Differential effects of insufflated, subcutaneous, and intravenous growth hormone on bone growth, cognitive function, and NMDA receptor subunit expression.
The objective of this study was to characterize the effect of inhalable growth hormone (GH) delivered by an insufflator to the lungs of hypophysectomized Sprague Dawley rats. In the first cohort, the safety and efficacy of the insufflated GH were evaluated. Three experimental groups (n = 7 per group) were treated with GH for 15 d: One group received sc injection of GH daily at 200 microg/kg (SC200). Two other groups received GH by insufflation daily: 200 microg/kg (INS 200) and 600 microg/kg (INS 600). In the second set of experiments, GH was administered in three routes [SC200, INS200, intravenous (IV200)] (n=10) for 5 d, and escape latency and N-methyl D-aspartate (NMDA) receptor expression were evaluated. In the first cohort, INS200 showed similar bioactivity as SC200 in growth promotion, tibial growth, as well as escape latency on the 12th day of treatment. Insufflated GH was well tolerated without significant inflammatory responses. In the second cohort, expression of the NMDA receptor 1 and 2B in hippocampus measured after 3 or 6 d of daily treatments were significantly higher in INS200 as compared to IV200, consistent with the improvement of the escape latency. In summary, the inhalable form of GH delivered by intratracheal insufflation was safe, and its bioactivity was comparable to sc injection both in promotion of growth and acquisition of learning ability. If applied properly to human, inhalable GH would be effective for growth promotion and possibly for several disorders caused by underexpression of NMDA receptors.
Park
Sung Won
SW
Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-dong, Gangnam-gu, Seoul 135-710, Korea.
Shin
Sooyoung
S
Kim
Chi Hwa
CH
Ko
Ah-ra
AR
Kwak
Min Jung
MJ
Nam
Mi Hyun
MH
Park
So Young
SY
Kim
Su Jin
SJ
Sohn
Young Bae
YB
Galinsky
Raymond E
RE
Kim
Hojoong
H
Yeo
Yoon
Y
Jin
Dong-Kyu
DK
D000818:Animals; D019540:Area Under Curve; D001846:Bone Development / Q000187:drug effects*; D003071:Cognition / Q000187:drug effects* / Q000502:physiology; D004924:Escape Reaction / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects; D013006:Growth Hormone / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007016:Hypophysectomy; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects; D008854:Microscopy, Electron; D011208:Powders / Q000737:chemistry / Q000302:isolation & purification; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
C409466:NR1 NMDA receptor; C120997:NR2A NMDA receptor; C121001:NR2B NMDA receptor; D011208:Powders; D016194:Receptors, N-Methyl-D-Aspartate; D013006:Growth Hormone