Les récepteurs des gonadotrophines.

Abstract

Le recepteur de l' hormone luteinisante (LH) est le premier d' une nouvelle famille de recepteurs a sept segments transmembranaires couples aux proteines G dont l' ADNc a ete clone. Les recepteurs de l' hormone folliculostimulante (FSH) et de l' hormone thyreostimulante (TSH) appartiennent a la meme sous-famille. Leur caracteristique est l' existence d' un volumineux domaine extracellulaire, apparente aux glycoproteines riches en leucine, responsable de la liaison a l' hormone. Les genes des recepteurs de la LH et de la FSH sont de tres grande taille (> 70kpb) et sont tous deux localises au niveau du chromosome 2p21, ce qui evoque un mecanisme de duplication genique. Ils comprennent respectivement 11 et 10 exons. Tous les introns sont localises au niveau de la partie codant pour le domaine extracellulaire du recepteur. Des formes solubles du recepteur de la LH, engendrees par epissage alternatif, sont physiologiquement exprimees. Les etudes de mutagenese dirigee ont permis de donner des informations sur les relations structure-fonction de ces recepteurs. Les recepteurs des gonadotrophines ont egalement servi de modele dans l' etude du trafic, et notamment de l' adressage polarise de ce groupe de recepteurs.

The LH/CG receptor was the first member of a novel family of G protein coupled receptors to be cloned. This family also includes FSH and TSH receptors. These receptors exhibit a seven transmembrane domain characteristic of all G protein coupled receptors, but a large extracellular domain involved in ligand binding and related to leucine-rich glycoproteins is specific of this family of receptors. Different forms of LH and FSH receptors are physiologically expressed: a mature transmembrane species corresponding to the functional receptor and a high mannose precursor which accumulates inside the cell. Variant forms of the LH receptor generated by alternative splicing and lacking transmembrane domain have been isolated. They can potentiate the full length receptor function. Human LH and FSH receptor genes are both localised on chromosome 2p21. The genes are very large (> 70 kpb). Introns are restricted to the 5' part encoding the extracellular domain of the receptor. The intracellular traffic of the LH receptor has been studied by immunoelectron microscopy in Leydig cells and in transfected L cells. The same approach was used to study the receptor-mediated transendothelial transfer of hCG in testicular microvasculature. The physiological polarisation of the FSH receptor has been reproduced in MDCK cells and a basolateral targeting signal identified. Mutagenesis studies gave informations on structure-function relationships. Mice with deleted FSHbeta and FSH receptor genes have been obtained. Altogether these models help understanding the role of gonadotropins and their receptors in the ontogenesis and differentiation of gonads. [References: 40]