19-nordeoxycorticosterone and 19-norcorticosterone

Incubation of rat adrenal homogenates with tritiated and unlabeled 19-nor-deoxycorticosterone yielded, in addition to unconverted starting substrate, two major radioactive conversion products. These two products were purified by TLC and HPLC and subjected to mass spectrometry and nuclear magnetic resonance analysis. The interpretation of the spectra was consistent with the structures to be 19-nor-corticosterone and 19-nor-18-hydroxydeoxycorticosterone. The possible biological significance of these two compounds is discussed.

Topics: Adrenal Glands; Animals; Chromatography, High Pressure Liquid; Corticosterone; Desoxycorticosterone; Magnetic Resonance Spectroscopy; Male; Mass Spectrometry; Rats; Rats, Inbred Strains

19-Nor-corticosterone (19-nor-B) was isolated from a pool of urine collected from Wistar-Kyoto (WKY) rats. Identity was established by comparison of chromatographic mobilities with standard 19-nor-B both as the free compound and diacetate derivative. Comparison of the gas chromatographic-mass spectra of the urinary product and standard 19-nor-B as the diacetate following isolation by high pressure liquid chromatography (HPLC) confirmed the identity of the urinary product to be 19-nor-B. This demonstration that 19-nor-B is a naturally occurring product in addition to 19-nor-deoxycorticosterone supports the concept of the existence of a biosynthetic pathway for the formation of the 19-nor-corticosteroids.

Topics: Acetylation; Animals; Chromatography, High Pressure Liquid; Corticosterone; Desoxycorticosterone; Female; Gas Chromatography-Mass Spectrometry; Rats; Rats, Inbred WKY

The effect of absence of the C-19 methyl group from five adrenal steroids has been studied in terms of their affinity for mineralocorticoid (MR) and glucocorticoid receptors (GR). In MR assays, 19-nordeoxycorticosterone and 19-norprogesterone showed 3-fold higher affinity for MR than did their respective parent steroids; 19-norcortisol had 1.5 times the affinity of cortisol for MR. In contrast, corticosterone and 19-nororticosterone showed equal affinity, and 19-noraldosterone showed less than 1% the MR activity of aldosterone. In GR assays, the absence of the C-19 methyl group from progesterone increased GR affinity 3-fold and deoxycorticosterone affinity 1.5-fold. In contrast, the other 19-nor steroids showed decreased affinity vis à vis their parent compounds (19-norcorticosterone, 30%; 19-norcortisol, 10%; 19-noraldosterone, < 1%). These findings suggest that while the 19-nor analogs of 11-deoxy steroids are consistently more active than their parent steroid, the 19-nor 11-oxygenated adrenal steroids show no predictable pattern of binding for MR or GR.

Topics: Aldosterone; Animals; Corticosterone; Desoxycorticosterone; Female; Hydrocortisone; Norprogesterones; Norsteroids; Rats; Receptors, Glucocorticoid; Receptors, Mineralocorticoid; Receptors, Steroid; Structure-Activity Relationship