Renal 21-hydroxylation of 19-hydroxy-progesterone to 19-hydroxy-deoxycorticosterone.
19-Nor-deoxycorticosterone (19-nor-DOC) is a mineralocorticoid present in both rat and human urine, and it is elevated in some forms of experimental and human hypertension. Although the exact steps in the biosynthesis of 19-nor-DOC are uncertain, it is probably produced from a 19-oxygenated derivative of DOC, which undergoes 19-desmolation in the kidney. Since DOC biosynthesis is partly due to renal 21-hydroxylation of progesterone (Prog), we sought to determine whether a parallel pathway could exist for the biosynthesis of 19-hydroxy-DOC, a precursor to 19-nor-DOC. In order to test this hypothesis, authentic 19-hydroxy-progesterone was incubated with homogenized renal tissues from either rat or human sources. Formation of 19-hydroxy-DOC was found to be the major metabolite in both rat and human incubations, as demonstrated by an HPLC retention time identical to authentic 19-hydroxy-DOC. 19-Hydroxy-DOC formation was further verified by GC/MS analysis with highly sensitive selected ion recording. Since it has been demonstrated that the placenta can convert progesterone to 19-hydroxy-progesterone, the renal 21-hydroxylation of 19-hydroxy-progesterone to 19-hydroxy-DOC could be an alternate pathway of 19-nor-DOC production especially during pregnancy.
Griffing
G T
GT
Evans Memorial Department of Clinical Research, University Hospital, Boston University Medical Center, MA 02118.
Holbrook
M M
MM
Bencsath
F A
FA
Melby
J C
JC
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003900:Desoxycorticosterone / Q000031:analogs & derivatives* / Q000096:biosynthesis; D006801:Humans; D006900:Hydroxylation; D006908:Hydroxyprogesterones / Q000378:metabolism*; D066298:In Vitro Techniques; D007668:Kidney / Q000378:metabolism*; D013058:Mass Spectrometry; D051381:Rats
D006908:Hydroxyprogesterones; C027855:19-hydroxydeoxycorticosterone; D003900:Desoxycorticosterone; C057411:19-hydroxyprogesterone