The Rare Genetic Steroid Disorders Consortium
Participating Clinical Centers
Logo of the University of Lyon

University of Lyon

Lyon, France

Yves Morel, M.D., Ph.D
Email: morel@lyon.inserm.fr

Maguelone Forest, M.D., Ph.D.

Jacques Simard, Ph.D. (Université Laval, Quebec)

Contact Information:

Research and Academic:

Phone: 011 33 4 72 38 58 50

About Us:

For over 30 years, our group in Lyon, founded by Dr Jean Bertrand upon his return from a fellowship at Johns Hopkins University, has been involved in the development of techniques for measuring steroid hormones in order to apply them to the study of fetal and infant endocrinology, which was quite unknown at the time Dr. Bertrand began to pursue these goals. Dr Maguelone Forest, one his earliest fellows, pursued this path of research with remarkable success. She was among the first in the world to develop specific and sensitive RIAs for steroid hormones. The first and most important application was to show that, contrary to what was thought at that time, an activation of the hypothalamo-pituitary gonadal axis (HHG) occurs after birth (now called "mini-puberty"). This activation of the HHG axis in boys does not last very long and by 6 months of life steroid hormones have returned to prepubertal levels. The role of this mini-puberty is not totally understood, but is certainly involved in the growth of the phallus, and likely also in post-natal imprinting of the brain. Dr Forest had described all the ontogenic patterns of steroid hormones in infancy, an important basis for making specific diagnosis in various pathologies.

The main model that was studied in our growing group was related to hormone steroid biosynthesis in gonads and adrenals, in particular congenital adrenal hyperplasia (CAH). Dr Forest and co-workers were pioneers in the prenatal diagnosis of CAH by measuring steroid hormones in the amniotic fluid.

Dr Morel and his group have developed the genotyping of all disorders of steroid hormone biosynthesis. As of now, genotyping has been performed for 21-Hydroxylase deficiency, in 11b-Hydroxylase deficiency, aldosynthase deficiency, in 3b-HSD deficiency, 17a-OH/17,20 lyase deficiency, congenital adrenal lipoid deficiency, and 17b-HSD deficiency. Our close collaboration with Dr Jacques Simard (Québec, Canada) enabled us to describe the first mutation in 3b-HSD deficiency and to determine almost all 3b-HSD mutations and the functional consequences.

In France, our group is considered as the reference laboratory for this disease (measuring specifically steroids in affected infants/children and detecting heterozygotes using the 21-Deoxy response to an ACTH test). All French clinic patients (and more from different countries) have been genotyped by Dr Morel's group. We conduct genetic counselling for 21-Hydrox deficiency based on family genotyping, prenatal diagnosis, and detection of heterozygotes throughout France based on collaboration with all French pediatricians and geneticians. Thus, we have built a true network of collaborators, which includes clinicians, geneticians and pediatric urologists (specially Dr P. Mouriquand and Dr C. Fékété), throughout France.

Useful Links

The Univeristé Leval Web Site

Current Clinical Trials:

Trial information is under development - please check back for updates!

Publications:

