IN-VITRO 6-BETA-HYDROXYLATION OF PROGESTERONE IN HUMAN RENAL TISSUE

Increased levels of 6 beta-hydroxylated steroids have been found in th e urine of several species under different physiological and pathophys iological conditions. Until now, liver, adrenal glands and placenta ha ve been identified as organs which contain GB-hydroxylase activity. Ho wever, it has not yet been established whether 6 beta-hydroxylation oc curs in mammalian kidney. In this study we have performed in vitro stu dies with preparations from rat and human kidney cortex and have obtai ned evidence for the presence of a small but significant renal 6 beta- hydroxylation activity. Two points deserve to be mentioned: 1) A speci es difference is documented by the presence of the enzyme in human, bu t not in rat kidney; 2) Substrate specificity is evident. Progesterone , but not corticosterone, was transformed to the 6 beta-hydroxylated m etabolite in human tissue. The biological significance of the 6 beta-h ydroxylation of endogenous, as well as exogenous steroids could be tha t 6 beta-hydroxylation opens an alternate route of progesterone metabo lism in parallel to other conversion and/or degradation pathways. Furt hermore, since other 6 beta-hydroxylated steroids have been reported t o exert biological effects, this may also be the case with 6 beta-hydr oxy progesterone.