期刊
ENDOCRINOLOGY
卷 146, 期 11, 页码 4898-4904出版社
ENDOCRINE SOC
DOI: 10.1210/en.2005-0587
关键词
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资金
- NIAAA NIH HHS [AA12865] Funding Source: Medline
- NIDDK NIH HHS [DK54880] Funding Source: Medline
- NINDS NIH HHS [NS46528, R01 NS046528, R01 NS045751, NS45751] Funding Source: Medline
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-tobrain influx transfer constants of I-125-labeled rat GH in mice (0.23 +/- 0.07 mu l/g(.)min) and rats (0.32 +/- 0.04 mu l/g(.)min) were comparable to those of some cytokines of similar size, with a half-time disappearance of I-125-GH of 3.8-7.6 min in blood. Intact I-125-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.
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