Mouse Adrenal Sexual Dimorphic Responses to Alterations in Sodium Diet

Presentation Number: SUN 537
Date of Presentation: April 2nd, 2017

Jessica A. Lora*, Matthew J. Taylor, Adina F. Turcu and William E. Rainey
The University of Michigan, Ann Arbor, MI

Abstract

Introduction: The adrenal gland plays a critical role in sodium balance and its production of aldosterone in response to a deficient sodium diet is critical for survival. While many studies have shown the effects of a sodium deficient diet on mouse aldosterone production, none have investigated sex differences in the adrenal response. The goal of the current study was to determine if there are sexual dimorphic adrenal responses to sodium deficient diet.

Methods: Starting at 9-10 weeks of age, adult female and male C57BL/6J mice were separated into two treatment groups: control diet (normal chow, 0.49% NaCl) and sodium deficient diet (0.02% NaCl). After 6 days, plasma was collected for steroid analysis using LC-MS/MS (for each sex, n=6 for control, n=7 for sodium deficient). Adrenal glands were also collected for mRNA analysis using RT-qPCR (n=12 control for each sex, n=7 female sodium deficient, n=13 male sodium deficient) and protein expression studies using immunofluorescence (n=3 for each group).

Results: LC-MS/MS analysis revealed an elevation in plasma aldosterone in mice provided a sodium deficient diet in both males and females (3.2±1.25 fold and 12.1±2.1 fold, respectively). There was also significantly increased adrenal Cyp11b2 mRNA gene expression in both treated male and female mice (3.6±0.52 fold and 7.7±1.07 fold, respectively), as well as increased Cyp11b2 protein expression localized in the zona glomerulosa in the sodium deficient group compared to controls in both sexes. There were no significant changes in corticosterone, the predominant mouse glucocorticoid, in either male or female mice between control or sodium deficient diets. Most notably, this study revealed a significantly higher response to sodium deficient diet in females compared to males in both plasma aldosterone levels (p< 0.05) and adrenal Cyp11b2mRNA expression (p<0.01).

Conclusion: The current study suggests a sexual dimorphic response to the renin-angiotensin-aldosterone system in which female adrenals are more responsive than male adrenals. The mechanism for female hyper-responsiveness is not known, but these findings support previous studies where mouse models of primary aldosteronism showed sexual dimorphic responses. Finally, the described sex differences further support the need to include/compare both sexes for mouse adrenal research.

 

Nothing to Disclose: JAL, MJT, AFT, WER