Premium
HYPOTHESIS: ALDOSTERONE IS SYNTHESIZED BY AN ALTERNATIVE PATHWAY DURING SEVERE SODIUM DEPLETION. ‘A NEW WINE IN AN OLD BOTTLE’
Author(s) -
Boon Wah Chin,
McDougall John G,
Coghlan John P
Publication year - 1998
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.1998.tb02365.x
Subject(s) - aldosterone , endocrinology , medicine , hydroxylation , enzyme , chemistry , biosynthesis , steroid 11 beta hydroxylase , angiotensin ii , sodium , biology , biochemistry , hormone , steroid , blood pressure , organic chemistry
SUMMARY 1. The last three steps of aldosterone biosynthesis, 11β‐hydroxylation, 18‐hydroxylation and 18‐oxidation, have been demonstrated to be catalysed by one enzyme, which is the cytochrome P450np (CYP11B) in cow, pig, sheep and bullfrog or cytochrome P450aldo (CYP11B2) in rat, human, mouse and hamster. 2. The related enzyme P45011β (CYP11B1) from rat, human, mouse and hamster adrenals displays 11β‐hydroxylation and 18‐hydroxylation activities, but not 18‐oxidation activity in vitro. No such enzyme has been reported in the cow, pig or sheep to date. 3. Data showing the dissociation of aldosterone secretion from plasma angiotensin II (Angll) levels indicate the presence of other factor(s) that regulate aldosterone biosynthesis in response to changes in body sodium status. Thus, we propose the existence of a ‘sodium status factor’ that regulates aldosterone biosynthesis in addition to Angll, K, + adrenocorticotropic hormone and atrial natriuretic peptide. 4. We propose that during severe sodium deficiency there is a switch in the aldosterone pathway to a pathway using 18‐hydroxy‐deoxycorticosterone (18‐OH‐DOC) rather than corti‐costerone as an intermediate. This switch may be mediated via the putative ‘sodium status factor’. 5. Two models of the hypothesis will be discussed in this paper: (i) a ‘one‐enzyme’ model; and (ii) a ‘two‐enzyme’ model. 6. The one‐enzyme model proposes that P450aldo (P45011β as in the case of the cow, sheep and pig) changes its enzymatic activity during severe sodium deficiency (i.e. switching to the alternative aldosterone biosynthesis pathway). 7. The two‐enzyme model proposes that, under normal circumstances, P450 aldo synthesizes aldosterone from deoxycorticosterone, while during severe sodium deficiency the P450up provides the substrate (i.e 18‐OH‐DOC) for the P450 aldo .