IN VITRO STUDIES ON ENZYMATIC CLEAVAGE OF STEROID ESTERS IN THE FEMALE ORGANISM

ABSTRACT The decreasing water-solubility of steroid esters concomitant with increasing chain length of monocarboxylic acids provides a prolonged therapeutic effect of the steroid. Whether a slow release of the steroid from an oily depot in the muscle or a secondary storage of the ester in the body fat ("deep compartment") are responsible for this prolonged action, is open to discussion. The aim of this study was to investigate the steroid ester cleaving enzyme activity of human subcutaneous fatty tissue. The following steroid esters were investigated: Testosterone acetate and oenanthate, metenolone acetate and oenanthate, norethisterone acetate and oenanthate, dehydroepiandrosterone acetate and oenanthate, fluocortolone acetate and caproate. In the 10 000 x g supernatant phase of the female subcutaneous fatty tissue the rate of enzymatic cleavage of the long-chain oenanthates was considerably greater than that of the corresponding short-chain steroid esters. The nature and position of the ester group in the steroid molecule exhibited a marked effect on the rate of enzymatic cleavage of steroid esters. The cleavage rate of long- and short-chain steroid esters in human myometrium and endometrium resembled that in the fatty tissue. On the other hand, the gastric mucosa, rectus musculature, placenta and vaginal mucosa split the short-chain steroid esters more rapidly than the long-chain esters. The marked differences in the relation of the cleavage rate of long- and short-chain steroid esters in the various tissues allow the assumption that long- and short-chain steroid esters are cleaved by different enzymes.