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Enjalbert,Alain

Biographical outline

Alain Enjalbert was born in Paris on 27th. October, 1951. He completed his secondary schooling at the Lycée Jacques Decour before attending the Faculty of Science in Paris, where he graduated with a General Diploma in Biological Studies at the University of Paris VII (in 1971), followed by a Masters’ Degree in Biochemistry (in 1973) and a DEA diploma in Biophysics at the Pierre and Marie Curie University of Paris VI (in 1974). From 1973 to 1975, he was awarded a research fellowship to work at INSERM’s Neurobiological ResearchUnit 109 headed by Jean-Charles Schwartz.

After obtaining a "Doctorat de 3ème cycle" in 1975 in Biophysics at the Pierre and Marie Curie University of Paris VI, he was awarded a research fellowship by the Délégation Générale de la Recherche Scientifique et Technique (DGRST) to work at the Collège de France with the Biochemical Neuropharmacology Group (Inserm Unit 114 headed by Jacques Glowinski) and the Laboratory for Cell Physiology (1975-1976).

He was subsequently appointed to a series of positions at the CNRS (the French National Research Centre) as a Research Fellow (in 1976), Research Scientist (in 1981), 2nd. Class Research Director (in 1986), and 1st. Class Research Director (in 1991).

He then joined INSERM’s Neurobiology Unit 109 (1976-1980) before obtaining his Doctorate in Natural Science at the Pierre and Marie Curie University of Paris VII (in 1981). From 1981 to 1985, he worked at INSERM’s Neuro-endocrinological Unit 159 before joining the Unit for Research on the Dynamics of neuro-endocrine systems (1986-1992) headed by Claude Kordon.

He was then appointed at the head of the CNRS Mixed Research Unit 9941 on Neuroendocrine Cell Interactions at the University of the Mediterranean (1993-2007).

From 1997 to 2010, he directed the Functional Molecular Biology Unit at the Conception Hospital’s Biochemical Department in Marseille as a "University Professor Hospital Practician (in 1997), before being promoted to the 1st. Class (in 2000), the Exceptional Class (in 2010), and the 2nd. grade in the Exceptional Class (in 2013).

From 2000 to 2007, he directed the Jean Roche Federative Research Institute’s Biology of Cellular Interactions Department in Marseille before becoming Director of the Institute’s Neuroscience department IFR11 from 2008 to 2011.

Since 2008, he has directed the CRN2M Research Centre for Neurobiology and Neurophysiology (which is under the aegis of both the CNRS and the University of Aix- Marseille) in Marseille.

Since 2011, he has also been in charge of the Molecular Biology Department at the Conception Hospital (a public hospital).

Membership of committees responsible for scientific strategy and governance

Alain Enjalbert became a member of the Scientific Committee of the CNRS section specialized in Neurophysiology, Neuro-endocrinology and Behaviour, that of INRA’s Animal Physiology Department (1985-1990) and that of the Cochin Medical Faculty (1990-1993).

He served as President of the CNRS Cellular interactions section (1991-1995) and President of the Scientific Committee of the Higher Regional Council for research and scientific communication in the Provence-Alpes-Côte d’Azur region (1996-1999).

He was a member of the Scientific Committee of the French Foundation for Medical Research (2000-2004) and the Regional Scientific Committee of the French League against Cancer (2000-2005). He subsequently became a member of the University of the Mediterranean’s Scientific Committee and the Faculty of Medicine’s Scientific Committee (2004-2009) before serving as Vice-President of the University of the Mediterranean (2009-2011), and he is currently a member of Aix-Marseille University’s Scientific Committee (since 2012 ) and Vice-President of the Faculty of Medicine’s Scientific Committee (since 2011).

Special Distinctions and Awards

Alain Enjalbert received the Prize for Research in Endocrinology awarded by the FrenchFoundation for Medical Research in 1986.

He became Knight of the French Order of Academic Palms in 2005.

Membership of scientific societies

Alain Enjalbert served as a member of the Board of Administration of the Société des neurosciences (1990-1995)

and is currently President of the French Pituitary Club, which is part of the Société française d’endocrinologie (since 1998).

He is also a member of the International Neuroendocrine Federation’s Strategic Action Committee (since 2010) and served as Vice-President of the French Experimental Neuroendocrinological Society (1996-1999) and President of the French Neuro-endocrinological Society (1999-2002).

