The biosynthesis of aldosterone.
The cellular mechanisms for aldosterone biosynthesis are incompletely understood. Although the enzymes involved are now well characterized, the dynamics of aldosterone secretion in a variety of rat adrenal preparations are not consistent with the concept that freshly synthesized corticosterone is an important intermediate. In whole glomerulosa tissue preparations, aldosterone is more readily formed from endogenous precursors than from an added radioactive precursor, such as [3H]pregnenolone, and in the in situ perfused gland preparation, aldosterone responses to stimulation, for example by ACTH, are significantly more rapid than those of corticosterone, suggesting a tissue source of steroid substrate for aldosterone production other than corticosterone. The only steroid which is stored in rat adrenal glomerulosa tissue to any extent is 18-hydroxydeoxycorticosterone (18-OH-DOC), and this pool has been located in plasma membrane fractions. It is lost on preparation of collagenase dispersed glomerulosa cells. Since dispersed glomerulosa cell preparations produce significantly less aldosterone, relative to corticosterone, than incubated intact whole glomerulosa, it is plausible that this tissue pool (which is not found in the inner zones) is the immediate precursor for aldosterone formation. Further evidence shows that trypsin, which stimulates aldosterone (and 18-hydroxycorticosterone) production in rat intact glomerulosa tissue, but not in dispersed cells, stimulates translocation of protein kinase C to the plasma membrane. It is plausible that one function of protein kinase C in the rat adrenal zona glomerulosa is to mobilize membrane sequestered 18-OH-DOC for conversion to aldosterone.
Vinson
G P
GP
Department of Biochemistry, Basic Medical Sciences, Queen Mary and Westfield College, London, England.
Laird
S M
SM
Whitehouse
B J
BJ
Teja
R
R
Hinson
J P
JP
D000450:Aldosterone / Q000096:biosynthesis*; D000818:Animals; D002384:Catalysis; D003345:Corticosterone / Q000096:biosynthesis; D019405:Cytochrome P-450 CYP11B2; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D003900:Desoxycorticosterone / Q000031:analogs & derivatives / Q000096:biosynthesis; D066298:In Vitro Techniques; D051381:Rats; D013250:Steroid Hydroxylases / Q000378:metabolism; D014357:Trypsin / Q000502:physiology; D015384:Zona Glomerulosa / Q000201:enzymology / Q000378:metabolism*
C042509:18-hydroxydeoxycorticosterone; D003900:Desoxycorticosterone; D000450:Aldosterone; D003577:Cytochrome P-450 Enzyme System; D013250:Steroid Hydroxylases; D019405:Cytochrome P-450 CYP11B2; D014357:Trypsin; D003345:Corticosterone