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The biosynthesis of aldosterone.
G P Vinson1, S M Laird, B J Whitehouse
1Department of Biochemistry, Basic Medical Sciences, Queen Mary and Westfield College, London, England.
The Journal of Steroid Biochemistry and Molecular Biology
|November 1, 1991
Summary
Aldosterone production in rats may not use corticosterone as an intermediate. Instead, stored 18-hydroxydeoxycorticosterone in adrenal membranes might be the direct precursor for aldosterone synthesis.
Area of Science:
- Endocrinology
- Molecular Biology
- Steroidogenesis
Background:
- Cellular mechanisms of aldosterone biosynthesis are not fully understood.
- Existing models suggest corticosterone as a key intermediate, but experimental data show inconsistencies.
- Aldosterone secretion dynamics in rat adrenal preparations challenge the corticosterone intermediate hypothesis.
Purpose of the Study:
- To investigate the cellular mechanisms and precursors involved in aldosterone biosynthesis in rat adrenal tissue.
- To identify the immediate steroid substrate for aldosterone production.
- To explore the role of membrane-bound steroids and protein kinase C in regulating aldosterone synthesis.
Main Methods:
- Comparison of aldosterone formation from endogenous vs. radioactive precursors ([3H]pregnenolone) in whole glomerulosa tissue.
- Analysis of aldosterone and corticosterone response dynamics in situ perfused rat adrenal glands stimulated by ACTH.
- Localization and characterization of steroid pools in rat adrenal glomerulosa tissue and plasma membrane fractions.
- Assessment of aldosterone production in dispersed glomerulosa cells versus intact tissue.
- Investigation of trypsin's effect on aldosterone production and protein kinase C translocation.
Main Results:
- Aldosterone is more readily formed from endogenous precursors than added [3H]pregnenolone in whole glomerulosa tissue.
- Aldosterone responses to ACTH stimulation are faster than corticosterone responses in perfused glands, indicating a separate precursor.
- 18-hydroxydeoxycorticosterone (18-OH-DOC) is the only steroid stored in significant amounts in rat adrenal glomerulosa, localized to plasma membranes.
- Dispersed glomerulosa cells, lacking the membrane 18-OH-DOC pool, produce less aldosterone relative to corticosterone.
- Trypsin stimulates aldosterone production and protein kinase C translocation to the plasma membrane in intact glomerulosa but not in dispersed cells.
Conclusions:
- The data suggest that freshly synthesized corticosterone is not a major intermediate in rat aldosterone biosynthesis.
- Stored 18-hydroxydeoxycorticosterone (18-OH-DOC) in adrenal glomerulosa plasma membranes is likely the immediate precursor for aldosterone.
- Protein kinase C activation may mobilize membrane-sequestered 18-OH-DOC, facilitating its conversion to aldosterone in the rat adrenal zona glomerulosa.