Characterization of cDNA for precursor of human luteinizing hormone releasing hormone

Human reproduction is controlled by the hypothalamic-pituitary-gonadal axis laid down early in fetal development. Luteinizing hormone releasing hormone (LHRH), also termed gonadotropin releasing hormone (GnRH), is a decapeptide ^1,2 and is a key molecule in this control circuit. It is produced by hypothalamic neurones, secreted in a pulsatile manner into the capillary plexus of the median eminence and effects the release of luteinizing hormone and follicle stimulating hormone from gonadotropic cells in the anterior pituitary³. The peptide may have further functions, including behavioural ones⁴, as LHRH or LHRH-like immunoreactivity has been found in gonadal tissue^5,6, placenta^7,8 and the central nervous system^9,10, and exogenously administered LHRH is shown to affect behaviour^11,12. To investigate the biosynthesis of LHRH, we have now isolated cloned genomic and cDNA sequences encoding the precursor form of LHRH, the existence of which had been suggested from Chromatographic studies of hypothalamic^8,13 and placental⁸ extracts. These DNA sequences code for a protein of 92 amino acids in which the LHRH 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^14-16 and amidation¹⁷ of the carboxy-terminal of LHRH.