He was European Member of the Neuroendocrine Association’s Board of Administration (2004-2009), and became Vice-President (2006-2008) and then President (2008-2010) of the Société française d’endocrinologie. He was recently President of the Permanent Scientific Board of the Société Française d’Endocrinologie (2010-2012)

Editorial Board membership

Alain Enjalbert was a member of the Editorial Board (1989-1993) and subsequently Scientific Editor of the journal Neuroendocrinology from 1993 to the present day. He was Sector Editor of the Journal de physiologie (1989-1993) and Receiving Editor of the Journal of neuroendocrinology (1989-1996). He was also a member of the Editorial Board of the journal Encéphale (1990) and that of Annales d’endocrinologie (2006-2011).

Scientific research

Since the first research work he conducted at the Inserm Neurobiology Unit 109 at Saint Anne’s Hospital in Paris, Alain Enjalbert has always been interested in the mechanisms underlying the transfer and integration of neuro-endocrine information.

Under the leadership of his mentor Claude Kordon, he developed physiological and pharmacological approaches for use on animals and cell cultures, which he used to study the multiple factors involved in hypothalamo-pituitary regulation processes ; in particular, he identified some of the main hypothalamic factors involved in the regulation of prolactin secretion processes.

While undergoing postdoctoral training at Jacques Glowinski’s laboratory at the Collège de France, he studied the G-protein-mediated signal transduction mechanisms at work in the central nervous system. Along with Joël Bockaert and Michel Hamon, he established the existence of serotonin receptors which are positively coupled to adenylate cyclase. He then set up a group to study neuro-hormone receptors and their transduction processes. He and Joël Bockaert established that the D2 dopaminergic receptors are negatively coupled to adenylate, as well as to phospholipase C.

Using these neuro-endocrine systems as models, the members of this group subsequently these neuro-endocrine systems as models, the members of this group subsequently extended their findings to the central nervous system. This approach was first adopted in collaboration with Joël Prémont, focusing on the effects of steroids on dopaminergic receptor binding to adenylate cyclase, and then with Jacques Epelbaum, focusing on the somatostatin receptors. His findings on the mechanisms involved in pituitary receptor binding processes then led Alain Enjalbert to analyze the interactions between transduction cascades and their effects on hormone secretion processes.

He also developed a cross-disciplinary approach by applying these concepts and methods to clinical problems, starting with pituitary adenomas.

In 1993, he launched major restructuring operations in Marseille, which resulted in the creation of a joint research unit, where basic research scientists and clinical specialists belonging to both the CNRS and the University of the Mediterranean were able to work together on a site located north of the Northern Hospital’s Medical Faculty.

After instigating the creation of this unit, Alain Enjalbert established along with Philippe Jaquet that the loss of sensitivity of prolactinomas to dopaminergic analogues was due to the deregulation of both D2 dopaminergic receptor expression and that of components involved in the transduction cascade such as G proteins, as well as to specific transcription factors such as Pit1. In partnership with the pharmaceutical industry, these investigators also developed more efficacious analogues than the drugs available at that time, by specifically targeting somatostatin and dopamine receptor sub-types. In parallel, they investigated the interactions between the transduction cascades induced by G-protein coupled receptors and growth factor receptors. In their studies on human tumours and inducible cell line models, they described the central role played in hormonal hypersecretion anomalies by the activation of the Map kinase cascade in the presence of the constitutively active mutated Gsa sub-unit oncogene gsp, along with the over-expression of the wild-type Gsa sub-unit. To account for this overexpression, these authors established that the GNAS1 gene coding for Gsa is subject to a parental imprinting process in the pituitary, contrary to what occurs in many other tissues. They used two different approaches to study the transcription factors involved. In the first place, it was proposed to analyze the mutations responsible for combined pituitary deficiencies in humans, in partnership with the Conception Hospital’s Laboratory of Biochemistry in Marseille. Secondly, it was proposed to investigate the expression of these factors in pituitary adenomas. It turned out that these transcription factors play a hitherto unsuspected role in controlling the proliferation or apoptosis of these adenomas. It was then proposed to study the use of dominant negative mutants of these factors to develop gene therapy treatments for resistant adenomas. Using a similar approach with re-expressed SST2 receptors, Alain Enjalbert and his co-workers then observed not only that adenoma cell cultures showed a similar sensitivity to somatostatin, but also that the somatostatin receptors showed constitutive pro-apoptotic activity, which meant that these authors were responsible for the discovery of tumour-suppressing genes.