  1. Morel Y, Albaladejo V, Bouvier J, Andre J 1982 Inhibition by 17 b-estradiol of the growth of the rat pituitary transplantable tumor MtF4. Cancer Res 42:1492-7
  2. Morel Y, Picado-Leonard J, Wu DA, Chang CY, Mohandas TK, Chung B, Miller WL 1988 Assignment of the functional gene for human adrenodoxin to chromosome 11q13-qter and of adrenodoxin pseudogenes to chromosome 20cen-q13.1. Am. J. Hum. Genet. 43:52-59
  3. Morel Y, André J, Uring-Lambert B, Hauptmann G, Bétuel H, Tosi M, Forest MG, David M, Bertrand J, Miller WL 1989 Rearrangements and point mutations of P450c21 genes are distinguished by five restriction endonuclease haplotypes identified by a new probing strategy in 57 families with congenital adrenal hyperplasia. J. Clin. Invest. 83:527-536
  4. Morel Y, David M, Forest MG, Bétuel H, Hauptmann G, André J, Bertrand J, Miller WL 1989 Gene conversions and rearrangements cause discordance between inheritance of forms of 21-hydroxylase deficiency and HLA types. J. Clin. Endocrinol. Metab. 68:592-599
  5. Morel Y, Bristow J, Gitelman SE, Miller WL 1989 Transcript encoded on the opposite strand of the human 21-hydroxylase/C4 locus. Proc. Natl. Acad. Sci. USA. 86:6582-6586
  6. Morel Y, Miller WL 1991 Clinical and molecular genetics of congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Adv. Hum. Genet. 20:1-68
  7. Rhéaume E, Simard J, Morel Y, Mebarki F, Zachman M, Forest MG, New MI, Labrie F 1992 Congenital adrenal hyperplasia due to a homozygous nonsense mutation in the type II 3ß-Hydroxysteroid dehydrogenase gene. Nature Genet 1:239-245
  8. Sanchez R, Mébarki F, Rheaume E, Laflamme N, Forest MG, Bey-Omar F, David M, Morel Y, Labrie F, Simard J 1994 Functional characterization of the novel L108W and P186L mutations detected in the type II 3 beta-hydroxysteroid dehydrogenase gene of a male pseudohermaphrodite with congenital adrenal hyperplasia. Hum Mol Genet 3:1639-1645
  9. Mébarki F, Sanchez R, Rhéaume E, Laflamme N, Simard J, Forest MG, Bey-Omar F, David M, Labrie F, Morel Y 1995 Nonsalt-losing male pseudohermaphroditism due to the novel homozygous N100S mutation in the type II 3ß-hydroxysteroid dehydrogenase (HSD3B2) gene. J Clin Endrocrinol Metab 80:2127-2134
  10. Portrat-Doyen S, Tourniaire J, Richard O, Mulatero P, Aupetit-Faisant B, Curnow KM, Pascoe L, Morel Y 1998 Isolated aldosterone synthase deficiency caused by simultaneous E198D and V386A mutations in the CYP11B2 gene. J Clin Endocrinol Metab 83:4156-61
  11. Chabre O, Portrat-Doyen S, Vivier J, Bachelot I, Liakos P, Labat-Moleur F, Chambaz E, Morel Y, Defaye G 2000 Bilateral laparoscopic adrenalectomy for CAH with severe hypertension, resulting from two novel mutations in splice donor sites of CYP11B1. J Clin Endocrinol Metab 85:4060-4068
  12. Portrat S, Mulatero P, Curnow KM, Chaussain JL, Morel Y, Pascoe L 2001 Deletion hybrid genes, due to unequal crossing over between CYP11B1 (11b-Hydroxylase) and CYP11B2(aldosterone synthase) cause steroid 11b-hydroxylase deficiency and congenital adrenal hyperplasia. J Clin Endocrinol Metab 86:3197-201.
  13. .Morel Y, Rey R, Teinturier C, Nicolino M, Michel-Calemard L, Mowszowicz I, Jaubert F, Fellous M, Chaussain JL, Chatelain P, David M, Nihoul-Fekete C, Forest MG, Josso N 2002 Aetiological diagnosis of male sex ambiguity: a collaborative study. Eur J Pediatr 161:49-59.
  14. Forest MG, Cathiard AM, Bertrand J. Total and unbound testosterone levels in the newborn, and in normal and in hypogonadal children : use of a sensitive radioimmunoassay for testosterone. J Clin Endocrinom Metab 1973;36:1132-1142.
  15. Forest MG, Cathiard AM, Bertrand J. Evidence of testicular activity in early infancy. J Clin Endocrinol Metab 1973;37:148-151.
  16. Forest MG, Sizonenko PC, Cathiard AM, Bertrand J. Hypophyso-gonadal function in human during the first year of life. I. Evidence for testicular activity in early infancy. J Clin Invest 1974;53:819-828.
  17. Forest MG, Cathiard AM. Pattern of testosterone and androstenedione during the first month of life: evidence for testicular activity at birth. J Clin Endocrinol Metab 1975;41:977-980.
  18. Forest MG. Pattern of the response of testosterone and of its precursors to human chorionic gonadotropin stimulation in relation to age in infants and children. J Clin Endocrinol Metab 1979;49:132-137.
  19. Saez JM, Forest MG. Kinetics of human chorionic gonadotropin-induced response of the human testis. I. Plasma testosterone. Implications for human chorionic gonadotropin stimulation test. J Clin Endocrinol Metab 1979;49:132-137.
  20. Forest MG, Lecoq A, Saez JM. Kinetics of the human chorionic gonadotropin-induced response of the human testis. II. Plasma 17a-Hydroxyprogesterone, 4-androstenedione, estrone and 17ß-estradiol. Evidence for the action of human chorionic gonadotropin on intermediate enzymes implicated in steroid biosynthesis. J Clin Endocrinol Metab 1979;49:284-291.
  21. Forest MG, David M, Lecoq A, Jeune M, Bertrand M. Kinetics of the hCG-induced steroidogenic response of the human testis. III. Studies in children of the plasma levels of testosterone and hG: rationale for testicular stimulation test. Ped Res 1980;14:819-824.
  22. Forest MG, de Peretti E, Lecoq A, Cadillon E, Zabot MT, Thoulon JM. Concentration of 14 steroid hormones in human amniotic fluid of mid-pregnancy. J Clin Endocrinol Metab 1980;51:816-823.
  23. Forest MG, Lecornu M, de Peretti E. Familial male pseudohermaphroditism due to 17-20 desmolase deficiency. I. in vitro endocrine studies. J Clin Endocrinol Metab 1980;50:826-833.
  24. David M, Forest MG. Prenatal treatment of congenital adrenal hyperplasia resulting from 21-hydroxylase deficiency. J Pediatr 1984;105(5):799-803.
  25. Forest MG. Pitfalls in prenatal diagnosis of 21-hydroxylase deficiency by amniotic fluid steroid analysis? A six years experience in 102 pregnancies at risk. Ann N Y Acad Sci 1985;458:130-47.
  26. Rohmer V, Barbot N, Bertrand P, Nahoul K, Bigorgne JC, Forest MG. A case of male pseudohermaphroditism due to 17 alpha-hydroxylase deficiency and hormonal profiles in the nuclear family. J Clin Endocrinol Metab 1990;71(2):523-9.
  27. Forest MG, David M, Morel Y. Prenatal diagnosis and treatment of 21-hydroxylase deficiency. J Steroid Biochem Mol Biol 1993;45(1-3):75-82.
  28. Brunelli VL, Chiumello G, David M, Forest MG. Adrenarche does not occur in treated patients with congenital adrenal hyperplasia resulting from 21-hydroxylase deficiency. Clin Endocrinol (Oxf) 1995;42(5):461-6.
  29. Forest MG, Morel Y, David L. Prenatal treatment of congenital adrenal hyperplasia. Trends Endocrinol Metab 1998;9:284-289.
  30. Joint LWPES/ESPE CAH Working Group CONSENSUS: Consensus Statement on 21-hydroxylase deficiency from the Lawson Wilkins Pediatric Endocrine Society and the European Society for Paediatric Endocrinology. Dr. Maguelone Forest was a participant in the consensus meeting. J Clin Endocrinol Metab 2002;87:4048-4053