorionic gonadotropin in cells expressing rat luteinizing hormone/chorionic gonadotropin receptor and follicle-stimulating hormone receptor.. BMC Biotechnol 2021 Sep 5;21(1):52.
- Byambaragchaa M, Park A, Gil SJ, Lee HW, Ko YJ, Choi SH, Kang MH, Min KS. Luteinizing hormone-like and follicle-stimulating hormone-like activities of equine chorionic gonadotropin β-subunit mutants in cells expressing rat luteinizing hormone/chorionic gonadotropin receptor and rat follicle-stimulating hormone receptor.. Anim Cells Syst (Seoul) 2021;25(3):171-181.
- Min KS, Park JJ, Lee SY, Byambaragchaa M, Kang MH. Comparative gene expression profiling of mouse ovaries upon stimulation with natural equine chorionic gonadotropin (N-eCG) and tethered recombinant-eCG (R-eCG).. BMC Biotechnol 2020 Nov 11;20(1):59.
- Wang W, La Y, Li F, Liu S, Pan X, Li C, Zhang X. Molecular Characterization and Expression Profiles of the Ovine LHβ Gene and Its Association with Litter Size in Chinese Indigenous Small-Tailed Han Sheep.. Animals (Basel) 2020 Mar 10;10(3).
- Kalwar Q, Chu M, Ahmad AA, Ding X, Wu X, Bao P, Yan P. Morphometric Evaluation of Spermatogenic Cells and Seminiferous Tubules and Exploration of Luteinizing Hormone Beta Polypeptide in Testis of Datong Yak.. Animals (Basel) 2019 Dec 30;10(1).
- Min KS, Park JJ, Byambaragchaa M, Kang MH. Characterization of tethered equine chorionic gonadotropin and its deglycosylated mutants by ovulation stimulation in mice.. BMC Biotechnol 2019 Aug 13;19(1):60.
- Kara E, Dupuy L, Bouillon C, Casteret S, Maurel MC. Modulation of Gonadotropins Activity by Antibodies.. Front Endocrinol (Lausanne) 2019;10:15.
- Read JE, Cabrera-Sharp V, Kitscha P, Cartwright JE, King PJ, Fowkes RC, de Mestre AM. Glial Cells Missing 1 Regulates Equine Chorionic Gonadotrophin Beta Subunit via Binding to the Proximal Promoter.. Front Endocrinol (Lausanne) 2018;9:195.
- Bhardwaj A, Nayan V, Sharma P, Kumar S, Pal Y, Singh J. Molecular characterization, modeling, in silico analysis of equine pituitary gonadotropin alpha subunit and docking interaction studies with ganirelix.. In Silico Pharmacol 2016 Dec;5(1):5.
- Cohen L, Bousfield GR, Ben-Menahem D. The recombinant equine LHβ subunit combines divergent intracellular traits of human LHβ and CGβ subunits.. Theriogenology 2015 Jun;83(9):1469-76.
- Antczak DF, de Mestre AM, Wilsher S, Allen WR. The equine endometrial cup reaction: a fetomaternal signal of significance.. Annu Rev Anim Biosci 2013 Jan;1:419-42.
- Clay CM, Nelson SE, Digregorio GB, Campion CE, Wiedemann AL, Nett RJ. Cell-specific expression of the mouse gonadotropin-releasing hormone (GnRH) receptor gene is conferred by elements residing within 500 bp of proximal 5' flanking region.. Endocrine 1995 Aug;3(8):615-22.
- Tremblay JJ, Drouin J. Egr-1 is a downstream effector of GnRH and synergizes by direct interaction with Ptx1 and SF-1 to enhance luteinizing hormone beta gene transcription.. Mol Cell Biol 1999 Apr;19(4):2567-76.
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