The above research was carried out at the Research Centre for Neurobiology and Neurophysiology in Marseille, the CRN2M, which Alain Enjalbert has directed since 1st. January, 2008.

Selected publications
- Enjalbert A, Moss F., Carbonell L., Priam M., Kordon C. Prolactin inhibiting activity of dopamine-free subcellular fractions from rat mediobasal hypothalamus. Neuroendocrinology 24 : 147, 1976.
- Enjalbert A, Bourgoin S, Hamon M, Adrien J, Bockaert J. Post-synaptic serotonin sensitive adenylate cyclasein the central nervous system. I : Development and distribution of serotonin and dopamine sensitive adenylate cyclases in rat and guinea pig brain. Mol Pharmacol 14 : 2, 1978.
- Enjalbert A, Ruberg M, Arancibia S, Fiore L, Priam M, Kordon C. Independent inhibition of prolactinsecretion by dopamine and ?-aminobutyric acid in vitro. Endocrinology 105 : 823, 1979.
- Enjalbert A, Ruberg M, Arancibia S, Priam M, Kordon C. Endogenous opiates block dopamine inhibition of prolactin secretion in vitro. Nature 280 : 595, 1979.
- Enjalbert A, Arancibia S, Ruberg M, Priam M, Bluet-pajot MT, Rotsztejn W, Kordon C. Stimulation of in vitro prolactin release by vasoactive intestinal peptide. Neuroendocrinology 31 : 200, 1980.
- Enjalbert A, Bockaert J. Pharmacological characterization of the D2-dopamine receptor negatively coupled with adenylate cyclase in rat anterior pituitary. Mol Pharmacol 23 : 576, 1983.
- Moyse E, Le Dafniet M, Epelbaum J, Pagesy P, Peillon F, Kordon C, Enjalbert A. Somatostatin receptors in human growth hormone and prolactin secreting pituitary adenomas. J Clin Endocr Metab 61 : 98, 1985.
- Enjalbert A, Sladeczek F, Guillon G, Bertrand P, Shu C, Epelbaum J, Garcia-Sainz JA, Jard S, Lombard C, Kordon C, Bockaert J. Angiotensin II and dopamine modulate both cAMP and inositol phosphate production in anterior pituitary cells. Involvement in prolactin secretion. J Biol Chem 25 : 4071-5, 1985.
- Journot L, Homburger V, Pantaloni C, Priam M, Bockaert J, Enjalbert A. An IAP-sensitive G protein is involved in dopamine inhibition of angiotensin and TRH stimulated inositol phosphate production in anterior pituitary cells. J Biol Chem 262 : 15106-10, 1987.
- Enjalbert A, Musset F, Chénard C, Priam M, Kordon C, Heisler S. Dopamine inhibits prolactin secretion stimulated by the calcium channel agonist BAY-8644 through a pertussis toxin sensitive G protein in anterior pituitary cells. Endocrinology 123 : 406-12, 1988.
- Maus M, Bertrand P, Drouva S, Rasolonjanahary R, Kordon C, Glowinski J, Prémont J, Enjalbert A. Differential effects of estradiol on D1 and D2 dopamine sensitive adenylate cyclase in anterior pituitary cells and striatal neurons in primary culture. J Neurochem 52 : 410-8, 1989.
- Pellegrini I, Rasolonjanahary R, Gunz G, Bertrand P, Delivet S, Jedynak GP, Kordon C, Peillon F, Jaquet P, Enjalbert A. Resistance to bromocriptine in prolactinomas. J Clin Endocr Metab 69 : 500-9, 1990.
- Enjalbert A, Guillon G, Mouillac B, Audinot V, Rasolonjanahary R, Kordon C, Bockaert J. Dual mechanism of inhibition by dopamine of basal and TRH stimulated inositol phosphate production in anterior pituitary cells. Evidence for an inhibition not mediated by voltage dependent Ca2+ channels. J Biol Chem 265 : 18816-22, 1990.
- Audinot V, Rasolonjanahary R, Bertrand P, Priam M, Kordon C, Enjalbert A. Involvement of protein kinaseC in coupling of AII receptors with cyclic AMP production in anterior pituitary cells. Endocrinology 129 : 2231-9, 1991.
