Regulation of full-length and truncated growth hormone (GH) receptor by GH in tissues of lit/lit or bovine GH transgenic mice.
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.
Iida
Keiji
K
Department of Internal Medicine, University of Virginia, Charlottesville, Virginia 22908, USA. iidak2@aol.com
del Rincon
Juan P
JP
Kim
Dong-Sun
DS
Itoh
Emina
E
Coschigano
Karen T
KT
Kopchick
John J
JJ
Thorner
Michael O
MO
D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D001483:Base Sequence; D002417:Cattle; D004392:Dwarfism / Q000235:genetics / Q000378:metabolism*; D013006:Growth Hormone / Q000235:genetics / Q000502:physiology*; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic / Q000235:genetics; D018482:Muscle, Skeletal / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism; D011986:Receptors, Somatotropin / Q000235:genetics / Q000378:metabolism*; D040521:Subcutaneous Tissue / Q000378:metabolism
D010446:Peptide Fragments; D011986:Receptors, Somatotropin; D013006:Growth Hormone