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Biomolecules2025; 15(2); 289; doi: 10.3390/biom15020289

Enhanced Production and Functional Characterization of Recombinant Equine Chorionic Gonadotropin (rec-eCG) in CHO-DG44 Cells.

Abstract: Equine chorionic gonadotropin (eCG) hormone, comprising highly glycosylated α- and β-subunits, elicits responses similar to follicle-stimulating hormone (FSH) and luteinizing hormone (LH) in non-equid species. This study aimed to establish a mass production of recombinant eCG (rec-eCG) using CHO DG44 cells. Single-chain rec-eCG β/α was expressed in CHO DG44 cells. FSH- and LH-like activities were evaluated in CHO-K1 and HEK 293 cells expressing the equine LH/CG receptor (eLH/CGR), rat LH/CGR (rLH/CGR), and rFSHR. pERK1/2 activation and β-arrestin 2 recruitment were assessed in PathHunter CHO-K1 cells. The expression from one, among nine isolates, peaked at 364-470 IU/mL on days 9 and 11. The molecular weight of rec-eCG β/α ranged from 40 to 47 kDa, with two distinct bands. PNGase F treatment reduced the molecular weight by 8-10 kDa, indicating N-glycosylation. Rec-eCG β/α demonstrated dose-responsive cAMP activity in cells expressing eLH/CGR, with enhanced potency in rLH/CGR and rFSHR. Phospho-ERK1/2 activation peaked at 5 min before declining rapidly. β-arrestin 2 recruitment was receptor-mediated in cells expressing hFSHR and hLH/CGR. This study provides insights into the mechanisms underlying eCG's FSH- and LH-like activities. Stable CHO DG44 cells can produce large quantities of rec-eCG. eCG activates pERK1/2 signaling via the PKA/cAMP pathway and facilitates β-arrestin 2 recruitment.
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Publication Date: 2025-02-14 PubMed ID: 40001592PubMed Central: PMC11853024DOI: 10.3390/biom15020289Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This research focuses on the mass production and functionality of a recombinant form of the hormone equine chorionic gonadotropin (rec-eCG) using a specific cell line. The study revealed methods to produce large amounts of rec-eCG and offered insights into how the hormone triggers particular cellular responses.

Study Objective and Overview

  • This research aimed to create a large-scale production system of a recombinant version of the hormone equine chorionic gonadotropin (rec-eCG) using a cell line referred to as CHO DG44. The team also sought to examine the functional characteristics of the hormone.
  • Equine chorionic gonadotropin (eCG) is made of highly glycosylated α- and β-subunits, and it elicits responses similar to follicle-stimulating hormone (FSH) and luteinizing hormone (LH) in non-equid species. Understanding how this hormone operates can provide meaningful insights into reproductive biology and hormone-related medical applications.

Manufacture of the Recombinant Hormone

  • The scientists used a specific pair of cells, known as CHO DG44 cells, to generate a single-chain form of rec-eCG β/α. A total of nine isolates (cell cultures originating from a single cell) were tested, but only one showed significant productivity, with the expression peaking between 364-470 IU/mL on days 9 and 11.
  • The recombinant hormone contained two distinct bands and had a molecular weight that varied between 40-47 kDa. Following treatment with PNGase F, the molecular weight dropped by 8-10 kDa, indicating the presence of N-glycosylation, a process in which sugars are attached to proteins.

Functional Characterization of rec-eCG

  • en>CHO-K1 and HEK 293 cells were used to evaluate FSH- and LH-like activities. The hormone showed a dose-responsive cAMP activity in cells expressing eLH/CGR, with a higher potency observed in rLH/CGR and rFSHR. This indicates that the hormone can interact with and signal through specific receptors.
  • The activation of a signalling molecule, phospho-ERK1/2, peaked at 5 minutes before declining quickly. This result suggests that the hormone can trigger rapid intracellular signalling pathways related to cell division and other processes.
  • Furthermore, the research team evaluated β-arrestin 2 recruitment, a process related to the regulation of signal transmission in cells. The β-arrestin 2 recruitment was receptor-mediated in cells expressing hFSHR and hLH/CGR, indicating that the hormone facilitates this recruitment.

Implication and Conclusion

  • The study provides valuable insights into eCG’s FSH- and LH-like activities, along with a method for mass-production of rec-eCG using stable CHO DG44 cells.
  • This investigation also identified how eCG activates the signaling pathway of pERK1/2 via the PKA/cAMP pathway. The results of this study imply the potential use of eCG for reproductive biology research and medical applications that require understanding of hormone behaviour.

Cite This Article

APA
Byambaragchaa M, Park SH, Park MH, Kang MH, Min KS. (2025). Enhanced Production and Functional Characterization of Recombinant Equine Chorionic Gonadotropin (rec-eCG) in CHO-DG44 Cells. Biomolecules, 15(2), 289. https://doi.org/10.3390/biom15020289

Publication

Biomolecules
ISSN: 2218-273X
NlmUniqueID: 101596414
Country: Switzerland
Language: English
Volume: 15
Issue: 2
PII: 289

Researcher Affiliations

Byambaragchaa, Munkhzaya
  • Carbon-Neutral Resources Research Center, Hankyong National University, Anseong 17579, Republic of Korea.
  • Institute of Genetic Engineering, Hankyong National University, Anseong 17579, Republic of Korea.
Park, Sei Hyen
  • Graduate School of Animal Biosciences, Hankyong National University, Anseong 17579, Republic of Korea.
Park, Myung-Hum
  • TNT Research, Sejong 30141, Republic of Korea.
Kang, Myung-Hwa
  • Department of Food Science and Nutrition, Hoseo University, Asan 31499, Republic of Korea.
Min, Kwan-Sik
  • Carbon-Neutral Resources Research Center, Hankyong National University, Anseong 17579, Republic of Korea.
  • Institute of Genetic Engineering, Hankyong National University, Anseong 17579, Republic of Korea.
  • Graduate School of Animal Biosciences, Hankyong National University, Anseong 17579, Republic of Korea.
  • Division of Animal Bioscience, School of Animal Life Convergence Sciences, Hankyong National University, Anseong 17579, Republic of Korea.

MeSH Terms

  • Animals
  • CHO Cells
  • Cricetulus
  • Humans
  • Recombinant Proteins / metabolism
  • Recombinant Proteins / genetics
  • HEK293 Cells
  • Horses
  • Rats
  • Chorionic Gonadotropin / pharmacology
  • Chorionic Gonadotropin / metabolism
  • Receptors, LH / metabolism
  • Receptors, LH / genetics
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • beta-Arrestin 2 / metabolism
  • beta-Arrestin 2 / genetics
  • Mitogen-Activated Protein Kinase 3 / metabolism
  • Gonadotropins, Equine / pharmacology
  • Luteinizing Hormone / metabolism
  • Luteinizing Hormone / pharmacology
  • Follicle Stimulating Hormone / metabolism
  • Follicle Stimulating Hormone / pharmacology
  • Cyclic AMP / metabolism
  • Glycosylation

Grant Funding

  • RS202400335122 / Korean Research Foundation Program

Conflict of Interest Statement

The authors declare no conflicts of interest.

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