PATHWAYS FOR BIOSYNTHESIS OF CORTICOSTEROIDS FROM PREGNENOLONE BY ADRENAL TISSUE OF FROG RANA RUGULOSA

The formation of corticosteroids from pairs of differently labeled precursors was studied using adrenal tissue from the frog, Rana rugulosa. The precursors chosen were [16-3H]-pregnenolone and [4-14C]-progesterone; [4-14C]-progesterone and [1,2-3H]-deoxycorticosterone; [1,2-3H]-deoxycorticosterone and [4-14C]-corticosterone. Products were isolated after different periods of time, and product yield time curves were constructed. From pregnenolone, one compound was formed which was not produced from the other precursors. Its identity is unknown, but it does not seem likely that this played a part as an intermediate. Otherwise, all of the products isolated during the experiments were doubly labeled, and produced in a similar manner from both precursors. Furthermore, the maximal incorporation of radioactive label into the different products showed a clearly defined sequence. From these results it appears that in the frog adrenal, the main pathway for the formation of corticosteroids from pregnenolone is: pregnenolone→progesterone→deoxycorticosterone {A figure is presented}. Other pathways, particularly those which envisage 11β-hydroxyprogesterone or 18-hydroxycorticosterone as intermediates, appear to be relatively unimportant. It is particularly noteworthy that progesterone and pregnenolone were equally good precursors of the corticosteroids. In this respect the adrenal of the frog resembles that of other submammalian tetrapods, but shows a marked contrast with those from certain mammalian species. © 1969.