Evidence that the alpha-subunit influences the specificity of receptor binding of the equine gonadotrophins.
Abstract: Horse LH/chorionic gonadotrophin (eLH/CG) exhibits, in addition to its normal LH activity, a high FSH activity in all other species tested. Donkey LH/CG (dkLH/CG) also exhibits FSH activity in other species, but about ten times less than the horse hormone. In order to understand the molecular basis of these dual gonadotrophic activities of eLH/CG and dkLH/CG better, we expressed, in COS-7 cells, hybrids between horse and donkey subunits, between horse or donkey alpha-subunit and human CG beta (hCG beta), and also between the porcine alpha-subunit and horse or donkey LH/CG beta. The resultant recombinant hybrid hormones were measured using specific FSH and LH in vitro bioassays which give an accurate measure of receptor binding specificity and activation. Results showed that it is the beta-subunit that determines the level of FSH activity, in agreement with the belief that it is the beta-subunit which determines the specificity of action of the gonadotrophins. However, donkey LH/CG beta combined with a porcine alpha-subunit exhibited no FSH activity although it showed full LH activity. Moreover, the hybrid between horse or donkey alpha-subunit and hCG beta also exhibited only LH activity. Thus, the low FSH activity of dkLH/CG requires an equine (donkey or horse) alpha-subunit combined with dkLH/CG beta. These results provide the first evidence that an alpha-subunit can influence the specificity of action of a gonadotrophic hormone.
Publication Date: 1998-01-01 PubMed ID: 9415058DOI: 10.1677/joe.0.1550241Google 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.
- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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This research investigated the role of the alpha-subunit in defining the specificity of gonadotrophic hormone activity, primarily focusing on the hormones in horses and donkeys. The results suggested that while the beta-subunit usually determines activity specificity, the alpha-subunit can also influence it under certain conditions.
Research Aim and Methodology
- The research aimed to understand the molecular basis for the dual gonadotrophic activities of eLH/CG and dkLH/CG hormones in horses and donkeys, which have shown LH (luteinizing hormone) and FSH (follicle-stimulating hormone) activity in various species.
- To achieve the goal, the researchers expressed hybrids of horse and donkey subunits and other specific combinations in COS-7 cells. They created hybrid hormones involving horse or donkey alpha-subunits with human CG beta (hCG beta) and also the porcine alpha-subunit with horse or donkey LH/CG beta-subunits.
- These resultant recombinant hybrid hormones were measured using specific FSH and LH in vitro bioassays, providing accurate measures of receptor binding specificity and activation.
Research Findings
- The results showed that the beta-subunit typically determines the level of FSH activity, aligning with the existing belief that the beta-subunit determines the specificity of action of the gonadotrophins.
- However, some unique findings came when they examined some specific hybrids. The hybrid hormone consisting of a donkey LH/CG beta combined with a porcine alpha-subunit showed only LH activity, with no FSH activity.
- Similarly, the hybrid involving horse or donkey alpha-subunit and hCG beta also exhibited only LH activity.
- This suggests that the lower FSH activity of dkLH/CG requires a combination of an equine (donkey or horse) alpha-subunit with dkLH/CG beta.
Conclusions
- In conclusion, this study provides the first evidence that the alpha-subunit can also influence the specificity of action of a gonadotrophic hormone, despite the common belief that the beta-subunit plays the decisive role. This newly found role of the alpha-subunit adds complexity to our understanding of gonadotrophic hormone action.
Cite This Article
APA
Chopineau M, Martinat N, Marichatou H, Troispoux C, Auge-Gouillou C, Stewart F, Combarnous Y, Guillou F.
(1998).
Evidence that the alpha-subunit influences the specificity of receptor binding of the equine gonadotrophins.
J Endocrinol, 155(2), 241-245.
https://doi.org/10.1677/joe.0.1550241 Publication
Researcher Affiliations
- Station de Physiologie de la Reproduction, Institut National de la Recherche Agronomique, URA INRA/CNRS 1291, Nouzilly, France.
MeSH Terms
- Animals
- Biological Assay
- COS Cells
- Chorionic Gonadotropin, beta Subunit, Human / metabolism
- Equidae / metabolism
- Follicle Stimulating Hormone / metabolism
- Glycoprotein Hormones, alpha Subunit / physiology
- Gonadotropins, Equine / metabolism
- Horses
- Leydig Cells / metabolism
- Luteinizing Hormone / metabolism
- Male
- Protein Binding
- Rats
- Receptors, Gonadotropin / metabolism
- Recombinant Proteins / metabolism
- Sensitivity and Specificity
Citations
This article has been cited 1 times.- 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.
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