- Chuang TT, Caccavelli L, Kordon C, Enjalbert A. Protein kinase C regulation of prolactin gene expression in lactrotroph cells : involvement in dopamine inhibition. Endocrinology 132 : 832-8, 1993.
- Pellegrini-Bouiller I, Morange-Ramos I, Barlier A, Gunz G, Figarella-Branger D, Cortet-Rudelli C, Grisoli F, Jaquet P, - Enjalbert A. Pit-1 gene expression in human lactotroph and somatotroph pituitary adenomas is correlated to D2 receptor gene expression. J Clin Endocr Metab 81 : 3390-6, 1996.
- Barlier A, Pellegrini-Bouiller I, Gunz G, Zamora AJ, Jaquet P, Enjalbert A. Impact of gsp oncogene on the expression of genes coding for Gsalpha, Pit-1, Gi2alpha, and SSTR2 in human somatotroph adenomas. Involvement in octreotide sensitivity. J Clin Endocr Metab 84 : 2759-65, 1999.
- Jaquet P, Ouafik LH, Saveanu A, Gunz G, Fina F, Dufour H, Culler MD, Moreau JP, Enjalbert A. Quantitative and functional expression of somatostatin-receptor subtypes in human prolactinomas. J Clin Endocr Metab 84 : 3268-3276, 1999.
- Hayward BE, Barlier A, Korbonits M, Grossman AB, Jaquet P, Enjalbert A, Bonthron DT. Imprinting of the Gsalpha gene GNAS1 in the pathogenesis of acromegaly. J Clin Invest 107:R31-36, 2001.
- Lamolet B, Pulichino AM, Lamonerie T, Gauthier Y, Brue T, Enjalbert A, Drouin J. A pituitary cellrestricted T-box factor, TPIT, activates POMC transcription in cooperation with PITX homeoproteins. Cell 104 : 849-59, 2001.
- Vallette-Kasic S, Pellegrini-Bouiller I, Sampieri F, Gunz G, Diaz A, Radovick S, Enjalbert A, Brue T. Combined pituitary hormone deficiency due to the F135C human Pit-1 gene mutation : functional and structural correlates. Mol Endocrinol 15 : 411-20, 2001.
- Junoy B, Maccario H, Mas JL, Enjalbert A, Drouva SV. Proteasome implication in TPA- and GnRH-induced selective down regulation of protein kinase C isoenzymes (alpha, epsilon, zeta) in aT3-1 and LbT2 gonadotrope cell lines. Endocrinology 143 : 1386-1403, 2002.
- Quentien MH, Manfroid I, Muller M, Moncet D, Grino M, Gunz G, Enjalbert A, Pellegrini I. Pitx factors are involved in basal and hormone-regulated activity of the human prolactin promoter. J Biol Chem 277 : 44408-16, 2002.
- Saveanu A, Lavaque E, Gunz G, Barlier A, Kim S, Taylor JE, Culler MD, Enjalbert A, Jaquet P. Demonstration of enhanced potency of a chimeric somatostatin-dopamine molecule, BIM-23A387, in suppressing GH and PRL secretion from human pituitary somatotroph adenoma cells. J Clin Endocrinol Metab87 : 5545-51, 2002.
- Romano D, Magalon K, Ciampini A, Talet C, Enjalbert A, Gerard C. Differential involvement of the Ras and Rap1 small GTPases n vasoactive intestinal and pituitary adenylyl cyclase activating polypeptides control of the prolactin gene. J Biol Chem 278 : 51386-94, 2003.
- Fombonne J, Reix S, Rasolonjanahary R, Danty E, Thirion S, Laforge-Anglade G, Bosler O, Mehlen P, Enjalbert A, Krantic S. EGF triggers an original caspase-independent pituitary cell death with heterogeneous phenotype. Mol Biol Cell 15 : 4938-48, 2004.
- Krantic S, Goddard I, Saveanu A, Giannetti N, Fombonne J, Cardoso A, Jaquet P, Enjalbert A. Novel modalities of somatostatin actions. Eur J Endocrinol 152 : 1-14, 2004.
- Gautron JP, Gras C, Enjalbert A. Molecular polymorphism of native gonadotropin-releasing hormone (GnRH) is restricted to mammalian GnRH and [hydroxyproline9]GnRH in the developing rat brain. Neuroendocrinology 81 : 69-86, 2005.
