Mouse growth-hormone-releasing hormone: precursor structure and expression in brain and placenta

To pursue questions concerning the regulation of somatic growth in a species amenable to both genetics and germ-line manipulation, we have isolated and characterized a full-length cDNA clone encoding mouse GH-releasing hormone (mGHRH). A GHRH cDNA clone isolated from a mouse placental library contains an open-reading frame of 309 basepairs that predicts a 103 amino acid mouse GHRH precursor protein. The mature mouse GHRH is predicted to be 42 amino acids with a free carboxyl-terminus. Although the mGHRH precursor sequence is clearly related to those determined for rat and human, the mature mGHRH peptide differs at seven of its 42 positions from all previously characterized GHRH peptides. RNA blot analysis of mouse tissues indicates that the mature 750 nucleotide mGHRH mRNA is found in hypothalamus and placenta, while testis contains a larger GHRH-related transcript. In situ hybridization analysis of GHRH gene expression in the mouse brain indicates that GHRH mRNA is localized predominantly to the arcuate nucleus of the hypothalamus. In the placenta, GHRH mRNA levels are developmentally regulated and peak on days 16-17 of gestation. GHRH mRNA is localized predominantly to trophoblast giant cells and to cytotrophoblasts of the placental labyrinth.