In-vivo and in-vitro evidence of a carrier-mediated efflux transport system for oestrone-3-sulphate across the blood-cerebrospinal fluid barrier

J Pharm Pharmacol. 2000 Mar;52(3):281-8. doi: 10.1211/0022357001773968.


The efflux transport of oestrone-3-sulphate, a steroid hormone sulphate, across the blood-cerebrospinal fluid barrier has been examined following its intracerebroventricular administration. [3H]Oestrone-3-sulphate was eliminated from cerebrospinal fluid (CSF) with an apparent efflux clearance of 205 microL min(-1) per rat. There was 25% of unmetabolized [3H]oestrone-3-sulphate in the plasma 5 min after intracerebroventricular administration, indicating that at least a part of [3H]oestrone-3-sulphate is transported from CSF to the circulating blood across the blood-CSF barrier. This efflux transport was inhibited by co-administration of excess oestrone-3-sulphate (25 mM 10 microL = 0.25 micromol) into rat cerebral ventricle. To characterize the oestrone-3-sulphate transport process, an in-vitro uptake experiment was performed using isolated rat choroid plexus. Oestrone-3-sulphate uptake by isolated rat choroid plexus was found to be a saturable process with a Michaelis-Menten constant (Km) of 18.1 +/- 6.3 microM, and a maximum uptake rate (Vmax) of 48.0 +/- 15.1 pmol min(-1) microL(-1) of tissue. The oestrone-3-sulphate transport process was temperature dependent and was inhibited by metabolic inhibitors such as 2,4-dinitrophenol and rotenone, suggesting an energy dependence. This uptake process was also inhibited by steroid hormone sulphates (1 mM dehydroepiandrosterone sulphate and 1 mM oestrone sulphate), bile acids (1 mM taurocholic acid and 1 mM cholic acid) and organic anions (1 mM sulphobromophthalein and 1 mM phenolsulphonphthalein), whereas 1 mM p-aminohippuric acid, 1 mM p-nitrophenol sulphate, 0.1 mM methotrexate and the cardiac glycoside, 2.5 microM digoxin, had little effect. In conclusion, these results provide evidence that oestrone-3-sulphate is transported from CSF to the circulating blood across the blood-CSF barrier via a carrier-mediated efflux transport system.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2,4-Dinitrophenol / pharmacology
  • Animals
  • Bile Acids and Salts / pharmacology
  • Biological Transport / drug effects
  • Blood-Brain Barrier / physiology
  • Carbon Radioisotopes
  • Cardiac Glycosides / pharmacology
  • Carrier Proteins / physiology*
  • Cerebrospinal Fluid / metabolism
  • Choroid Plexus / metabolism*
  • Chromatography, High Pressure Liquid
  • Dehydroepiandrosterone / pharmacology
  • Dose-Response Relationship, Drug
  • Estrone / analogs & derivatives*
  • Estrone / blood
  • Estrone / cerebrospinal fluid
  • Estrone / pharmacokinetics
  • In Vitro Techniques
  • Injections, Intraventricular
  • Insulin / pharmacokinetics
  • Male
  • Phenolsulfonphthalein / pharmacology
  • Rats
  • Rats, Wistar
  • Rotenone / pharmacology
  • Sulfobromophthalein / pharmacology
  • Temperature
  • Time Factors
  • Tritium
  • Uncoupling Agents / pharmacology


  • Bile Acids and Salts
  • Carbon Radioisotopes
  • Cardiac Glycosides
  • Carrier Proteins
  • Insulin
  • Uncoupling Agents
  • Rotenone
  • Sulfobromophthalein
  • Tritium
  • Estrone
  • Dehydroepiandrosterone
  • Phenolsulfonphthalein
  • 2,4-Dinitrophenol
  • estrone sulfate