Permeation of growth hormone across the blood-brain barrier.
Exogenous GH can affect central nervous system function when given peripherally to animals and as a supplemental therapy to humans. This study tested whether GH crosses the blood-brain barrier (BBB) by a specific transport system and found that both mice and rats have small but significant uptake of GH into the brain without a species difference. Determined by multiple-time regression analysis, the blood-to-brain influx transfer constants of 125I-labeled rat GH in mice (0.23+/-0.07 microl/g.min) and rats (0.32+/-0.04 microl/g.min) were comparable to those of some cytokines of similar size, with a half-time disappearance of 125I-GH of 3.8-7.6 min in blood. Intact 125I-GH was present in both serum and brain homogenate 20 min after iv injection. At this time, about 26.8% of GH in brain entered the parenchyma, whereas 10% was entrapped in endothelial cells. Neither excess GH nor insulin showed acute modulation of the influx, indicating lack of a saturable transport system for GH at the BBB. Binding and cellular uptake studies in cultured cerebral microvessel endothelial cells (RBE4) further ruled out the presence of high-capacity adsorptive endocytosis. The brain influx of GH by simple diffusion adds definitive value to the long-disputed question of whether and how GH crosses the BBB. The central nervous system effects of peripheral GH can be attributed to permeation of the BBB despite the absence of a specific transport system.
Pan
Weihong
W
Pennington Biomedical Research Center, Louisiana State University System, 6400 Perkins Road, Baton Rouge, Louisiana 70808, USA. weihong.pan@pbrc.edu
Yu
Yongmei
Y
Cain
Courtney M
CM
Nyberg
Fred
F
Couraud
Pierre O
PO
Kastin
Abba J
AJ
D000818:Animals; D001808:Blood Vessels / Q000378:metabolism; D001812:Blood-Brain Barrier; D001921:Brain / Q000098:blood supply / Q000378:metabolism; D002199:Capillary Permeability; D002460:Cell Line; D042783:Endothelial Cells / Q000378:metabolism; D013006:Growth Hormone / Q000493:pharmacokinetics*; D019382:Human Growth Hormone / Q000493:pharmacokinetics; D006801:Humans; D007275:Injections, Intravenous; D007457:Iodine Radioisotopes; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D010477:Perfusion; D011107:Polylysine / Q000494:pharmacology; D011479:Protamines / Q000494:pharmacology; D051381:Rats; D011994:Recombinant Proteins / Q000493:pharmacokinetics
D007457:Iodine Radioisotopes; D011479:Protamines; D011994:Recombinant Proteins; D019382:Human Growth Hormone; D011107:Polylysine; D013006:Growth Hormone