19-nordeoxycorticosterone and 19-oxo-deoxycorticosterone

19-Nordeoxycorticosterone (19-nor-DOC) is a mineralocorticoid with several unresolved physiologic questions. First, is 19-nor-DOC synthesized in the kidney from a circulating adrenocortical precursor (19-oicdeoxycorticosterone [19-oic-DOC] or 19-oxodeoxycorticosterone [19-oxo-DOC])? Second, does 19-nor-DOC, synthesized in the kidney, have mineralocorticoid activity or is it excreted in the urine without biologic activity? To answer this question, we administered two of the putative 19-nor-DOC precursors (19-oxo-DOC and 19-oic-DOC) to adrenalectomized rats and measured the formation of 19-nor-DOC and bioactivity as the urinary Na+ to K+ ratio. Each of the 10-microgram steroid treatments produced an elevation of urinary-free 19-nor-DOC (0 to 2 hours), whereas at the 1-micrograms dose only 19-oic-DOCA produced an increased UF 19-nor-DOC. None of the treatments led to an increase of conjugated 19-nor-DOC except 10 microgram 19-oic-DOCA. Increased mineralocorticoid activity (decreased urinary Na+ to K+ ratio) was produced by aldosterone, 1 and 10 micrograms 19-nor-DOC, and 10 micrograms 19-oic-DOCA over the same time period. An anti-mineralocorticoid effect (increased urinary Na+ to K+ ratio) was produced by 1 microgram 19-oxo-DOC. Urinary-free 19-nor-DOC, but not conjugated 19-nor-DOC, correlated with the urinary mineralocorticoid effect (decreased Na+ to K+ ratio). These data support the contention that 19-oic-DOC is the circulating 19-nor-DOC precursor and that, at least at the higher dose, it has a mineralocorticoid action on the kidney.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adrenal Glands; Animals; Desoxycorticosterone; Male; Mineralocorticoids; Potassium; Rats; Rats, Inbred Strains; Sodium

19-Oxo-11-deoxycorticosterone was incubated with a cytochrome P-450(11)beta-reconstituted system, and the metabolites were analyzed by high performance liquid chromatography(HPLC). The main product found after chromatography was collected and treated with diazomethane. HPLC and 1H-NMR analysis of the methylated derivative indicated that it was 19-oic-11-deoxycorticosterone methyl ester. When 19-oic-11-deoxycorticosterone was stored at -20 degrees C for 1 month, it was spontaneously converted to other steroids. Structural analysis of the main degradation product indicated that it was 19-nor-11-deoxycorticosterone. These results suggest that the conversion of 19-oxo-11-deoxycorticosterone to 19-oic-11-deoxycorticosterone occurs through the P-450(11)beta-catalyzed reaction, and that the 19-oic-11-deoxycorticosterone thus formed is nonenzymatically converted into 19-nor-11-deoxycorticosterone.

Topics: Adrenal Cortex; Animals; Cattle; Chromatography, High Pressure Liquid; Desoxycorticosterone; Magnetic Resonance Spectroscopy; Mitochondria; Steroid 11-beta-Hydroxylase; Steroid Hydroxylases