Expression of a single beta alpha chain protein of equine LH/CG in milk oftransgenic rabbits and its biological activity

Equine chorionic gonadotropin (eCG) is a heavily glycosylated glycoprotein composed of non-covalently linked alpha- and beta -subunits. eCG possesses the particularity to bind to both LH and FSH receptors in species other tha n horses and to have a prolonged plasma half-life. All these properties mak e it of utmost interest for livestock fertilization program. Up to now, the only source of eCG is the serum of pregnant mare. Rabbit mammary gland is considered as a system able to produce recombinant glycoproteins in suffici ent quantity for pharmaceutical use. Here we described the production of a recombinant single beta alpha chain of eLH/CG in the milk of transgenic rab bit. The construction of a single-chain permits to by-pass the problem of a ssociation-dissociation of the subunits. This recombinant hormone is greatl y expressed (21.7 mg/l) and presents similar in vitro LH and FSH bioactivit ies. However, B alpha eLH/CG shows an extremely rapid clearance (approximat e to 10 min), which could explain the absence of in vivo biological activit y. So the rabbit mammary gland is not appropriate Tor the production of a r ecombinant active eLH/CG. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.