TY - JOUR
T1 - Physiological and pharmacological regulation of 20-kDa growth hormone
AU - Leung, Kin Chuen
AU - Howe, Chris
AU - Gui, Lily Y.Y.
AU - Trout, Graham
AU - Veldhuis, Johannes D.
AU - Ho, Ken K.Y.
PY - 2002/10
Y1 - 2002/10
N2 - The 20-kDa growth hormone (GH) is generated from alternative splicing of the primary transcript of full-length 22-kDa GH. We have studied the regulation of 20-kDa GH over a range of pathophysiological conditions and in response to pharmacological stimulation using isoform-specific enzyme-linked immunosorbent assays (ELISAs). Mean 24-h levels of 20- and 22-kDa GH were higher in acromegaly and lower in GH deficiency than in normal subjects, with the 20-to-22-kDa ratio not different between the three groups. In normal subjects, 20-kDa GH was secreted in a pulsatile manner throughout the day, with peaks coinciding with those of 22-kDa GH. However, the half-life of 20-kDa GH (18.7 ± 0.8 min) was significantly longer than that of 22-kDa GH (14.7 ± 0.8 min; P < 0.02). Insulin-induced hypoglycemia, androgen, and oral estrogen caused a parallel and proportionate increase in both isoforms. Octreotide suppressed 20-kDa less rapidly than 22-kDa GH in blood. Administration of recombinant 22-kDa GH in normal subjects rapidly reduced the 20-kDa GH levels. In conclusion, 20-kDa GH is cosecreted with and circulates at a constant proportion of 22-kDa GH. The 20-kDa GH level is reduced by administration of exogenous 22-kDa GH, suggesting rapid negative feedback regulation on pituitary release.
AB - The 20-kDa growth hormone (GH) is generated from alternative splicing of the primary transcript of full-length 22-kDa GH. We have studied the regulation of 20-kDa GH over a range of pathophysiological conditions and in response to pharmacological stimulation using isoform-specific enzyme-linked immunosorbent assays (ELISAs). Mean 24-h levels of 20- and 22-kDa GH were higher in acromegaly and lower in GH deficiency than in normal subjects, with the 20-to-22-kDa ratio not different between the three groups. In normal subjects, 20-kDa GH was secreted in a pulsatile manner throughout the day, with peaks coinciding with those of 22-kDa GH. However, the half-life of 20-kDa GH (18.7 ± 0.8 min) was significantly longer than that of 22-kDa GH (14.7 ± 0.8 min; P < 0.02). Insulin-induced hypoglycemia, androgen, and oral estrogen caused a parallel and proportionate increase in both isoforms. Octreotide suppressed 20-kDa less rapidly than 22-kDa GH in blood. Administration of recombinant 22-kDa GH in normal subjects rapidly reduced the 20-kDa GH levels. In conclusion, 20-kDa GH is cosecreted with and circulates at a constant proportion of 22-kDa GH. The 20-kDa GH level is reduced by administration of exogenous 22-kDa GH, suggesting rapid negative feedback regulation on pituitary release.
KW - Androgen
KW - Deconvolution analysis
KW - Estrogen
KW - Insulin-induced hypoglycemia
UR - http://www.scopus.com/inward/record.url?scp=0036785638&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0036785638&partnerID=8YFLogxK
M3 - Article
C2 - 12217902
AN - SCOPUS:0036785638
SN - 0193-1849
VL - 283
SP - E836-E843
JO - American Journal of Physiology - Endocrinology and Metabolism
JF - American Journal of Physiology - Endocrinology and Metabolism
IS - 4 46-4
ER -