Abstrakt: |
A post-menopausal woman was found to excrete elevated amounts of urinary oestrogens. An adrenal carcinoma was removed and slices incubated in phosphate buffer, pH 7.4 with [14C] sodium acetate in combination with either [7α-3H] cholesterol, [7α-3H]dehydroepiandrosterone or [7α-3H]androstenedione. Radiochemically homogeneous tritium labelled oestrone, 17β-oestradiol and oestriol were isolated in each of the three experiments. Carbon-14 activity was incorporated into oestrone in each of the three experiments and into oestriol in one case only. No carbon-14 activity was associated with 17β-oestradiol isolated from any of the three incubations. Oestrone was found to be the predominant oestrogen synthesized in all experiments.When [14C]sodium acetate and [7α-3H]cholesterol (3H/14C ratio = 0.61) were used as substrates, the following compounds were isolated in a radiochemically homogeneous form (the isotopic ratio in each being shown in parenthesis): cholesterol (13.0), cholesterol sulphate (1.6), pregnenolone (1.0), pregnenolone sulphate (0.2), dehydroepiandrosterone (3.2), dehydroepiandrosterone sulphate (1.2), Δ5-androstenediol (3.1), Δ5-androstenediol sulphate (isolated as the unconjugated compound following solvolysis of the "disulphate" fraction (0.6), testosterone (1.1), testosterone sulphate (0.6), and oestrone (1.3).It is concluded that the adrenocortical carcinoma studied was capable of synthesizing oestrone, oestriol and cholesterol sulphate de novofrom acetate, and that the steroidogenic processes led to the predominant formation of Δ5-steroid sulphates. Furthermore, a comparison of the isotopic ratios in the various compounds isolated suggests that a number of unusual transformations may have occurred during steroidogenesis by the tumour cells in vitro. |