Metabolism of Pregnenolone and Dehydroepiandrosterone by Homogenized Tissue From the Separated Zones and Whole Adrenal Glands From Newborn Anencephalic Infants

Abstract

SUMMARY The metabolism of [3H]pregnenolone and [3H]dehydroepiandrosterone ([3H]DHA) by tissue from the separated zones and whole adrenal glands from newborn anencephalic infants was investigated. Pregnenolone was metabolized by the whole gland homogenates mainly to pregnenolone sulphate and unconjugated 17α-hydroxypregnenolone and also to small amounts of DHA and dehydroepiandrosterone sulphate (DHAS). DHA was metabolized by the whole gland homogenates mainly to androstenedione and DHAS and small amounts of 11β-hydroxyandrostenedione. Adrenal gland tissue from a 42-week-old anencephalic infant containing three histologically distinct zones in the adult cortex in addition to residual foetal zone had sulphokinase, 17α-hydroxylase, 17–20 lyase and 3β-hydroxy-steroid dehydrogenase/Δ4,5 unsaturated isomerase activity in each of these zones. These enzymes were also present in the adrenal adult zone of another anencephalic infant. Omission of ATP from the incubation medium greatly reduced the conversion of DHA to DHAS in the homogenates and separated zones. These results are discussed in relation to oestrogen biosynthesis in anencephaly and to foetal 4-en-3-oxosteroid synthesis in utero.

Human Foetal Adrenal 4-Ene-3-Oxosteroid Synthesis: An Investigation of [4-14c]pregnenolone and [4-14c]-Dehydroepiandrosterone Metabolism Using New Techniques

“…The possibility that factors outside the tissue are responsible for the lack of 4-ene-3-oxosteroid formation from pregnenolone is to some extent militated against by the facts that: (1) both foetal adrenal and carcinoma tissue converted DHA to 4-ene-3-oxosteroids; (2) the same two tissues showed evidence of ability to convert pregnenolone (and DHA) to other 3/?-hydroxysteroids and to conjugates ; (3) carcinoma tissue converted pregnenolone to 4-ene-3-oxosteroids. If then, the tissue is responsible for the lack of conversion, the reasons for this may include : (a) the presence of an enzymic inhibitor, possibly progesterone as suggested by Villee (1967); (b) competition by other enzymes for the substrate, possibly by a sulphokinase as suggested by the results of Cooke, Shirley, Dobbie & Taylor (1971) who used tissue from anencephalic newborn infants; (c) deficiency or absence of requisite enzyme(s), as has often been assumed.…”