ADRENAL FUNCTION IN BREAST CANCER: BIOGENESIS OF ANDROGENS AND CORTISOL BY THE HUMAN ADRENAL GLAND IN VIVO

Abstract

SUMMARY A variety of 14C and 3H-labelled steroids have been perfused through the human adrenal gland in situ and their metabolic products isolated from adrenal venous blood. Progesterone, dehydroepiandrosterone and cortisol were isolated after infusion of [3H]pregnenolone; 17α-hydroxyprogesterone, dehydroepiandrosterone and cortisol after infusion of [3H]17α-hydroxypregnenolone and [14C]progesterone; androstenedione and cortisol after infusion of [3H]17α-hydroxyprogesterone and [14C]dehydroepiandrosterone; and 11β-hydroxyandrostenedione after infusion of [3H]androstenedione and [14C]cortisol. From a consideration of the incorporation of radioactivity into the metabolic products, the3H: 14C ratios and the tissue pool sizes it was concluded that the major biosynthetic pathway to cortisol in the human adrenal glands was: pregnenolone→ 17α-hydroxypregnenolone → cortisol. Progesterone was not an important intermediary. Androstenedione was mainly formed by way of 17α-hydroxypregnenolone → 17α-hydroxyprogesterone → androstenedione. 11β-Hydroxyandrostenedione was formed mainly from cortisol and only a minor amount came from the hydroxylation of androstenedione.