Increased glycoprotein hormone yield in stably transfected CHO cells using human serum albumin signal peptide for...

Heterologous signal peptides enable increasing titers of recombinant proteins in mammalian cell culture. Four human heterodimeric glycoprotein hormones (follicle-stimulating hormone, FSH; luteinizing hormone, LH; chorionic gonadotropin, CG; and thyroid-stimulating hormone, TSH) were expressed in stably transfected CHO cells when varying signal peptides of their β-subunits. The signal peptide of human serum albumin proved to be the most effective for the glycoprotein hormone family. The cell specific productivity was increased for LH (2.5 pg/cell, 4-fold increase), TSH (1.6 pg/cell, 13-fold increase), and CG (1.0 pg/cell, 60%-increase). According to the Western blotting and quantitative PCR data, the productivity increase is associated with an increase in the efficiency of translation and translocation of β-subunits of hormones in the endoplasmic reticulum due to their coupling with the heterologous signal peptides.