• OMIM 152760
  • Located at chromosome 8p21-p11.2
  • Encodes gonadotropin-releasing hormone 1 (GnRH1, a.k.a. luteinizing-hormone releasing hormone, LHRH), which is a key molecule in the hypothalamic-pituitary-gonadal axis that controls human reproduction.
  • GnRH1 is secreted as a decapeptide by hypothalamic neurons into the capillary plexus of the median eminence in a pulsatile manner. It then acts on gonadotrope cells of the anterior pituitary to stimulate the release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH).
  • GNRH1 comprises 3 exons and the corresponding mRNA (NM_000825.3) encodes a 92 amino acid preprohormone, in which the GnRH1 decapeptide is preceded by a signal peptide of 23 amino acids and followed by a Gly-Lys-Arg sequence as expected for enzymatic cleavage of the decapeptide from its precursor and amidation of the carboxy-terminal of GnRH (Seeburg and Adelman 1984).

Human genetics

  • Despite GNRH1 being an obvious candidate gene for GnRH deficiency, few mutations in this gene have been identified in patients with congenital hypogonadotropic hypogonadism (CHH).
  • CHH-associated GNRH1 mutations have been identified in both the homozygous state (autosomal recessive CHH inheritance) (Bouligand, Ghervan et al. 2009) and the heterozygous state (probable oligogenic inheritance) (Chan, de Guillebon et al. 2009).
  • These mutations are associated with the normosmic form of CHH.


Bouligand, J., C. Ghervan, et al. (2009). "Isolated familial hypogonadotropic hypogonadism and a GNRH1 mutation." N Engl J Med 360(26): 2742-2748.

Chan, Y. M., A. de Guillebon, et al. (2009). "GNRH1 mutations in patients with idiopathic hypogonadotropic hypogonadism." Proc Natl Acad Sci U S A 106(28): 11703-11708.

Seeburg, P. H. and J. P. Adelman (1984). "Characterization of cDNA for precursor of human luteinizing hormone releasing hormone." Nature 311(5987): 666-668.

 Last updated on 29/05/2018 at 09:52