C-19 oxygenated and nor metabolites of adrenal androgens and mineralocorticoids have received much attention in recent years. Although some studies on the central effects of these compounds have been carried out, they have focused on agents which are transported from the periphery. Recent results in our laboratory have established that 19-hydroxy and 19-oxo androstenedione are formed in situ in significant quantities in specific regions in the brain. We propose to identify whether steroids known to undergo C-19 oxidation in peripheral tissues are metabolized to similar product in CNS sites. More specifically, the metabolism of 11 beta-deoxycorticosterone (DOC) and 18-hydroxy- 11 beta- deoxycorticosterone (18-OH-DOC) to 19-oxygenated and 19-nor products will be examined by double isotope procedure using (C3H3)- and (14CH3)-DOC or 18-OH-DOC, synthesized with the label on the C-19 methyl group. New England Nuclear has agreed to synthesize sufficient amounts of radioactive compound for these studies using the procedures and precursors compounds provided by us. It has been proposed that the C-19 oxygenated and nor steroids act via a peripheral mechanism to influence blood pressure and therefore may be implicated in the establishment of hypertension. Studies in our laboratory have demonstrated that 19-hydroxy and 19-oxo androstenedione levels are greater in the CNS of SHR rats when compared to age matched WKY animals. We propose to examine whether the concentration of other C-19 steroid metabolites is different in these two strains of rats, and if the changes occur before or after the elevation of blood pressure in the SHR rats.
