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- Title
Development and characterization of a long-acting recombinant hFSH agonist.
- Authors
Klein, J.; Lobel, L.; Pollak, S.; Lustbader, B.; Ogden, R.T.; Sauer, M.V.; Lustbader, J.W.
- Abstract
BACKGROUND: Fusion of the carboxyterminal peptide (CTP) of hCG to FSH results in a follitropin agonist with an extended half‐life, presumably due to the four O‐oligosaccharides on the CTP. Alternatively, an rhFSH analogue containing additional N‐linked carbohydrate is described in this report. METHODS: A DNA sequence containing two N‐oligosaccharide signal sequences was ligated into a vector containing hFSHβ‐ and α‐subunit encoding cDNA, and expressed in CHO‐K1 cells. In‐vitro bioactivity of the single‐chain hormone was assessed in CHO cells expressing the hFSH receptor. Pharmacokinetic values were derived from serial serum assays of the analogue in immature female rats following a single i.v. injection. In‐vivo bioactivity was assessed by measuring ovarian weight gain 3 days post‐injection. RESULTS: rhFSH‐N2 and native rhFSH induced comparable levels of cAMP in vitro. t1/2 for native rhFSH, rhFSH‐CTP and rhFSH‐N2 were 3.7, 7.1 and 7.3 h respectively. Rats receiving rhFSH‐N2 had a mean ± SD ovarian weight 3 days post‐i.v. injection (22 ± 3.6 mg) significantly greater than rats receiving rhFSH and saline (16.7 ± 1.5 and 15.3 ± 0.47 mg respectively, P < 0.05). CONCLUSIONS: rhFSH‐N2 has prolonged half‐life and increased bioactivity compared with native rhFSH. This rhFSH agonist, and other analogues containing additional N‐oligosaccharides may have important clinical applications.
- Publication
Human Reproduction, 2003, Vol 18, Issue 1, p50
- ISSN
0268-1161
- Publication type
journal article
- DOI
10.1093/humrep/deg024