Relative abundance of growth hormone receptor isoforms in rhesus monkey tissues and human transformed lymphocytes.
The growth hormone receptor (GHR) is expressed as one active, full-sequence isoform and one truncated, inactive one that lacks the intracellular signaling domain. The aim of this study was to investigate the variation in the tissue expression of the full and truncated mRNA and protein. Epstein-Barr virus-transformed human B lymphocyte lines were established from 9 normal individuals with a height standard deviation score (SDS) of - 0.1 +/- 1.1 (mean +/- SD). Tissues were also collected from 3 Rhesus monkeys, whose GHR has 94.1 % homology with the human molecule. mRNA quantitation was determined by Real Time Quantitative PCR. Growth hormone receptor expression in transformed lymphocytes was also studied by fluorescence-activated cell sorter analysis. Both isoforms were expressed in transformed lymphocytes, but individual variation in the relative mRNA expression was small (truncated isoform percentage of total receptor mRNA: 17.1 +/- 4.4, mean +/- SD). There was no correlation between donors' height SDS and the expression of either isoform or the ratio between them. Protein expression by FACS analysis showed wider variation among the subjects; however, the relative ratio was similar in all the subjects. In monkey tissues, the truncated receptor showed a tissue-specific distribution. In conclusion, the expression of both isoforms in transformed lymphocytes from normal subjects shows small differences at the RNA or protein levels, and does not correlate with height SDS. Growth hormone splice isoforms show tissue specificity, suggesting local regulation of splicing. Tissues with relatively high expression of the truncated isoform are likely to be more resistant to the effects of GH due to the dominant negative effect of this isoform. In addition, the differential tissue expression might influence the levels of growth hormone binding protein in the immediate milieu of each tissue.
Vottero
A
A
PREB/NICHD/NIH, Bethesda, MD, USA. vottero@nemmo.unipr.it
Kimchi-Sarfaty
C
C
Kratzsch
J
J
Miller
G
G
Lafferty
A
A
Chrousos
G P
GP
Hochberg
Z
Z
D000328:Adult; D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism; D017931:DNA Primers; D005260:Female; D005434:Flow Cytometry; D004854:Herpesvirus 4, Human / Q000276:immunology; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D007536:Isomerism; D008213:Lymphocyte Activation / Q000502:physiology*; D008214:Lymphocytes / Q000378:metabolism*; D008253:Macaca mulatta; D008297:Male; D012333:RNA, Messenger / Q000096:biosynthesis; D011986:Receptors, Somatotropin / Q000096:biosynthesis / Q000378:metabolism*
D017931:DNA Primers; D012333:RNA, Messenger; D011986:Receptors, Somatotropin