STUDIES ON THE ADRENAL CORTEX

Abstract

[long dash]I. The survival period of 38 untreated control suprarenalectomized cats was 4-15 days (av. 7.7 days). The survival period of 23 double suprarenalectomized cats treated with a crude lipid fraction of beef suprarenal cortex, obtained by alcoholic-benzene extraction, was 16-60 days (av. 27.8 days). The behavior of the extract-treated animals was normal up to the abrupt appearance of suprarenal insufficiency symptoms a few days before death. The primary object of the study was the conclusive demonstration of the presence of the cortical hormone in the crude lipid fraction. The cortical hormone is stable in ethyl alcohol for a period of at least 2 wks., and the crude lipid fraction when prepared in oil retains its potency for about 3 wks. when kept at 6[degree] C. The active lipid fraction is not epinephrine free. In so far as the authors are aware this is the first conclusive demonstration that the hormone of the suprarenal cortex which is essential for the maintenance of life can be extracted with lipid solvents. II. The effect of various fractions of the crude lipid extract of beef suprarenals was tested on 32 double-suprarenalectomized cats. The acetone-soluble fraction was highly active; all 5 cats tested as long as the extract was continued (30-50 days). It contains the cortical hormone but presents serious difficulties of administration (formation of lumps and sloughs at site of injection). The acetone-insoluble fraction did not prolong the life of the 3 suprarenalectomized cats on which it was used; it seems inactive. Of 5 cats on which the petroleum-ether-soluble fraction was tested, 2, which received the fraction following a single distribution between petroleum-ether and 70% alcohol, survived 22 and 19 days respectively; the 3 others, which received a fraction obtained after 4 distributions, survived 4.8 days, indicating that after 4 distributions the petroleum-ether fraction is inactive. Of 19 suprarenalectomized cats treated with the alcohol-soluble fraction obtained after distribution between petroleum-ether and 70% alcohol, all lived in good health throughout the arbitrarily selected 100-day treatment period and died with symptoms of suprarenal insufficiency on cessation of treatment, except 3 killed at the end of 50 days and 4 which died of pneumonia, generalized infections or fits. Hence this extract contains the "cortical hormone" or hormone of the suprarenal cortex. This aqueous extract is protein-free but not epinephrine free, containing an average of about 0.4% of the epinephrine present in fresh cortical substance. Potent extracts have been prepared from adrenal cortex stored in alcohol at room temp. for periods of 2-3 wks. No deterioration in activity was observed in active fractions stored in alcohol or benzene at 8[degree] C. from 4-6 wks. Active fractions can be safely stored in acetone for several days. The authors'' tests indicate that there is no loss of activity in aqueous extracts in 7-14 days when stored at 8[degree] C. without a preservative. III. For use on cats near death from suprarenal insufficiency a potent "cortical extract" practically free from epinephrine was required. A method is described for the preparation of extract containing about 1:2,000,000 suprarenalin and potent enough to restore suprarenalectomized cats repeatedly to normal.