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E Milgrom

The present status of endocrinology in France is characterized by features that are in a minor part specific for this discipline but in a major part shared with other fields of science and medicine. This is also true for international comparisons, especially in research. French endocrinologists are submitted to the same international competition and must publish in the same journals as their foreign counterparts. However, they have also very specific training, funding and promotion systems.


Research is performed mainly by laboratories funded by INSERM (agency for medical research), CNRS (agency for general research) and the Universities. In comparison with other countries, relatively little research, especially fundamental research, is carried out in pharmaceutical companies. University funding is very low, so the best laboratories tend to belong to CNRS or INSERM. The creation of an INSERM (or a CNRS) Unit is very competitive. A Unit is reassessed every 4 years, but

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M Misrahi and E Milgrom

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E. Milgrom, M. Luu Thi and E. E. Baulieu


The hormonal control of the amount of steroid receptors in the target cells may be a clue for the understanding of hormone receptivity and of integrated hormonal mechanisms (for example cyclic sequences of events). As a model system, the guinea pig uterus progesterone receptor has been studied. After an analysis of the theoretical and practical parameters which should be taken into account in order to measure specifically the receptor binding sites, the protein-RNA synthesis mediated induction of the progesterone receptor by oestradiol is described. The half life of the receptor is about 5 days in hormone deprived animals (in vivo experiments), but in case of progesterone administration it decays very rapidly, due probably to a rise in inactivation rate. Sequential administration of oestradiol and progesterone reproduces the changes observed during the oestrous cycle. The mechanism of the apparent inactivation of the receptor after binding of its own hormonal ligand is unknown.

Some information available about the hormonal control of the androgen and oestrogen receptors in their respective target organs is reviewed.

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E. E. Baulieu, J. P. Raynaud and E. Milgrom


A brief review of the characteristics of steroid binding proteins found in the plasma and in some target organs is presented, followed by some general remarks on binding »specificity« and binding parameters. Useful techniques for measuring binding parameters at equilibrium are reported, both those which keep the equilibrium intact and those which implicate its disruption. A concept is developed according to which the determination of a specific steroid binding protein is based on the »differential dissociation« of the several steroid binding complexes present in most biological mixtures.

Methods which allow determination of the kinetic parameters of the binding systems are also presented.

Various representations of the binding and therefore different modes of graphic representation and calculation are discussed, including the recent »proportion graph« method.

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P Chanson, N De Roux, J Young, JM Bidart, P Jacquet, M Misrahi, E Milgrom and G Schaison

The monoclonal origin of gonadotropin-secreting pituitary adenomas has been well demonstrated but only few molecular abnormalities have so far been recognized in these tumors. For many years, several authors have suggested a role for GnRH and/or GnRH receptors (GnRH-R) in the development of these pituitary adenomas. To test the hypothesis that mutant genes encoding a constitutively activated GnRH-R might be involved in the pathogenesis of these tumors, the sequence of the GnRH-R gene was analyzed in tumoral pituitary tissue obtained from ten patients (six female, four male). The pituitary gonadotropin-secreting adenoma was associated with in vivo hypersecretion of FSH, LH and/or free alpha-subunit (n = 7) or was clinically silent (normal plasma levels of gonadotropins or free alpha-subunit, n = 3). In all cases, immunocytochemical studies of the removed adenoma confirmed their gonadotroph nature by revealing positivity for FSH, LH and/or alpha-subunit. Genomic DNA was extracted from the pathological tissue obtained at neurosurgery. Eight sequencing primers were used to amplify the three exons of the GnRH-R gene from tumoral DNA. The entire coding sequence of the GnRH-R gene was sequenced in the ten adenomas. No mutation was found in any of the tumor specimens examined. In conclusion, mutations in the GnRH receptor coding sequence occur infrequently if at all in gonadotropin-secreting pituitary adenomas.