An in vitro study of mineralocorticoid binding proteins from rat kidney

Palem-Vliers, M; Genard, P.; Matagne, Daniel; Reuter, A.

doi:10.1016/0014-5793(74)80280-2

Cited by 4 publications

(1 citation statement)

References 11 publications

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“…This is in sharp contrast to hippocampal and lung studies, in which levels of MR decline nearer to term, whereas GR levels rise (18,32,38). The unique developmental profile of GR and MR in brain microvessels is important, because cortisol is known to act via both the GR and MR pathways (39,40). In this regard, the increased MR appears to play a key role in the mechanism of GC-induced up-regulation of brain microvessel P-gp.…”

Section: Discussionmentioning

confidence: 58%

Corticosteroid Regulation of P-Glycoprotein in the Developing Blood-Brain Barrier

2011

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The early fetal brain is susceptible to teratogens in the maternal circulation, because brain microvessel expression of drug efflux transporter, P-glycoprotein (P-gp), is very low. However, there is a dramatic up-regulation of brain microvessel P-gp in late gestation. This study investigated the role of cortisol and dexamethasone in this up-regulation of fetal brain microvessel P-gp expression. Primary brain endothelial cell (BEC) cultures derived from gestational d (GD)40, GD50, GD65 (term, ∼68 d) and postnatal d 14 male guinea pigs were treated with varying doses (10(-8) to 10(-5) m) of cortisol, dexamethasone, and aldosterone. After treatment, P-gp function was assessed using calcein-acetoxymethyl ester (P-gp substrate; 1 μm for 1 h) and measuring BEC accumulation of calcein. Corticosteroid treatment of BECs derived from postnatal d 14 resulted in increased P-gp activity. BECs derived from GD65 (near term) responded similarly, but these cells were extremely sensitive to the effects of mineralocorticoid receptor agonists (cortisol and aldosterone). BECs derived from GD50 displayed dose-dependent increases in P-gp function with dexamethasone (P < 0.05) and a trend towards increased function with cortisol. Cells derived from GD40 were unresponsive to all treatments. In conclusion, P-gp function in BECs is more responsive to glucocorticoids (GCs) in late gestation. Therefore, the late gestational surge in fetal plasma GCs, which parallels the increase in brain microvessel P-gp expression, may contribute to this P-gp up-regulation. Further, synthetic GCs (administered to pregnant women at risk of preterm delivery) may increase the protective capacity of the developing fetal blood-brain barrier, depending on the timing of GC exposure.

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