Biotechnological tools to study gonadotropin actions in European sea bass (Dicentrarchus labrax)

Abstract

The gonadotropins, follicle stimulating hormone (Fsh) and the luteinizing hormone (Lh), are central endocrine regulators of reproduction in vertebrates. They are heterodimeric glycoproteins secreted by the pituitary gland that act by binding specific receptors located in the gonads, controlling different steps of gametogenesis and steroidogenesis. The structural duality of these hormones is well defined, but so far their individual roles are not clear in many fish species due to the lack of tools for their study. In European sea bass (Dicentrarchus labrax) the isolation of the genes coding for the gonadotropin subunits and receptors allowed firstly to study their expression profiles. Later, to overcome the limitation of native hormones, recombinant dimeric gonadotropins have been generated and used for functional studies in vitro and in vivo. In addition, the production of recombinant gonadotropin beta-subunits provided adequate antigens to raise antibodies, which were the basis for the development of detection methods for native gonadotropins. In this way, sea bass is one of the few teleost species where the amount of circulating and hypophysiary gonadotropins can be quantified. All the sea bass recombinant gonadotropins produced are functionally active, showing no cross-reaction between receptors. However, the production rates and in vivo stability of these recombinant forms showed remarkable differences depending on the cell expression system and DNA construct used, leading in some cases to the rapid clearance from circulation of the exogenously administered hormone. For this reason, gene-based therapies using somatic transfer of gonadotropin genes have also been tested as an alternative for hormone delivery in vivo, resulting in different studies on gonadotropin actions in spermatogenesis.