STUDIES OF THE BLOOD-CEREBROSPINAL FLUID BARRIER TO CORTISOL IN THE DOG*

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Abstract
The resting concentration of cortisol in cerebrospinal fluid is less than 1 [mu]g/100 ml in the anesthetized dog. After intravenous injection of cortisol or cortisol-21-hemisuccinate, the steroid enters the CSF rapidly, appearing there within 5-30 minutes. In a single experiment prolonged infusion of cortisol-21-hemisuccinate resulted by the 4th hour in the attainment of a steady state ratio, CSF/plasma, of 0.2. This can be interpreted as reflecting an 80% binding of cortisol to plasma protein. After cortisol or cortisol-21-hemisuccinate injection, only free (unconjugated) steroid, not the glucuronides of cortisol metabolites, appears in CSF, although a conjugated metabolic product, tetrahydrocortisol glucuronide is found in high concentration in plasma and urine. These findings are in accord with those concerning most drugs and natural products, i.e., that nonpolar, water-insoluble substances enter CSF from blood more readily than do polar, water-soluble compounds. Another metabolic product of cortisol, tetrahydro-cortisone freely enters the CSF, but tetrahydrocortisone glucuronide does not. The more rapid entry into CSF of tetrahydrocortisone than of cortisol may be explained by the lesser degree of binding to plasma protein of the former steroid. In the dog, cortisol is metabolized to tetrahydrocortisol only, not to tetrahydrocortisol, allo-tetrahydro-cortisol and tetrahydrocortisone, as in man. ACTH administration for 11 days did not alter cortisol entry into CSF or plasma "half-time" of administered steroid.

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