Physiological and pharmacological regulation of 20-kDa growth hormone.
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.
Leung
Kin-Chuen
KC
Pituitary Research Unit, Garvan Institute of Medical Research, St. Vincent's Hospital, Sydney, New South Wales 2010, Australia. kleung@garvan.org.au
Howe
Chris
C
Gui
Lily Y-Y
LY
Trout
Graham
G
Veldhuis
Johannes D
JD
Ho
Ken K Y
KK
D000172:Acromegaly / Q000188:drug therapy* / Q000378:metabolism*; D000293:Adolescent; D000328:Adult; D000368:Aged; D004967:Estrogens / Q000008:administration & dosage; D025461:Feedback, Physiological / Q000187:drug effects / Q000502:physiology; D005260:Female; D012739:Gonadal Steroid Hormones / Q000008:administration & dosage; D006728:Hormones / Q000008:administration & dosage; D019382:Human Growth Hormone / Q000008:administration & dosage* / Q000097:blood* / Q000172:deficiency; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage; D007018:Hypopituitarism / Q000188:drug therapy* / Q000378:metabolism*; D007328:Insulin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D015282:Octreotide / Q000008:administration & dosage; D013739:Testosterone / Q000008:administration & dosage
D004967:Estrogens; D012739:Gonadal Steroid Hormones; D006728:Hormones; D007004:Hypoglycemic Agents; D007328:Insulin; D019382:Human Growth Hormone; D013739:Testosterone; D015282:Octreotide