22 April 1967
Histocompatibility Tests-Johnson and Russell
Bach, F., and Hirschhorn, K. (1964). Science, 143, 813.
Bain, B., and Lowenstein, L. (1964).
Vas, M. R., and Lowenstein, L. (1964). Blood, 23, 108.
Brent, L., and Medawar, P. B. (1963).
Nature (Lond.), 204, 90.
Bridges, J. M., Nelson, S. D., and McGeown, M. G. (1964). Lancet, 1,
Chen, P. S. (1958).
Proc. Soc. exp. Biol. (N.Y.), 98, 546.
Gray, J. G., and Russell, P. S. (1963). Lancet, 2, 863.
(1965). In Histocompatibility Testing, edited by P. S. Russell
and H. J. Winn. Publication No. 1229, Nat. Acad. Sci., Washington,
Ibid., 145, 1315.
Brit. med. 7., 2, 269.
Harris, R., Clarke, C. A., Jones, A. L., Sheppard, P. M., Lehane, D.,
McCarthy, M., Lawler, S. D., and Shatwell, H. S. (1966).
med. 7., 1, 509.
Hirschhorn, K. (1965).
In Histocompatibility Testing, edited by P. S.
Russell and H.
Washington, p. 177.
Huggins, C. E. (1964). Ann. Surg., 160, 643.
Johnson, G. J., and Russell, P. S. (1965). Nature (Lond.), 208, 343.
Moorhead, J. F., and Patel, A. R.(1964).
Russell, P. S. (1966).
In Histocompatibility Testing 1965, edited by HE
Balner, F. J. Cleton, and J. G. Eernissc, p. 233. Copenhagen.
Streilein, J. W. (1966).
Ibid., p. 241.
J. Winn, Publication No. 1229, Nat. Acad.
Brit. med. 7., 2, 1111.
Conversion of Cortisone to Cortisol and Prednisone to Prednisolone
J. S. JENKINS,* M.D., M.R.C.P.; P. A. SAMPSON,t M.B., CH.B.
Brit. med. J., 1967, 2, 205-207
Though cortisone has been widely used since Hench et al.
arthritis, there is now considerable evidence that cortisone and
other steroids which possess the 1 1-oxo group instead of a
1l1l-hydroxyl are themselves biologically inactive.
application of cortisone to the skin is ineffective in the treat-
ment of skin diseases responsive to cortisol (Robinson and
Robinson, 1956), and when cortisone is injected locally into
inflamed joints its anti-inflammatory action is slight compared
with that of cortisol (Hollander et al., 1951).
11/3-hydroxydehydrogenase which renders the 11-oxo steroids
cortisone and its synthetic analogue prednisone biologically
active when they are administered systemically.
reaction appears to take place mainly in the liver (Jenkins,
1966). Several investigators have made clinical comparisons
of the therapeutic effects of cortisone and cortisol and of
prednisone and prednisolone, but there is less information about
the actual amounts of 11,8-hydroxysteroids which are formed
from the 11-oxo compounds. Peterson et al. (1957b) described
the conversion of cortisone to cortisol in one patient, but
the results were complicated by the prior administration of
9a-fluoroprednisolone to the patient.
studied the reduction of prednisone, again in only one patient,
but no comparison was made with the levels of prednisolone in
the plasma after prednisolone itself. The present paper describes
the extent to which oral cortisone and prednisone are con-
verted to cortisol and prednisolone in a series of normal subjects,
and also in patients suffering from liver disease.
its value in the treatment of rheumatoid
It is the reduc-
1 1/-hydroxyl by the enzyme
In man this
Bush and Mahesh (1964)
Procedure and Methods
Nine normal subjects, three patients with Addison's disease,
and four patients suffering from disease of the liver, were given
single oral doses of cortisone or prednisone as crushed tablets
in amounts ranging from 25 to 200 mg.
sions a similar dose of cortisol or prednisolone was given to the
At hourly intervals after the administration of
cortisone and cortisol the levels of cortisol in the plasma were
Similarly, the levels of prednisolone in the plasma
were measured after giving prednisone and prednisolone. Corti-
sone was administered mostly as the acetate, since this is the
usual form available for therapeutic use, but in some instances
the free alcohol was also given for comparison.
prednisone, and prednisolone were given as the free alcohol.
On subsequent occa-
After their oral administration the absorption of each of the
pair of steroids was compared by measuring the total 24-hour
excretion of 17-oxogenic steroids in the urine.
Cortisol in Plasma.-A fluorimetric technique (Rudd et al.,
1963) was used, by means of which cortisol can be measured
without interference from cortisone or other metabolites.
some cases plasma cortisol, tetrahydrocortisol, cortisone, and
tetrahydrocortisone were estimated
chromatographic technique similar to that described for the
estimation of plasma prednisolone, the appropriate standard
steroids being used.
plasma was extracted with 25 ml. of methylene chloride, and
the extract was washed first with 2 ml. of 0.1 normal sodium
hydroxide, followed by 0.1 normal acetic acid and finally with
The extract was evaporated to dryness, redissolved in
a small volume of a mixture of methanol and methylene
chloride, and applied to Whatman No. 1 chromatography paper.
Chromatograms were run for four hours in the benzene-
methanol-water (100:50:50) system of Bush (1952).
prednisolone area was located by ultraviolet light and eluted
with methanol from the chromatogram.
to dryness, redissolved in 0.5 ml. of methylene chloride, and
the steroid estimated, the phenylhydrazinesulphuric acid reagent
of Porter and Silber (1950) being used according to the tech-
nique of Peterson et al. (1957a).
solone were taken through the whole procedure.
17-Oxogenic steroids in the urine were estimated by the
method of Appleby et al. (1955).
specifically by a paper
The eluate was taken
Standard amounts of predni-
* Consultant Physician, St. George's Hospital, London S.W.1.
t Research Assistant, St. George's Hospital, London S.W.l.
Conversion of Cortisone to Cortisol
The mean levels of cortisol in the plasma after the oral ad-
ministration of 100 or 200 mg. of cortisone and cortisol to
normal subjects and 25 mg. of these steroids to patients with
Addison's disease are shown in Fig. 1.
ence was seen in the levels obtained with cortisone acetate and
the free alcohol when both were given to some of the subjects
on different occasions, and they have therefore not been recorded
The peak level after cortisone was normally at two
hours, but in all cases was lower than the peak after cortisol
This difference became disproportionately greater as the dosage
increased up to 200 mg., when plasma cortisol after cortisone
was only a third to half the level after cortisol.
unconjugated steroids present in the plasma of a normal subject
two hours after 200 mg. of cortisone and cortisol were examined
chromatographically, and are shown in Table I.
No significant differ-