Go to Top Go to Bottom
Anim Biosci > Accepted Articles
https://doi.org/10.5713/ab.21.0246    [Accepted] Published online August 24, 2021.
Functional characterization of naturally-occurring constitutively activating/inactivating mutations in equine follicle-stimulating hormone receptor (eFSHR)
Munkhzaya Byambaragchaa1  , Tae-Young Ahn1  , Seung-Hee Choi1  , Myung-Hwa Kang2  , Kwan-Sik Min1,3,* 
1Animal Biotechnology, Graduate School of Future Convergence Technology, Hankyong National University, Ansung 17579, Korea
2Department of Food Science and Nutrition, Hoseo University, Asan 31499, Korea
3School of Animal Life Convergence Science, Institute of Genetic Engineering, Hankyong National University, Ansung 17579, Korea
Correspondence:  Kwan-Sik Min,Email: ksmin@hknu.ac.kr
Received: 27 May 2021   • Revised: 29 June 2021   • Accepted: 12 July 2021
Abstract
Objective
Follicle-stimulating hormone (FSH) is the central hormone involved in mammalian reproduction, maturation at puberty, and gamete production that mediates its function by control of follicle growth and function. The present study investigated the mutations involved in the regulation of FSH receptor (FSHR) activation.
Methods
We analyzed seven naturally-occurring mutations that were previously reported in human FSHR (hFSHR), in the context of equine FSHR (eFSHR); these include one constitutively activation variant, one allelic variant, and five inactivating variants. These mutations were introduced into wild-type eFSHR (eFSHR-wt) sequence to generate mutants that were designated as eFSHR-D566G, -A306T, -A189V, -N191I, -R572C, -A574V, and -R633H. Mutants were transfected into PathHunter EA-parental CHO-K1 cells expressing β-arrestin. The biological function of mutants was analyzed by quantitating cAMP accumulation in cells incubated with increasing concentrations of FSH,
Results
Cells expressing eFSHR-D566G exhibited an 8.6-fold increase in basal cAMP response, as compared to that in eFSHR-wt. The allelic variation mutant eFSHR-A306T was not found to affect the basal cAMP response or EC50 levels. On the other hand, eFSHR-D566G and eFSHR-A306T displayed a 1.5- and 1.4-fold increase in the maximal response, respectively. Signal transduction was found to be completely impaired in case of the inactivating mutants eFSHR-A189V, -R572C, and -A574V. When compared with eFSHR-wt, eFSHR-N191I displayed a 5.4-fold decrease in the EC50 levels (3910 ng/mL) and a 2.3-fold decrease in the maximal response. In contrast, cells expressing eFSHR-R633H displayed in a similar manner to that of the cells expressing the eFSHR-wt on signal transduction and maximal response.

Conclusion

The activating mutant eFSHR-D566G greatly enhanced the signal transduction in response to FSH, in the absence of agonist treatment. We suggest that the state of activation of the eFSHR can modulate its basal cAMP accumulation.
Keywords: Allelic Variant Mutation, Constitutive Activation, Equine Follicle-Stimulating Hormone Receptor, Inactivating mutation, cAMP Responses
TOOLS
METRICS Graph View
  • 0 Crossref
  •  0 Scopus
  • 123 View
  • 10 Download
Related articles


Editorial Office
Asian-Australasian Association of Animal Production Societies(AAAP)
Room 708 Sammo Sporex, 23, Sillim-ro 59-gil, Gwanak-gu, Seoul 08776, Korea   
TEL : +82-2-888-6558    FAX : +82-2-888-6559   
E-mail : animbiosci@gmail.com               

Copyright © 2021 by Animal Bioscience.

Developed in M2PI

Close layer
prev next