SPLICING VARIANTS OF THE HUMAN GROWTH-HORMONE MESSENGER-RNA - DETECTION IN PITUITARY, MONONUCLEAR-CELLS AND DERMAL FIBROBLASTS

The human growth hormone/human chorionic somatomammotropin (hGH/hCS) gene cluster contains five genes: hGH-N, hGH-V, hCS-A, hCS-B, and hCS-L. In this study, the nature of splicing products of their primary transcripts (except hCS-L) was analyzed by nuclease mapping as well as by reverse transcription-polymerase chain reaction (RT-PCR) experiments. All the previously described hGH-N mRNAs encoding the normal 22-K growth hormone, the 20-K variant as well as a transcript lacking the third exon were found in pituitary tissue and in transiently transfected human 293-S eels. In addition, splicing products lacking either exons 3 and 4 or exons 2, 3 and 4 were found in both tissues. In accordance to previously reported data,the hGH-V, the hCS-A and the hCS-B genes which are expressed in placental tissue give rise to the 22-K mRNA but not to 20-K mRNA. Furthermore, no hCS mRNA arising from skipping of exon 3 was present, whereas mRNAs arising from ligation of exon 2 to exon 5 and of exon 1 to exon 5 were clearly detectable. The various hGH cDNAs were expressed in vivo and screened for lactogenic activity. Only the 22-K and the 20-K variant were active in this assay. All of the hGH-N-derived differentially processed RNAs were found in cell lines of lymphoid (Hut-78) and of myelomonocytic type (U937), which had been recently described to secrete growth hormone. Interestingly, RT-PCR analysis allowed the determination of hGH-N transcripts in dermal fibroblasts. This finding underlines the importance of growth hormone in influencing immune system development and further suggests possible autocrine/paracrine regulatory loops in skin tissue.