title: Metabolism of dehydroepiandrosterone by the adrenal gland of the human foetus and newborn infant
Creators: name: Shirley, Ian M.
Publisher: name: University of Glasgow
Year: 1970

description: A microtechnique, which permits histological monitoring of tissue sections used for biochemical investigations, has been applied to the study of 3β-hydroxy-5-androsten-17-one (dehydroepiandrosterone, DHA) metabolism in the adrenal gland of the human foetus and newborn infant, Homogenates and chopped tissue preparations of adrenal glands from previable human foetuses incubated in the presence of exogenous ATP metabolized much more DHA to DHA sulphate (31 - 95%) than to androst-4-ene-3,17-dione (androstenedione) (0.2 - 2.8%), The results of experiments to examine the effects of variations of the length of the incubation period, of the tissue:steroid ratio and of the co-factor content of the incubation medium suggest that there exists, in the adrenal gland of the previable human foetus, a deficiency of the levels of 3β-hydroxysteroid dehydrogenase (EC 1.1.1.51) and/or steroid Δ4- Δ5 isomerase (EC 5.3.l) relative to those of DHA sulphokinase (EC 2.8.2.1), The sulphoconjugation of DHA was highly dependent on the presence of ATP in the incubation medium. Adult zone tissue from the adrenal gland of a previable foetus converted more DHA to androstenedione (0.27%) than did tissue from the foetal zone (0.15%). The latter zone formed much more DHA sulphate (27%) from DHA than the adult zone (7%). Neither zonal fraction, nor a whole gland preparation, metabolized DHA to 11Δ-hydroxyandrostenedione. The quantitative histological distribution of DHA sulphokinase and 3β-hydroxysteroid dehydrogenase-isomerase activities was investigated in the adrenal glands of 5 previable foetuses, DHA sulphokinase activity was restricted mainly to the foetal zone of the glands and, in the presence of ATP, 3β-hydroxysteroid dehydrogenase-isomerase activity was slightly greater in the adult than in the foetal zone. The distribution of these enzyme activities in the absence of exogenous ATP suggests that the foetal zone, while possessing higher levels of 3β-hydroxysteroid dehydrogenase-isomerase, displays less in vitro activity of this enzyme system due to competition for substrate with the active DJIA sulphokinase system. Evidence was obtained for the existence, in the region of the adult/foetal zone junction, of cells which possess enhanced activities of the DHA sulphokinase and 3β-hydroxysteroid dehydrogenase-isomerase systems. Adult zone tissue from the adrenal gland of a newborn hydrocephalic infant converted more DHA to androstenedione (33%) than did foetal zone tissue (3.4%) and less DHA to DHA sulphate than the foetal zone (adult zone: 4.6%; foetal zone: 21%), 3β-Hydroxysteroid dehydrogenase activity in both zones was greater than in the corresponding zonal fractions from the adrenal gland of the previable foetus. Adult zone tissue from the adrenal gland of a newborn post-mature anencephalic infant converted 32 - 69% of the incubated DHA to androstenedione. The formations of DHA sulphate (maximum 69%) were similar to those obtained in the foetal zone of the adrenal glands of previable foetuses. Adult zone