Testosterone transport in brain: primary role of plasma protein-bound hormone

1985 ◽  
Vol 249 (5) ◽  
pp. E534-E542 ◽  
Author(s):  
W. M. Pardridge ◽  
E. M. Landaw

Physiologically based mathematical modeling is used to predict the steady-state concentration of intracellular free and bound testosterone in brain. On the basis of previous in vivo tracer kinetic studies of blood-to-brain and brain-to-blood transport of testosterone in the rat, values are assigned to various physiological parameters (hormone association and dissociation reactions with plasma and cytosolic binding proteins, capillary transit time, and membrane transport). The model does not adhere to the restrictions of the free hormone hypothesis and allows for the enhanced transport of hormone from the plasma protein-bound pool into the tissue extravascular space. This process is believed to occur via an endothelial inhibition of ligand binding to the plasma protein without the protein crossing the endothelial wall. The model predicts that the steady-state concentration of intracellular free hormone changes in parallel more closely to changes in the concentration of plasma protein-bound hormone as measured in vitro and not the free hormone as measured in vitro.

1961 ◽  
Vol 201 (6) ◽  
pp. 1149-1151 ◽  
Author(s):  
Bernard Becker

In vitro preparations of rabbit choroid plexus accumulated I131 to a concentration 20–30 times the media. The accumulation was temperature dependent and was blocked by metabolic inhibitors. It could also be saturated with iodide, and was inhibited by perchlorate, fluoroborate, and related anions. In vivo the low 4-hr steady state concentration (1.6% of plasma) of trace doses of I131 in the rabbit cerebrospinal fluid was increased (to 40% of plasma) by the systemic administration of iodide or perchlorate. The results resembled qualitatively those obtained in the vitreous and aqueous humors of the same animals and suggested an active transport of iodide out of the cerebrospinal fluid, much as postulated previously for ocular fluids.


1992 ◽  
Vol 263 (2) ◽  
pp. R348-R352 ◽  
Author(s):  
S. Aebi ◽  
B. H. Lauterburg

There is a growing interest in the therapeutic use of sulfhydryls. To assess the effect of glutathione (GSH) and cysteine on the cellular thiol status, thiols were administered intravenously to rats in doses ranging from 1.67 to 8.35 mmol/kg with and without pretreatment with 4 mmol/kg buthionine-[S,R]-sulfoximine (BSO), an inhibitor of GSH synthesis. One hour after administration of 1.67 mmol/kg GSH, the concentration of GSH rose from 5.2 +/- 1.0 to 8.4 +/- 0.9 mumol/g and from 2.5 +/- 0.5 to 3.7 +/- 0.7 mumol/g in liver and kidneys, respectively. After 8.35 mmol/kg, hepatic GSH did not increase further, but renal GSH rose to 6.7 +/- 1.8 mumol/g. Infusion of cysteine increased hepatic GSH to the same extent as intravenous GSH, but renal GSH did not increase after 1.67 mmol/kg and even significantly decreased to 0.6 +/- 0.2 mumol/g after 8.35 mmol/kg. In the presence of BSO, GSH resulted in a significant increase in renal but not hepatic GSH, suggesting that the kidneys take up intact GSH and indicating that the increment in hepatic GSH was due to de novo synthesis. The present data show that hepatic GSH can be markedly increased in vivo by increasing the supply of cysteine. Measurements of hepatic cysteine indicate that up to a concentration of approximately 0.5 mumol/g cysteine is a key determinant of hepatic GSH, such that the physiological steady-state concentration of GSH in the liver appears to be mainly determined by the availability of cysteine. At higher concentrations GSH does not increase further, possibly due to feedback inhibition of GSH synthesis or increased efflux.(ABSTRACT TRUNCATED AT 250 WORDS)


Author(s):  
Susana Puntarulo

SynopsisBoth respiration and generation by soybean embryonic axes showed a sharp increase upon germination, leading to a significant increase in the steady-state concentration of and H2O2 after 6 h of imbibition. An assay was developed to assess in vivo generation of reactive oxygen species, based upon DCFH-DA oxidation. Fluorescence of the external medium was dependent on reaction time and axes number and was inhibited by catalase.α-Tocopherol content declined significantly after 24 h of incubation, as compared to the content at the onset of germination. Incubation in the presence of redox cycling agent paraquat (4 mM) for 24 h increased α-tocopherol content to 1.9±0.2 nmol per axis from 1.0 ± 0.1 nmol per axis in the absence of paraquat. Supplementation of the incubation medium with 500 μM Fe-EDTA increased α-tocopherol content to 1.8±0.1 nmol/axis and DCFH-DA oxidation by two-fold.The data presented here showed that active metabolism at the onset of germination increased steady-state concentration of oxygen active species and suggest that cellular content of α-tocopherol is physiologically adjusted as a response to conditions of oxidative stress.


1988 ◽  
Vol 66 (7) ◽  
pp. 772-779
Author(s):  
Lawrence Kleiman ◽  
Erich Schmedt ◽  
Harvey Miller

In this report, we have compared the changes in the production of [Formula: see text] (initiator tRNAMet) and tRNAAsn, which occur during erythroid differentiation in the Friend erythroleukemia cell. The relative steady-state concentration of these two tRNAs (relative to the total tRNA population) was measured by aminoacylation. The results show that while the relative steady-state concentration of [Formula: see text] changes very little in the cytoplasmic tRNA population, the relative concentration of tRNAAsn decreases during the first two days of differentiation and then undergoes an increase. This difference in the behavior of these two tRNAs is also seen when their relative concentrations in newly synthesized tRNA is examined. When tRNA is labeled with tritiated uridine for 24 h in vivo prior to isolation, the hybridization of this labeled tRNA to filter-bound tRNA genes shows that the relative concentration of [Formula: see text] in newly synthesized tRNA changes very little, while the relative concentration of newly synthesized tRNAAsn again decreases through the first 2 days of differentiation, and then undergoes a smaller increase. Thus, the production of these two tRNAs appears to be independently regulated. Independent regulation of synthesis is also observed when examining the production of these two tRNAs in isolated nuclei. During erythroid differentiation, the relative synthesis of [Formula: see text] (relative to total nuclear RNA synthesis) remains constant, while the relative synthesis of tRNAAsn undergoes periodic increases and decreases in value.


1964 ◽  
Vol 42 (4) ◽  
pp. 753-763 ◽  
Author(s):  
A. Y.-M. Ung ◽  
R. A. Back

The photolysis of water vapor at 1849 Å has been investigated as a possible source of hydroxyl radicals for kinetic studies. At temperatures from 23 to 350 °C and pressures from 1.3 to 28 mm, H2 and H2O2 were the only detectable products. Experiments with added oxygen indicated that O2 may have been present as an intermediate at a very low steady-state concentration, although this is not certain. Possible mechanisms are discussed.At temperatures from 200 to 350 °C, carbon monoxide appeared to react quantitatively with the hydroxyl radicals produced in the photolysis of water by the reaction, [Formula: see text] Rates of this reaction relative to those of the reactions, [Formula: see text] and [Formula: see text] were estimated from the decrement in the yield of CO2 when H2 or D2 was added to the H2O–CO system, and the following Arrhenius parameters were obtained:[Formula: see text]At temperatures below 200 °C, hydroxyl radicals were not completely converted to CO2, as the yield of CO2 increased to a maximum, then decreased again, with increasing pressure of CO. The mechanism of this system is complex, but probably involves secondary reactions of HCO or COOH radicals.


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