HORMONES OF THE ADRENAL CORTEX

Abstract

Through repeated distribution between water and benzene, the whole extract of the adrenal cortex is divided into 2 fractions. Some of the active compounds remain in the benzene; some pass completely into the water phase. If the benzene is removed and replaced with isopropyl alc., compound A separates within 24-48 hrs. From the concentrated mother liquor of compound A, compound B will crystallize after the soln. has stood for some days. In the mother liquor after the removal of compound B there are present a number of crystalline steroid derivatives, chief among which is compound H. The compounds more soluble in water than in benzene are extracted from the aqueous soln. with chloroform, from which they can be crystallized. After compound E and related compounds have been separated there remains material easily soluble in the chloroform which has been described as the "amorphous fraction." If each of the fractions of the whole extract of the adrenal cortex is assayed by the method in which adrenalectomized dogs are maintained in a normal condition and the minimal amt. which is required is detd., then the "amorphous fraction," if properly prepared, can be shown to possess by far the greatest activity. This is because the "amorphous fraction" affects primarily renal function. The daily requirement per kg of body wt. to maintain the constituents of the blood within normal limits is less than 2[gamma]. If the influence on carbohydrate metabolism were used as a criterion, then the amorphous fraction would appear to be physiologically inert. Only those hormones which have an O2 attached to carbon 11 produce an effect on carbohydrate metabolism, but all of the 4 hormones which have this structure have much less of an effect on renal function than do those steroid derivatives related to desoxycorticosterone. One simple explanation for the high potency of some extracts when compared with others is the completeness with which the various hormones are extracted from the glandular material and are subsequently obtained in the aq. extract. Five topics which are of fundamental importance to the prep. of a potent extract from the gland are: pH and anti-oxidant effect, temp., the precipitation of lecithin, removal of last traces of lecithin, and removal of the hormones from the water. One of the most important details is associated with removal of the chloroform. A large part of the enhanced activity will be destroyed unless the hormones are transferred from the chloroform to water in a manner which will preserve the high potency.