Gonadotropin actions in European sea bass: endocrine roles and biotechnological applications

Abstract

The follicle stimulating hormone (Fsh) and the luteinizing hormone (Lh) are central endocrine regulators of gonad function in vertebrates. These gonadotropins act by binding and activating their specific receptors that are located in certain cell types of the gonads. In fish, the differential roles of these hormones are being progressively elucidated with the development of different tools for their study. In the case of European sea bass Dicentrarchus labrax, the isolation of the genes coding for the gonadotropin subunits and receptors allowed in first instance for expression studies. Later, to overcome the limitation of native hormones, recombinant dimeric gonadotropins have been generated, which show different functional characteristics depending on the cell system and DNA construct. In addition, single gonadotropin beta-subunits have been produced and used as antigens for antibody production. This last approach has allowed the development of detection methods for native gonadotropins being the European sea bass one of the few species where both gonadotropins can be detected in their native form. The generation of antibodies has also allowed for their cellular localization and co-localization with other factors, helping to a better understanding of their function. By administration of the recombinant gonadotropins to gonad tissues cultured in vitro we have studied their effects on steroidogenesis, the activated intracellular pathways and their target genes. Their administration in vivo has also been tested both for basic studies and as a biotechnological approach. In this frame, it is known from different studies in mammals that exogenous administration of native hormones in cases of deficiency, including assisted reproduction, can be unsatisfactory due to their rapid clearance from circulation or limited availability. Other than the production of recombinant hormones gene-based therapies by using somatic gene transfer are offered as an alternative. Such an approach has been tested in sea bass for gonadotropin delivery in vivo. The hormones produced by the injected genes were functional and have allowed for different studies on gonadotropin action in spermatogenesis. All together, the use of gene therapy for hormone replacement in fish is a real alternative to the production of recombinant gonadotropins for in vivo use, due to the low cost of production and the high persistence of the injected DNA, and has a broad range of potential applications such as its use in out-of-season breeding programs or reproductive dysfunctions in fish species.