Key result
20K-hGH had 10-fold lower activity than 22K-hGH in cell proliferation but equal activity in gene promoter activation, indicating cellular activities do not necessarily correlate with binding affinity.
The cellular activities of 20K- and 22K-hGH do not necessarily correlate with their binding affinities for the rat growth hormone receptor.
May diverge from binding predictions in GH therapy; leaves open isoform-specific signaling mechanisms for further study.
Even though 20K human growth hormone (20K-hGH) has 3-10% binding affinity for the rat liver and adipose tissue microsomes as compared to 22K-hGH, it was also reported that 20K-hGH has the same potency as 22K-hGH in the hypophysectomized rat weight gain assay. In order to investigate the reason why such controversial data exist, we have studied 20K- and 22K-hGH using the rat GH receptor extracellular domain (rGHR-ECD) and full-length rGHR. When we examined the complex formation of rGHR-ECD with 20K- and 22K-hGH in gel filtration assay, 20K-hGH formed no complex while 22K-hGH formed a 1:1 complex. Next, rGHR cDNA was introduced into Ba/F3 cells and CHO-K1 cells, and stable transfectants (Ba/F3-rGHR and CHO-rGHR) were established. In the proliferation of Ba/F3-rGHR cells, 20K-hGH had 10-fold lower activity than 22K-hGH, which is consistent with their affinities for rGHR. But surprisingly, in the Spi2.1 gene promoter activation in CHO-rGHR cells, 20K- and 22K-hGH had the same activity, which was found not only in stable CHO-rGHR clones but also in CHO-K1 cells transiently expressing rGHR. In conclusion, these results indicate that cellular activities of 20K- and 22K-hGH do not necessarily correlate with their binding affinities for rGHR.
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Ikeda et al. (2000) studied this question. 20K-hGH vs. 22K-hGH was evaluated on Complex formation, cell proliferation, and gene promoter activation. 20K-hGH had 10-fold lower activity than 22K-hGH in cell proliferation but equal activity in gene promoter activation, indicating cellular activities do not necessarily correlate with binding affinity.
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