Earticle

초록

영어

Equine follicle-stimulating hormone (eFSH) is a member of the glycoprotein family with luteinizing hormone (LH), thyroid stimulating hormone (TSH), and equine chorionic gonaodotropin (eCG). These receptors called G protein-coupled (GPCR) receptor were synthesized in granulosa/theca and Sertoli/Leydig cells in ovary/testis. GPCRs are key signaling proteins that regulate nearly every aspect of cell function. GPCRs relay information from extracellular stimuli to intracellular responses in a wide range of physiological and pathological processes. All of the receptors in this superfamily transverse the plasma membrane with seven highly conserved a-helices oriented with an extracellular amino terminus and an intracellular carboxy terminus. To access the functional effect of the activation mutant (D566G) and inactivations (A189V, N191I, R572C, A574V, and R633H) in the eFHSR, wild type and the mutated eFSHR were transiently expressed in CHO-K1 cells and cAMP accumulation was measured. The activity of activation mutant at residue 556 exhibits a 9.4-fold increase in basal cAMP accumulation. In the inactivation mutants, EC50 values of the 189 site was 73.2% compared to that of wild type receptor. The other site (191) does not affect in the cAMP responsiveness. Other 3 sites (572, 574, and 633), the EC50 values were detected 109.7, 118.9, and 115.3%, respectively. The mutation is localized in a crucial region of the transmembrane domain, highly conserved in all glycoprotein hormone receptors, and within the FSH receptor of different species. The same site (Asp-Gly) has been previously reported to lead to constitutive activation of these receptors (LHR, and TSHR). Those receptors were found in patients with pseudoprecocious puberty and thyroid adenoma, respectively. In summary, we have identified constitutively activating point mutations and inactivating mutations of eFSHR in CHO-K1 cells. Knowledge of those mutations will facilitate genetic counseling and diagnosis, as well as provide the basis to study the three-dimensional conformation of the receptor domains involved in ligand-binding and G protein activation. To our knowledge, this remains the sole example of a naturally occurring activating mutation of the FSH receptor described so far. Thus, the significance of naturally occurring polymorphisms in the FSH receptor is still unknown. We insist that some receptor variant or combination of variants is related to a higher incidence of reproductive disorders.

키워드

저자

• Munkhzaya Byambaragchaa [ Department of Animal Biotechnology, Graduate School of Future Convergence Technology, Hankyong National University, Anseong 17579, Korea ]
• Tae-Young Ahn [ Department of Animal Biotechnology, Graduate School of Future Convergence Technology, Hankyong National University, Anseong 17579, Korea ]
• Kwan-Sik Min [ Department of Animal Biotechnology, Graduate School of Future Convergence Technology, Hankyong National University, Anseong 17579, Korea ]

참고문헌

발행기관

간행물

표지보기 관심저널 등록

• 간행물명

  발생공학 국제심포지엄 및 학술대회 [International Symposium on Developmental Biotechnology]

• 간기

  연간

• 수록기간

  2004~2018

• 십진분류

  KDC 527 DDC 636