Molecular nature of interaction of steroids with biomembranes related to androgen biosynthesis

Abstract Pregnenolone and progesterone were found to be differentially concentrated in the membrane fractions from Leydig cell tumors and cryptorchid testes when equilibrium between membranes and the steroid containing buffer was achieved without metabolism. On the other hand, androstenedione was not significantly bound to any of the membranes. This concentrating system for pregnenolone and progesterone had high capacity and a low association constant. The amounts of pregnenolone bound to the mitochondria-rich fraction (MRF), smooth endoplasmic reticulum (SER) and rough endoplasmic reticulum (RER) were 4.8, 9.9 and 7.3 nmol/mg protein, respectively, when these fractions were incubated with 5 nmol of pregnenolone in 5 ml of the buffer. These differences, however, almost disappeared when the binding data were viewed in relation to the amount of membraneous phospholipid; that is, 0.3 for MRF, 0.29 for SER and 0.34 nmol/μg Pi of phospholipid for RER. The binding of pregnenolone to 3β-ol-dehydrogenase would be negligible, since tumor membranes which showed considerable variation in this enzymatic activity had a fairly constant capacity of the pregnenolone binding. Progesterone is bound to these fractions in a similar manner to pregnenolone. These results might suggest that the steroid-bio-membrane interaction occurs almost exclusively with phospholipids in membranes. The partition coefficients between the phospholipid in SER and the aqueous suspending medium were calculated to be 1.5 × 10 3 for pregnenolone, 2 × 10 2 for progesterone and 4.5 for androstenedione.