Submitted on March 5, 2004
Accepted on May 25, 2004
Regulation of full-length and truncated growth hormone (GH) receptor by GH in tissues of lit/lit or bovine GH transgenic mice
Keiji Iida1*, Juan P. del Rincon1, Dong-Sun Kim1, Emina Itoh1, Karen T. Coschigano2, John J. Kopchick3, and Michael O. Thorner1
1 Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Virginia, Charlottesville, Virginia, USA
2 Edison Biotechnology Institute, Ohio University, Athens, Ohio, USA
3 Edison Biotechnology Institute, Ohio University, Athens, Ohio, USA; Department of Biomedical Sciences, College of Osteopathic Medicine, Ohio University, Athens, Ohio, USA
* To whom correspondence should be addressed. E-mail: iidak2{at}aol.com.
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 using 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 -280) were 0.5% and less than 0.1% 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 bGH
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 either in GH excess or deficient states. In conclusion, two truncated
isoforms of GHR mRNAs were detected in liver, skeletal muscle, and subcutaneous fat of mice.
The GHR-tr/GHR-fl mRNA ratio was tissue-specific and not affected by chronic excess or
deficiency of GH.
