In vitro 6 beta-hydroxylation of progesterone in human renal tissue

Increased levels of 6 beta-hydroxylated steroids have been found in the urine of several species under different physiological and pathophysiological conditions. Until now, liver, adrenal glands and placenta have been identified as organs which contain 6 beta-hydroxylase activity. However, it has not yet been established whether 6 beta-hydroxylation occurs in mammalian kidney. In this study we have performed in vitro studies with preparations from rat and human kidney cortex and have obtained evidence for the presence of a small but significant renal 6 beta-hydroxylation activity. Two points deserve to be mentioned: 1) A species difference is documented by the presence of the enzyme in human, but not in rat kidney; 2) Substrate specificity is evident. Progesterone, but not corticosterone, was transformed to the 6 beta-hydroxylated metabolite in human tissue. The biological significance of the 6 beta-hydroxylation of endogenous, as well as exogenous steroids could be that 6 beta-hydroxylation opens an alternate route of progesterone metabolism in parallel to other conversion and/or degradation pathways. Furthermore, since other 6 beta-hydroxylated steroids have been reported to exert biological effects, this may also be the case with 6 beta-hydroxy progesterone.