Synthesis of steroids in pancreas: Evidence of cytochrome P-450scc activity

In pancreas, the activities of several sex steroid-transforming enzymes hav e been reported. Data have been obtained in perfused organs, total tissue h omogenates, and subcellular organelles. These data, concurrent with the des cription of the presence of ligand-regulated steroid receptors, as well as the sexually dimorphic behavior of some pancreatic tumors, are clear eviden ce in support of the participation of steroid hormones in the pancreatic fu nction. In this study, the steroidogenic ability of the pancreas was demons trated by two different methods: (a) in tissue homogenates, by the identifi cation of cytochrome P-450scc gene (CYP11A) transcripts after reverse trans cription-polymerase chain reaction amplification (RT-PCR); and (b) in isola ted mitochondria by the glutethimide-dependent inhibition of cholesterol-pr egnenolone biotransformation. The results obtained in a series of independe nt experiments showed that (a) the pancreatic tissue possessed transcriptio nal activity of the CYP11A gene, although to a lesser extent than the typic al steroidogenic tissues, and (b) isolated mitochondria obtained from the p ancreas were able consistently to synthesize pregnenolone; furthermore, the addition of the specific inhibitor aminoglutethimide (AMG) blocked its syn thesis. On the whole, these findings are interpreted as clear evidences of the activity of the cytochrome P-450scc enzymatic complex (P450scc), respon sible for the transformation of cholesterol into pregnenolone and considere d the first and limiting step in steroid biosynthesis.