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Abstract: FR-PO522

Sexual Dimorphism in Vasopressin Signaling

Session Information

Category: Fluid, Electrolytes, and Acid-Base Disorders

  • 1101 Fluid, Electrolyte, and Acid-Base Disorders: Basic

Authors

  • Grimm, Rick, Johns Hopkins Medicine, Baltimore, Maryland, United States
  • Jung, Hyun Jun, Johns Hopkins Medicine, Baltimore, Maryland, United States
  • Al-Qusairi, Lama, Johns Hopkins Medicine, Baltimore, Maryland, United States
Background

Hyponatremia is a life-threatening condition characterized by decreased body natrium (sodium) concentration due to water retention. For reasons not yet understood, women are more prone to hyponatremic conditions, including exercise-associated hyponatremia, post-operative hyponatremia, and ecstasy-associated hyponatremia. Recent reports suggest that compared to males, female mice concentrate their urine more effectively due to enhanced AQP2 apical membrane localization. It has been suggested that sex hormones affect water balance; however, it is unknown if vasopressin signaling itself exhibits sex-dependent differences.

Methods

The sexual dimorphism in water balance was analyzed in C57BL6J wild-type males and females at basal conditions and after 12 hours of water deprivation. The in-vivo activation of vasopressin signaling was assessed using western blot (WB) and confocal imaging. Plasma copeptin, a surrogate marker of vasopressin secretion, was analyzed using ELISA.

Results

Our data revealed that females exhibit higher urine osmolality at baseline and have an enhanced ability to further concentrate their urine following 12 hours of water deprivation. Plasma copeptin was higher in females compared to males under basal conditions. WB analysis of the renal cortex and medulla in both sexes under basal conditions revealed AQP2 total protein levels were similar between males and females. However, AQP2 phosphorylation at Ser256, in a protein kinase A (PKA) consensus site, was more enhanced in the renal cortex and medulla of females. This is consistent with higher AQP2 apical localization in females as revealed by confocal imaging. To assess a potential sex-dependent activation of vasopressin signaling in the principal cells, we analyzed phospho-PKA substrates in the AQP2-positive cells using phospho-PKA substrate (RRXS/T) antibody. Quantitative analysis of confocal images revealed PKA-substrates were more phosphorylated in the principal cells of females compare to males, indicating more enhanced vasopressin signaling in females.

Conclusion

The sexual dimorphism in water balance is mediated, at least in part, by higher circulating vasopressin levels in females. Subsequently, vasopressin signaling in the collecting duct was more enhanced in females resulting in more robust AQP2 apical translocation.

Funding

  • NIDDK Support