Both of the beta-subunit carbohydrate residues of follicle-stimulating hormone determine the metabolic clearance rate and in vivo potency.
FSH is a glycoprotein hormone required for the development and maturation of the ovarian follicle and for spermatogenesis. FSH is glycosylated at asparagine residues 52 and 78 on the alpha-subunit and residues 7 and 24 on the beta-subunit. In vitro, the carbohydrate residue at position alpha 52 is required for signal transduction. To define the contribution of the carbohydrate residues to FSH potency in vivo, we assessed the MCR and in vivo bioactivity of site-specifically deglycosylated recombinant human FSH variants. The removal of the beta-subunit carbohydrate residues significantly (P < 0.05) affected the MCR and resulted in significantly (P < 0.05) reduced in vivo bioactivity. For all recombinant human FSH variants, a strong correlation (r = 0.90; P < 0.01) was observed between MCR and in vivo potency, indicating that the circulatory half-life of the hormone appears to be the primary determinant of in vivo bioactivity. Although the beta-subunit carbohydrate residues have the greatest effect in determining FSH potency in vivo; the alpha 52 residue, important in vitro, has no effect on either MCR or in vivo potency. This study highlights the difficulties of translating in vitro results to whole animal physiology.
Bishop
L A
LA
Garvan Institute of Medical Research, St. Vincent's Hospital, Darlinghurst, Sydney, Australia.
Nguyen
T V
TV
Schofield
P R
PR
D000818:Animals; D002241:Carbohydrates / Q000737:chemistry; D005260:Female; D005640:Follicle Stimulating Hormone / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D014644:Genetic Variation; D006207:Half-Life; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010053:Ovary / Q000033:anatomy & histology / Q000187:drug effects; D011487:Protein Conformation; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
D002241:Carbohydrates; D011994:Recombinant Proteins; D005640:Follicle Stimulating Hormone