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Biological sex modifies aldosterone's secretion at a cellular level
Shadi K Gholami1, Chee Sin Tay1,2, Jessica M Lee1,2
1Division of Endocrinology, Diabetes, and Hypertension, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
The Journal of Endocrinology
|October 13, 2021
Summary
Sex differences impact aldosterone (ALDO) biosynthesis and circulating levels. Males have higher basal ALDO, while females exhibit greater ALDO response to stimulation due to enhanced early biosynthesis steps.
Area of Science:
- Endocrinology
- Molecular Biology
- Physiology
Background:
- Inconsistent reports exist regarding sex-based differences in aldosterone (ALDO) levels.
- Estrogen and its receptor may influence mineralocorticoid receptor (MR) activity and ALDO secretagogue levels, contributing to these inconsistencies.
Purpose of the Study:
- To investigate sex-specific differences in aldosterone biosynthesis pathways.
- To elucidate the molecular mechanisms underlying variable ALDO levels between sexes.
Main Methods:
- In vivo measurement of plasma renin activity and ALDO in male and female rats.
- Ex vivo assessment of zona glomerulosa (ZG) cell function, including early (StAR, CYP11A1) and late (CYP11B2) biosynthesis steps.
- Evaluation of the mineralocorticoid receptor (MR)-mediated ultrashort feedback loop in ZG cells.
Main Results:
- Males exhibited higher plasma renin activity and basal ALDO levels in vivo.
- Females showed increased expression and activity of early ALDO biosynthesis enzymes (StAR, CYP11A1) ex vivo.
- Despite differences in early steps, CYP11B2 expression/activity and MR feedback were similar between sexes; basal ALDO was lower in females ex vivo, but their ALDO response to angiotensin II was higher.
Conclusions:
- Sex significantly modulates aldosterone biosynthesis, with distinct molecular profiles contributing to observed level variations.
- Higher basal ALDO in males is likely due to elevated secretagogue levels.
- Enhanced early biosynthesis in females underlies their greater ALDO production upon acute stimulation, explaining inconsistent clinical findings.
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