IDENTIFICATION OF HUMAN GROWTH HORMONE-RELEASING HORMONE-RECEPTOR SPLICING VARIANTS

The expression pattern of the receptor for human GHRH (hGHRHr) was investigated in normal human tissues and in pituitary and ovarian tumors by reverse transcription-polymerase chain reaction. Three transcriptional variant forms of the hGHRHr were found to be expressed in the normal pituitary and in GH-secreting pituitary tumors. Form a is identical ta the previously reported hGHRHr, whereas forms b and c are not described in the literature. Form b and c are predicted to be transcribed into two truncated proteins. We amplified genomic DNA using primers designed from the complementary DNA of hGHRHr. A 2-kilobase genomic DNA fragment was cloned that contains part of the hGHRHr gene consisting of two exons, e864 and e934, separated by three introns, i863, i933, and i1025. Alternative splicing of i1025 was responsible for three variant forms of hGHRHr. Nonsecreting pituitary tumors showed an abnormal ex expression of the hGHRHr, probably due to alternative usage of exons at the 5'-end of the gene, although they also expressed the three variant forms. No hGHRHr expression was identified in a human mammosomatotroph cell line insensitive to GHRH, in normal human liver or ovary, or in various human ovarian tumors.