The exon 3-retaining and the exon 3-deleted forms of the growth hormone-binding protein (GHBP) in human serum are regulated differently

OBJECTIVE Recently, two isoforms of the growth hormone-binding protein (GHB P), which is identical with the extracellular domain of the growth hormone receptor (GHR), have been described. One isoform contains the exon 3 (E3(+) GHBP) and one excludes the exon 3 (E3(-)GHBP). The distribution of both iso forms in peripheral blood and their functional relevance is so far unknown. DESIGN and PATIENTS To study the molecular distribution of both species we have analysed sera of 141 subjects with average weight, overweight and obes ity by newly developed immunoassays. The relationship between the different molecular forms of GHBP and specific parameters of body composition as wel l as risk factors of metabolic disturbances, were then examined. RESULTS The extracellular domain of the exon 3-retaining and -deleted isofo rms of the GHR are released as E3(+)GHBP and E3(-)GHBP into the peripheral circulation. Furthermore, both molecular species do not show any correlatio n to each other (r = 0.67) and their relative proportion in blood is gender -dependent with a higher E3(-)GHBP proportion in females (P < 0.01). E3(+)G HBP appears to have a considerably stronger correlation to indicators (BMI, fat mass, waist circumference) and metabolic risk factors (fasting insulin , uric acid, triglycerides, apolipoprotein B, diastolic blood pressure) of adiposity than E3(-)GHBP, indicating differences in their functional signif icance. CONCLUSIONS The availability of assays for the determination of GHBP isofor ms may be very important for the study of the GH receptor and its soluble e xtracellular domain, GHBP.