Versatile steroid molecules at the end of the aldosterone pathway

18-hydroxycorticosterone converts spontaneously and reversibly to a variety of less polar forms and derivatives, some of which are precursors to aldosterone. In particular, 21-hydroxy-11β,18-oxido-4-pregnene-3,20-dione (18-DAL) is hydroxylated to aldosterone with high yields in the presence of malat...

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Autores principales: Lantos, C.P., Damasco, M.C., Aragonés, A., Ceballos, N.R., Burton, G., Cozza, E.N.
Formato: JOUR
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Acceso en línea:http://hdl.handle.net/20.500.12110/paper_00224731_v27_n4-6_p791_Lantos
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Sumario:18-hydroxycorticosterone converts spontaneously and reversibly to a variety of less polar forms and derivatives, some of which are precursors to aldosterone. In particular, 21-hydroxy-11β,18-oxido-4-pregnene-3,20-dione (18-DAL) is hydroxylated to aldosterone with high yields in the presence of malate and NADP+ at pH 4.8.18-DAL also behaves as a metabolic intermediate between 18-OH-B and aldosterone accorcling to time-course and trapping experiments. Consequently, the final steps of the aldosterone pathway at pH 4.8 could be identified as 18-OH-B,18-DAL and aldosterone, in this sequence. The submitochondrial distribution of aldosterone biosynthesis is compatible with this postulate. The work also shows that some forms of 18-OH-B are promoters of hydrogen transport in renal tubuli and that this regulation may be independent of sodium reabsorption. These results suggest a regulatory model, new in steroid biology, accorcling to which steroid molecules bearing an oxidized angular C18-methyl may undergo structural changes between precursor ("P") and hormonal ("H") forms in response to homeostatic requirements. © 1987.