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Journal of Endocrinology (2008) 196, 593-600       DOI: 10.1677/JOE-07-0473
© 2008 Society for Endocrinology
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Single-chain human gonadotropin analogs induce follicle development in sheep

Elyse P Lemke, Betty M Adams, Albina Jablonka-Shariff1, Irving Boime1 and Thomas E Adams

Department of Animal Science, University of California, Davis, California 95616, USA1 Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St Louis, Missouri 63110, USA

(Correspondence should be addressed to T E Adams; Email: teadams{at}ucdavis.edu)

The biopotency of single-chain analogs of human hFSH, human chorionic gonadotropin (hCG), and a dually active gonadotropin construct (FcCGβ{alpha}) was examined. Sheep (bwt=61.4±1.1 kg; n=6 ewes/treatment) received a single injection (5 IU/kg, i.v.) of the hFSH analog (Fc{alpha}), the hCG analog (CGβ{alpha}), FcCGβ{alpha}, or Fc{alpha} and CGβ{alpha}. Control animals received conditioned media. Ovulation was induced 3 days after analog administration using hCG (1000 IU, i.v.). Basal serum concentrations of estradiol (E2) were maintained in control animals. Neither Fc{alpha} nor CGβ{alpha} alone induced significant E2 production during the pre-hCG period. Conversely, serum concentrations of E2 were increased (P<0.05) 2 days after administration of FcCGβ{alpha} or Fc{alpha}+ CGβ{alpha}. Although P4 concentrations were maintained at basal levels in control animals, significant increase was noted in all other treatment groups during the post-hCG period. Final ovarian weight was significantly increased (P<0.05) in animals receiving Fc{alpha}, Fc{alpha}+ CGβ{alpha}, or FcCGβ{alpha}, but not CGβ{alpha} alone. Most of the ovarian enlargement was attributed to the formation of corpora lutea. Collectively, these observations demonstrate that the single-chain analogs of the human gonadotropins are active in sheep. The construct with singular FSH activity supports follicle development but not E2 production. Conversely, the construct that incorporates β-domains from both CG and FSH has dual activity. The long-lived nature of the single-chain constructs suggests that these recombinant gonadotropins may be effective alternatives to pituitary- or placenta-derived gonadotropins in out-of-season breeding and/or superovulation protocols.







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