- Vallette-Kasic S, Brue T, Pulichino AM, Gueydan M, Barlier A, David M, Nicolino M, Malpuech G, Dechelotte P, Deal C, Van Vliet G, De Vroede M, Riepe FG, Partsch CJ, Sippell WG, Berberoglu M, Atasay B, De Zegher F, Beckers D, Kyllo J, Donohoue P, Fassnacht M, Hahner S, Allolio B, Noordam C, Dunkel L, Hero M, Pigeon B, Weill J, Yigit S, Brauner R, Heinrich JJ, Cummings E, Riddell C, Enjalbert A, Drouin J. Congenital isolated adrenocorticotropin deficiency : an underestimated cause of neonatal death, explained by TPIT gene mutations. J Clin Endocrinol Metab 90 : 1323-31, 2005.
- Pellegrini I, Roche C, Quentien MH, Ferrand M, Gunz G, Thirion S, Bagnis C, Enjalbert A, Franc JL. Involvement of the pituitary-specific transcription factor Pit-1 in somatolactotrope cell growth and death : an approach using dominant-negative Pit-1 mutants. Mol Endocrinol 20 : 3212-27, 2006.
- Quentien MH, Barlier A, Franc JL, Pellegrini I, Brue T, Enjalbert A. Pituitary transcription factors : from congenital deficiencies to gene therapy. J Neuroendocrinol 18 : 633-42, 2006.
- Romano D, Magalon K, Pertuit M, Rasolonjanahary R, Barlier A, Enjalbert A, Gerard C. Conditional overexpression of the wild type Gsalpha as the gsp oncogene initiates chronic extracellularly regulated kinase 1/2 activation and hormone hypersecretion in pituitary cell lines. Endocrinology 148 : 2973-83, 2007.
- Acunzo J, Thirion S, Roche C, Saveanu A, Gunz G, Germanetti AL, Couderc B, Cohen R, Figarella-Branger D, Dufour H, Brue T, Enjalbert A, Barlier A. Somatostatin receptor sst2 decreases cell viability and hormonal hypersecretion and reverses octreotide resistance of human pituitary adenomas. Cancer Res 68 : 10163-70, 2008.
- Pertuit M, Barlier A, Enjalbert A, Gerard C. Signalling pathway alterations in pituitary adenomas : involvement of Gsalpha, cAMP and mitogen-activated protein kinases. J Neuroendocrinol. 2009 Nov ;21(11):869-77
- Acunzo J, Roche C, Defilles C, Thirion S, Quentien MH, Figarella-Branger D, Graillon T, Dufour H, Brue T, Pellegrini I, Enjalbert A, Barlier A.Inactivation of PITX2 transcription factor induced apoptosis of gonadotroph tumoral cells. Endocrinology. 2011 Oct ;152(10):3884-92
- Reynaud R, Castinetti F, Galon-Faure N, Albarel-Loy F, Saveanu A, Quentien MH, Jullien N, Khammar A, Enjalbert A, Barlier A, Brue T. [Genetic aspects of growth hormone deficiency.] Arch Pediatr. 2011 Jun ;18(6):696-706
- Ann N Y, Cuny T, Gerard C, Saveanu A, Barlier A, Enjalbert A. Physiopathology of somatolactotroph cells : from transduction mechanisms to cotargeting therapy. Acad Sci. 2011 Mar ;1220(1):60-70
- Herman JP, Jullien N, Guillen S, Enjalbert A, Pellegrini I, Franc JL. Research Resource : A Genome-Wide Study Identifies Potential New Target Genes for POU1F1. Mol Endocrinol. 2012 May ;
- Roche C, Rasolonjanahary R, Thirion S, Goddard I, Fusco A, Figarella-Branger D, Dufour H, Brue T, Franc JL, Enjalbert A, Barlier A. Inactivation of transcription factor Pit-1 to target tumoral somato-lactotroph cells. Hum Gene Ther. 2012 Jan ;23(1):104-14
- Cuny T, Pertuit M, Sahnoun-Fathallah M, Daly A, Occhi G, Odou MF, Tabarin A, Nunes ML, Delemer B, Rohmer V, Desailloud R, Kerlan V, Chabre O, Sadoul JL, Cogne M, Caron P, Cortet-Rudelli C, Lienhardt A, Raingeard I, Guedj AM, Brue T, Beckers A, Weryha G, Enjalbert A, Barlier A. Genetic analysis in young patients with sporadic pituitary macroadenomas : besides AIP don’t forget MEN1 genetic analysis. Eur J Endocrinol. 2013 Mar 15 ;168(4):533-41.
- Cuny T, Barlier A, Enjalbert A. Endocrine disorders. Chapter book "In vivo models for drug" discovery" by Wiley-­‐VCH Verlag GmbH & Co. Kga, 2013 (in press).

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