This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Boguszewski, C. L. Articles by Carlsson, B. Search for Related Content PubMed PubMed Citation Articles by Boguszewski, C. L. Articles by Carlsson, B.

Cloning of Two Novel Growth Hormone Transcripts Expressed in Human Placenta¹

Research Centre for Endocrinology and Metabolism (C.L.B., P-A.S., L.M.S.C., B.C.), Department of Internal Medicine, Department of Physiology and Pharmacology (T.J.), Sahlgrenska University Hospital, Göteborg, Sweden; Research Centre for Developmental Medicine and Biology (R.C.), University of Auckland, New Zealand

Address all correspondence and requests for reprints to: Björn Carlsson, Research Centre for Endocrinology and Metabolism-Sahlgrenska University Hospital, Gröna Stråket 8-S-413 45, Göteborg, Sweden. E-mail: bjorn.carlsson{at}ss.gu.se

Several isoforms of human GH (hGH) are produced by two related genes expressed in the pituitary (hGH-N) and in the placenta (hGH-V). These genes consist of five exons (denoted 1–5) separated by four introns (denoted A-D). In the present report, two new transcripts of the hGH-V gene are described. The coding region of the hGH-V gene was amplified by RT-PCR using placental complementary DNA as template. DNA sequencing of several clones revealed two novel transcripts. One had a 45-bp deletion caused by the use of an alternative splice acceptor site within exon 3, similar to that in the hGH-N gene, predicting a 20-kDa isoform of hGH-V. The other transcript was generated by the use of an alternative splice donor site causing a 4-bp deletion in the end of exon 4, predicting a 24-kDa protein with 219 amino acids, which we refer to as hGH-V3. The carboxy-terminal sequence of hGH-V3 differs from 22-kDa hGH-V and hGH-V2, the two previously reported transcripts of the hGH-V gene, and does not contain a predicted transmembrane domain as described for hGH-V2. Ligase chain reaction was then used to analyze the possible use of the same splicing pattern in transcripts derived from the other genes of the hGH-gene cluster. Alternatively spliced transcripts encoding the 20-kDa hGH isoform were detected from the hGH-N and hGH-V genes, but not from the human chorionic somatomammotropin-A/B genes. The alternative splicing generating hGH-V3 was only demonstrated in transcripts derived from the hGH-V gene. Using competitive RT-PCR, the expression of hGH-V3 was estimated to be 10% of the hGH-V messenger RNA in full-term normal placentas and in placentas from pathological pregnancies. The 20-kDa hGH-V was detected in two of four full-term normal placentas, whereas a weak signal was observed in one of the pathological placentas. We conclude that the hGH-V primary transcript undergoes alternative splicing pathways generating at least four different messenger RNAs, predicting the expression of different hGH isoforms, including two with a complete sequence divergence in the carboxy-terminus.

This article has been cited by other articles:

				M.-L. Baudet, B. Martin, Z. Hassanali, E. Parker, E. J. Sanders, and S. Harvey Expression, Translation, and Localization of a Novel, Small Growth Hormone Variant Endocrinology, January 1, 2007; 148(1): 103 - 115. [Abstract] [Full Text] [PDF]

				K.-C. Leung, G. Johannsson, G. M. Leong, and K. K. Y. Ho Estrogen Regulation of Growth Hormone Action Endocr. Rev., October 1, 2004; 25(5): 693 - 721. [Abstract] [Full Text] [PDF]

				D. Le Roith, C. Bondy, S. Yakar, J.-L. Liu, and A. Butler The Somatomedin Hypothesis: 2001 Endocr. Rev., February 1, 2001; 22(1): 53 - 74. [Abstract] [Full Text]