Discovery of a gene involved in the development of puberty

June 17 2009

Researchers in Inserm unit 693 (Inserm-Université Paris Sud 11 Mixed Unit) at the Hôpital de Bicêtre have shown, for the first time, the role of a hormone secreted by the hypothalamus, GnRH1 (gonadotropin releasing hormone 1) in the triggering of human puberty. Thanks to these studies, the researchers have begun to better understand the genetic control of pubertal development.

This study is published today in the New England Journal of Medicine.

Puberty is an important stage in maturity and the perpetuation of the species. It involves bodily, physiological and psychological changes. At the level of the body, it corresponds to the activation of the hypothalamic-hypophyseal function, leading to the complete development of the sex characteristics, with the acquisition of final height, reproductive function and fertility.

Many factors come into play to control these complex functions during puberty and then throughout adult life. Among these, GnRH (gonadotropin releasing hormone) plays a major role. GnrH is a neurohormone controlling the synthesis and release of 2 pituitary hormones (LH and FSH) responsible for the production of ovarian and testicular sex hormones. In this study, the Inserm scientists observed that a mutation in the gene coding for GnRH was involved in a form of congenital hypogonadotrophic hypogonadism, a disease in which the triggering of puberty is absent or blocked. This syndrome, which affects nearly one person in 8,000 is therefore a result of a defect in hypothalamic-hypophyseal control leading to an insufficient production of sex hormones and is characterised by a complete or partial absence of development of the primary and secondary sexual characteristics during puberty.

The abnormality discovered which has an autosomal recessive mode of inheritance, concerns chromosome 8 and is the result of the insertion of an adenine base in the terminal part of the gene. Whereas the normal GnRH protein comprises 92 amino-acids, the mutant version only contains 42.

In these patients, the administration of GnRH made it possible to restore the endogenous manufacture of luteinizing hormone (LH). “This restoration allowed us to show that pituitary cells function normally in these individuals. There is no other GnRH-independent route for the triggering of puberty. Like a set of gears in which one is jammed, if GnRH does not play its part, the whole mechanism of puberty is modified,” declared the Inserm researchers Jacques Young and Anne Mantel, who performed this study.

These results therefore definitively demonstrate the crucial role of GnRH in the human species where it ensures the same role as in all mammals during evolution.

This study associated with the other research currently carried out in this field by Inserm unit 693 will improve our understanding of the physiology of the neuroendocrine control of puberty and enable us to better characterise the genetic transmission and hormonal mechanism of the associated diseases. “We can treat these causes of infertility,” added Jacques Young. Thanks to these new results, the researchers hope at the same time to improve screening and genetic counselling and be able to propose appropriate hormone management.

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Researcher’s contact details

Jacques Young
Inserm Unit 693 “récepteurs stéroidiens: physiopathologie endocrinienne et métabolique”
Phone: 01 45 21 37 05

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