Biological activity and metabolic clearance of a recombinant human thyrotropin produced in Chinese hamster ovary cells

Endocrinology. 1991 Jan;128(1):341-8. doi: 10.1210/endo-128-1-341.


The presence and specific structures of the oligosaccharides on TSH have been shown to be important for its production and bioactivity. Since the carbohydrate structure of a protein reflects the glycosylation apparatus of the host cells in which the protein is expressed, we examined the biological activity and metabolic clearance of a preparation of purified recombinant human (rh) TSH derived from a stable transfectant of Chinese hamster ovary cells. Carbohydrate compositional analysis of this rTSH showed it to be more highly sialylated than a nonrecombinant, cadaver-derived pituitary hTSH. In addition, no N-acetyl galactosamine was detectable in rhTSH, which implies the absence of terminal sulfate moieties, both of which are present in pituitary-derived TSH. The immunologic activity and porcine TSH receptor-binding activity of the preparation of rhTSH were 3- to 4-fold lower than those of a standard pituitary hTSH. The rhTSH showed a maximum stimulatory activity similar to that of pituitary hTSH in two different in vitro bioassays. However, rhTSH elicited about 3-fold and 5-fold less cAMP than pituitary TSH after stimulation of adenylyl cyclase in bovine thyroid membranes and the rat FRTL-5 cell line, respectively. Removal of sialic acid did not alter the immunologic activity of rhTSH. However, the potencies of rhTSH in receptor-binding, adenylyl cyclase, and FRTL-5 assays were increased 2.4-, 2.6- and 26.7-fold, respectively after sialic acid removal. These data suggest that the in vitro biological activity of rhTSH is influenced by its highly sialylated oligosaccharide chains. The rhTSH had a 2-fold lower metabolic clearance rate than pituitary TSH, resulting in a greater than 10-fold higher serum concentration of rhTSH at 3 h as compared to pituitary hTSH. After sialic acid removal, the rhTSH was cleared faster (7.5-fold) than pituitary hTSH, showing that its longer plasma half-life was due to its higher sialylation. Biologically active rhTSH should be of clinical value in the diagnosis and treatment of patients with thyroid cancer and as a pure hTSH reference preparation.

MeSH terms

  • Adenylyl Cyclases / metabolism
  • Animals
  • Carbohydrates / analysis
  • Cell Line
  • Cricetinae
  • Cricetulus
  • Cyclic AMP / metabolism
  • Female
  • Half-Life
  • Humans
  • Kinetics
  • Metabolic Clearance Rate
  • Ovary
  • Pituitary Gland / physiology
  • Rats
  • Receptors, Thyrotropin / metabolism
  • Recombinant Proteins / metabolism
  • Recombinant Proteins / pharmacokinetics*
  • Recombinant Proteins / pharmacology
  • Thyroid Gland
  • Thyrotropin / metabolism
  • Thyrotropin / pharmacokinetics*
  • Thyrotropin / pharmacology
  • Transfection


  • Carbohydrates
  • Receptors, Thyrotropin
  • Recombinant Proteins
  • Thyrotropin
  • Cyclic AMP
  • Adenylyl Cyclases