INTERACTIONS BETWEEN GLUCOCORTICOIDS AND MINERALOCORTICOIDS IN THE REGULATION OF RENAL ELECTROLYTE TRANSPORT

The enzyme 11 beta-hydroxy steroid dehydrogenase (11 beta-OHSD) was de scribed and its location in various organs noted more than 30 years ag o (Mahesh and Ulrich, 1960; Jenkins, 1966). 11 beta-OHSD inactivates c irculating glucocorticoids by transforming the hydroxyl group at the 1 1-carbon to a keto group. This chemical reaction has taken on a greate r degree of physiologic and clinical significance in recent years. It has been suggested that 11 beta-OHSD, present in mineralocorticoid tar get tissues, can act as a ''guardian'' over the mineralocorticoid rece ptor by transforming circulating endogenous glucocorticoids to their r espective ''biologically inert'' ll-dehydro derivatives (Edwards et al ., 1988; Funder et al., 1988). These derivatives do not bind to minera locorticoid receptors (MR) while both their parent compounds and miner alocorticoids bind to cloned MR with equal affinity (Arriza et al., 19 87). 11 beta-OHSD has generated a growing sense of scientific exciteme nt since this enzyme may represent one of a family of metabolic pathwa ys or mechanisms which can regulate steroid induced renal reabsorption of sodium. Such ''protective'' enzymatic pathways, present in the kid ney and elsewhere, may not only control the access of glucocorticoids to MR, but control the access of glucocorticoids to glucocorticoid rec eptors (GR) (Teelucksingh et al., 1990; Mender, 1990) as well as acces s of mineralocorticoids to their own receptors. This review will focus on this concept of a family of protective enzymatic pathways and the possible physiological implications.