Corticosteroid biosynthesis from pregnenolone and progesterone by human adrenal tissue in vitro. A kinetic study

Using a kinetic approach, a study has been made of the pathways of corticosteroid biosynthesis from 3H -pregnenolone and 14C — progesterone in human adrenal tissue. In the adult, the dissimilarity between the 3H — and 14C -product yield-time curves suggested that the two precursors were handled quite differently. In particular it appeared that 17-hydroxypregnenolone, which bore only the 3H label, acted as an intermediate in the formation of 3H -cortisol from 3H -pregnenolone whereas only slight amounts of 3H -progesterone were formed. From 14C -progesterone, the formation of 14C -corticosterone and 14C -cortisol proceeded via the ‘classical’ pathways. In the foetus, the lack of 17-hydroxypregnenolone dehydrogenase seems to account for the relatively minute yields of 3H -corticosteroids from 3H -pregnenolone. The pattern of 14C -progesterone metabolism in the foetus was the same as in the adult. These results are in agreement with the general conclusions reached by other authors in non-kinetic studies with human adrenal tissue, but are in striking contrast with the results obtained with adrenal tissue from other species.