EXPRESSION OF THE RAT GROWTH HORMONE-RELEASING HORMONE GENE IN PLACENTA IS DIRECTED BY AN ALTERNATIVE PROMOTER

Growth hormone-releasing hormone (GHRH) is a hypothalamic peptide that plays a critical role in controlling the synthesis and secretion of growth hormone by the anterior pituitary. GHRH has also been detected in other nonneural extrahypothalamic tissues, including rat placenta, although its role in the hormonal control of pregnancy and/or fetal development has not yet been defined. Here we present the isolation and characterization of cDNA clones corresponding to rat placental GHRH. The placental GHRH mRNA codes for a pre-pro-GHRH identical to that found in the hypothalamus, suggesting that the mature placental GHRH is identical to its hypothalamic counterpart. Nevertheless, the placental and the hypothalamic GHRH mRNAs differ in the region corresponding to the untranslated exon 1 because of the use of an alternative promoter in the placenta located 10 kilobases upstream from the hypothalamic promoter. A combined mechanism involving the use of tissue-specific alternative promoters and the differential splicing of exon 1 generates the mature GHRH transcript in placenta and hypothalamus. Multiple transcription initiation sites have been found in the placental GHRH mRNA, which correlates to the lack of a consensus TATA box in the promoter region.