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This Article Full Text Full Text (PDF) All Versions of this Article: 287/3/E566    most recent 00110.2004v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via ISI Web of Science (6) Citing Articles via Google Scholar Google Scholar Articles by Iida, K. Articles by Thorner, M. O. Search for Related Content PubMed PubMed Citation Articles by Iida, K. Articles by Thorner, M. O.

Regulation of full-length and truncated growth hormone (GH) receptor by GH in tissues of lit/lit or bovine GH transgenic mice

¹Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Virginia, Charlottesville, Virginia 22908; and ²Edison Biotechnology Institute and ³Department of Biomedical Sciences, College of Osteopathic Medicine, Ohio University, Athens, Ohio 45701

Submitted 5 March 2004 ; accepted in final form 25 May 2004

Two truncated isoforms of growth hormone (GH) receptor (GHR) were identified in mice and in humans. The proteins encoded by these isoforms lack most of the intracellular domain of the GHR and inhibit GH action in a dominant negative fashion. We have quantified the mRNAs encoding the GHR isoforms in mouse tissues by use of real-time RT-PCR and examined the effect of GH excess or deficiency on regulation of mRNA levels of the GHR isoforms in vivo. In the liver, the truncated GHR mRNAs (mGHR-282 and mGHR-280) were 0.5 and <0.1%, respectively, the level of full-length GHR (mGHR-fl). In skeletal muscle, the values were 2–3 and 0.1–0.5% of mGHR-fl, respectively, and in subcutaneous fat, the values were 3–5 and 0.1–0.5% of mGHR-fl, respectively. The bovine GH transgenic mice showed a significant increase of mGHR-fl in liver but a significant decrease in skeletal muscle, with no difference in subcutaneous fat when compared with control mice. The lit/lit mice showed a significant decrease of mGHR-fl in liver, no difference of mGHR-fl in muscle, and a significant increase of mGHR-fl in subcutaneous fat when compared with lit/+ mice. The mRNA of mGHR-282 was regulated in parallel with mGHR-fl in all tissues of all mice examined, whereas that of mGHR-280 was not changed in either GH-excess or GH-deficient states. In conclusion, two truncated isoforms of GHR mRNAs were detected in liver, skeletal muscle, and subcutaneous fat of mice. The ratio of GHR-tr to GHR-fl mRNA was tissue specific and not affected by chronic excess or deficiency of GH.

isoform; alternative splicing; dominant negative inhibition