Progress Medal 2004 is awarded to
MD , Ph.D
Presently Chief Investigator (Directeur de Recherches, classe exceptionnelle) at I'Institut National de la Santeet de la Recherche Medicale (INSERM) affiliated with Paris-Sud University Paris, France.
Foetal sexual differentiation, and particularly the role of anti-Müllerian hormone (AMH), have concentrated the professional enthusiasm of Dr Nathalie Josso. The existence of this foetal testicular factor, different from testosterone and responsible for the regression of Müllerian ducts -the primordia of the uterus and Fallopian tubes- in early male development had been postulated by Alfred Jost in the 1950's. However, the nature of the "Müllerian inhibitor" remained unknown. A paediatrician, intrigued by the intersex conditions, Nathalie Josso joined Dr Jost's laboratory and obtained a Ph.D. degree under his supervision in 1971. These were the first steps that led towards a comprehensive understanding of the foetal testicular factor that Dr. Josso named AMH.
A Parisian passionate for her natal city, Nathalie Josso developed her professional career as an Investigator at the INSERM and a consultant in Paediatric Endocrinology in top level Parisian institutions. Nathalie first led a research team at the INSERM Unit directed by Dr Frézal at the Hôpital des Enfants Malades for more than 20 years. Between 1971 and 1973, Nathalie's team was the first to purify AMH from bovine foetal testes and show that AMH was produced exclusively by Sertoli cells, achievements rapidly recognised overseas and honoured with invitations to deliver the Lawson Wilkins Memorial Lecture in Baltimore (USA, 1975) and the Laurentian Hormone Conference in Mont Tremblant (Canada, 1976). Exigent for excellence, Nathalie drove her team to the development of precious research tools, e.g. anti-AMH monoclonal antibodies, which finally enabled the identification of AMH as a disulfide-bonded glycoprotein dimer. Nathalie has always pointed out the importance of applying novel technologies to enhance the advancement of a research project. She kept at the state-of-the-art and encouraged her co-workers to develop and apply the most adequate techniques in the search for transcendental knowledge. Using novel genetic and molecular techniques, Nathalie's team cloned the bovine AMH cDNA in 1986 (almost at the same time as the human gene was cloned in Boston by Dr Richard Cate) and mapped the human AMH gene to chromosome 19 in 1987.
In 1986, Nathalie Josso founded the Unité de Recherches sur l'Endocrinologie du Développement (INSERM), which she directed for 12 years. The research unit was hosted by one of the most outstanding French academic institutions, the Ecole Normale Supérieure. Further achievements were the molecular characterisation of the Persistent Müllerian Duct Syndrome (PMDS), the demonstration that Sertoli cell AMH production is regulated at puberty by an intricate interaction between testosterone, FSH and meiotic germ cells, and the development of AMH assays enabling the use of its determination in serum as a diagnostic tool.
Finally, Nathalie's group, in collaboration with Dr Cate (Boston, USA), was the first to clone the AMH receptor type II, a specific transmembrane protein with serine/threonine kinase activity and to demonstrate mutations in its gene result in AMH insensitivity, characteristic of one sub-type of PMDS. Furthermore, Nathalie's lab showed that AMH receptors are present on Leydig cells, where AMH exerts a repressive effect on cell differentiation and steroidogenic capacity. In collaboration with Dr Massagué (New York), Nathalie's group identified a type I AMH receptor and was the first to show that AMH signals through Smad proteins.
Dr Nathalie Josso has devoted her intellect and efforts with passion to a clearly and brilliantly delineated research subject. Her work has led world-wide research on AMH for almost 40 years and has settled the basis for the relentless search of further knowledge on the subject.
A tribute by Rodolfo Rey MD, PhD