THE RELATIONSHIP BETWEEN STEROID PRODUCTION FROM ENDOGENOUS PRECURSORS AND FROM ADDED RADIOACTIVE PRECURSORS BY RAT ADRENAL TISSUE IN VITRO. THE EFFECT OF CORTICOTROPHIN

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Abstract
A method is described for the simultaneous measurement of mass and isotope content of five corticosteroids elaborated during incubations of rat adrenal tissue with added radioactive precursors. The compounds investigated were deoxycorticosterone, corticosterone, 18-hydroxydeoxycorticosterone, 18-hydroxycorticosterone, and aldosterone. Striking differences were observed between the incorporation of radioactive precursors and the tissues' endogenous precursors into these products. Steroid production from endogenous precursors and from radioactive precursors both showed wide variation, but there was no correlation between the two parameters. Furthermore, pituitary corticotrophin (ACTH) suppression, by prior in vivo administration of cortisol, specifically depressed the mass of subsequently formed corticosterone, while the incorporation of isotope into all the products was unaffected. Addition of ACTH (Synacthen®, Ciba) to the incubation medium partly restored the control condition. Experiments using adrenal capsule tissue and inner zone tissue alone showed that the production of deoxycorticosterone occurred throughout the cortex. The findings were interpreted as indicating that in rat adrenal in vitro incubations, exogenous and endogenous precursors by no means form a homogeneous pool. It is possible that conversion of radioactive precursors is governed only by the degree of penetration of the endogenous pool, whereas conversion of endogenous precursors may be affected by changes in hydroxylase activities, including those involved in the biosynthetic pathway after the point of pregnenolone formation.

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