Differential Effects of Insufflated, Subcutaneous, and Intravenous Growth Hormone on Bone Growth, Cognitive Function, and NMDA Receptor Subunit Expression

摘要

Theobjectiveofthisstudywastocharacterizetheeffectofinhalablegrowthhormone(GH)deliveredbyaninsufflatortothelungsofhypophysectomizedSpragueDawleyrats.Inthefirstcohort,thesafetyandefficacyoftheinsufflatedGHwereevaluated.Threeexperimental groups (n ? 7 per group) were treated with GH for 15 d: One group received sc injection of GH daily at 200 ? g/kg(SC200).TwoothergroupsreceivedtwodosesofGHbyinsufflationdaily:200 ? g/kg(INS200)and600 ? g/kg(INS600).Inthesecondset of experiments, GH was administered in three routes [SC200, INS200, intravenous (IV200)] (n ? 10) for 5 d, and escape latencyand N-methyl D-aspartate (NMDA) receptor expression were evaluated. In the first cohort, INS200 showed similar bioactivity asSC200ingrowthpromotion,tibialgrowth,aswellasescapelatencyonthe12thdayoftreatment.InsufflatedGHwaswelltoleratedwithout significant inflammatory responses. In the second cohort, expression of the NMDA receptor 1 and 2B in hippocampusmeasured after 3 or 6 d of daily treatments were significantly higher in INS200 as compared to IV200, consistent with theimprovement of the escape latency. In summary, the inhalable form of GH delivered by intratracheal insufflation was safe, andits bioactivity was comparable to sc injection both in promotion of growth and acquisition of learning ability. If applied properlyto human, inhalable GH would be effective for growth promotion and possibly for several disorders caused by underexpressionof NMDA receptors.