Splicing variants of the human growth hormone mRNA: 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-B, and hCS-L. In this study, the nature of splicing products of their primary transcripts (except hCH-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 pituitary tissue and in transiently transfected human 293-S cells. In addition, splicing products lacking either exons 3 and 4 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.
Palmetshofer
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Institute of Biochemistry, Vienna Biocenter, University of Vienna, Austria.
Zechner
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Luger
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Barta
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D017398:Alternative Splicing; D001483:Base Sequence; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D005091:Exons; D005347:Fibroblasts / Q000737:chemistry*; D015870:Gene Expression; D013006:Growth Hormone / Q000235:genetics* / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000737:chemistry*; D008969:Molecular Sequence Data; D010902:Pituitary Gland / Q000737:chemistry*; D010928:Placental Lactogen / Q000235:genetics / Q000494:pharmacology; D016133:Polymerase Chain Reaction; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000032:analysis*; D017421:Sequence Analysis; D012867:Skin; D014162:Transfection
D012333:RNA, Messenger; D013006:Growth Hormone; D010928:Placental Lactogen