Characterization of cDNA and genomic clones encoding the precursor to rat hypothalamic growth hormone-releasing factor

Growth hormone-releasing factor (GHRF) is a hypothalamic peptide which positively regulates the synthesis and secretion of growth hormone in the anterior pituitary. The amino-acid sequence of a 43-residue GHRF peptide isolated from rat hypothalamus was recently determined¹. Immunocytochemical techniques have been used to localize GHRF-containing cell bodies and nerve fibres largely to the medial-basal region of the rat hypothalamus². The rat has also been used extensively as an animal model to study the effects of GHRF on growth hormone synthesis^3,4 and secretion^5,6 and on somatic growth⁷. To pursue questions concerning the biosynthesis of GHRF, the expression of the ghrf gene, and its regulation in the hypothalamus by neural and hormonal influences, we have now isolated and characterized both complementary DNA and genomic clones encoding rat hypothalamic GHRF. The rat ghrf gene spans nearly 10 kilobases (kb) of rat genomic DNA, contains 5 exons and encodes a 104-amino-acid precursor to the rat GHRF peptide. Comparison with previously characterized human ghrf cDNA ^8,9 and genomic¹⁰ clones has allowed patterns of conservation of amino-acid and nucleotide sequences between the human and rat GHRFs to be determined.