IMIM - Institut Hospital del Mar d'Investigacions Mèdiques

Bioanalysis and analytical services Jordi Segura

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Growth

Growth Hormone is one of the hormones more prone to be abused both among sportsmen and also by parents of children with idiopathic short stature. A better knowledge of its detection and structural parameters are highly useful to better prevent is abuse, especially taking into account the complexity of its structure due to multiple isoforms (direct, spliced, proteolytically derived) present in the human body. Regarding detection, the interest is in the development of a analytical tools for measuring the ratio between the two most abundant endogenous growth hormone isoforms (20 and 22 kDa). Illicit use of a single isoform pharmaceutical would alter this ratio, through a feed-back mechanism, and in turn this would be an indication of abuse.

As described above for the Imagene project, the potential misuse of GH gene therapy is also a possibility to be prevented in the future and a project with a similar protocol to Imagene is being developed (Dopagen). Another alternative future way of producing high concentrations of GH is the application of Growth Hormone Secretagogues (Ghrelin analogues). A project to study the detection of those GH sectreagogues is being developed.

Elaboration of a single screening protocol that should pick-up the presence of exogenous growth hormone secretagogues (a heterogeneous family of structurally unrelated molecules that all stimulate the GHSR1a). The project is based on the disruption of a preformed receptor-radiolabeled ligand complex following incubation with a sample and measurement of the decrease of immobilised radiolabel. In addition, Ghrelin itself is becoming an important biomarker for several pathologies and therefore attention will be paid to its applicability in this regards.

Glycans: As many relevant hormones are glycoproteins, establishing in full detail the structures of the glycans contained in the endogenously produced and recombinantly expressed glycoprotein hormones is relevant (for erythropoietin a separate project is ongoing under the chapter of “oxygen delivery”). As the glycosylation is a posttranslational modification they will potentially carry the signature of the producing cell and through this signature a differentiation is sought.

As glycans are ubiquitous they do not illicit major antigenic response. Moreover, they usually trigger the initial phase of cellular communication. Yet, they can be degraded by circulating glycosidases. In order to provide from the best of both glycomimetics are synthesised containing thiourea glycosidic linkages that are subsequently conjugated to caveoles-type molecules (such as cyclodextrins) to develop efficient drug-transporters. The acrosome reaction is one of the early steps in fertilisation. In the initial interaction between oocytes and spermatozoa glycoprotein glycans appear to play a crucial role.

The main objective of this study is to identify the structural glycan epitope, present in oocyte glycoproteins, responsible for the interaction, as well as the carbohydrate binding entity on spermatozoa. For this different species, including bovine, porcine, murine, and human are investigated.

Analytical Methodology: The administration of growth agents to animals and doping substances to men share the need of rapid and reliable analytical determinations. Therefore an important objective is to develop analytical tools to detect or to improve the detection of the use of those forbidden substances.

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