KINETIC STUDIES ON THE ENZYMES CATALYSING THE CONVERSION OF 17α-HYDROXY-PROGESTERONE AND DEHYDROEPIANDROSTERONE TO ANDROSTENEDIONE IN THE HUMAN ADRENAL GLAND IN VITRO

Abstract

SUMMARY Factors controlling the synthesis of androstenedione in the human adrenal gland were investigated in a kinetic study of the enzymes catalysing the conversion of 17α-hydroxyprogesterone and dehydroepiandrosterone to the hormone. Both reactions are associated with the microsomal fraction of the adrenal cell. 17α-Hydroxyprogesterone is converted to androstenedione by a NADPH-dependent 17-desmolase whereas there is an obligatory requirement for NAD+ for the conversion of dehydroepiandrosterone to the hormone. None of the other cofactors investigated inhibited or enhanced the enzymic conversions. The side-chain cleavage of 17α-hydroxyprogesterone was competitively inhibited by the precursors of the substrate, pregnenolone, progesterone and 17α-hydroxypregnenolone. Other C19 or C18 compounds known to be synthesized by the human adrenal gland were found to be ineffective in modifying the enzyme action. The conversion of dehydroepiandrosterone to androstenedione was non-competitively inhibited by oestrone and oestradiol-17β. No C21 compounds were found to affect the reaction. 5α-Dihydrotestosterone (17β-hydroxy-5α-androstan-3-one) inhibited both enzymic conversions competitively but the inhibition constants observed were so high that it is unlikely that this finding has any relevance to the control of androstenedione synthesis in vitro.