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Sexual Dimorphic Pattern of Renal Transporters and Electrolyte Homeostasis.

ABSTRACT: Compared with males, females have lower BP before age 60, blunted hypertensive response to angiotensin II, and a leftward shift in pressure natriuresis. This study tested the concept that this female advantage associates with a distinct sexual dimorphic pattern of transporters along the nephron. We applied quantitative immunoblotting to generate profiles of transporters, channels, claudins, and selected regulators in both sexes and assessed the physiologic consequences of the differences. In rats, females excreted a saline load more rapidly than males did. Compared with the proximal tubule of males, the proximal tubule of females had greater phosphorylation of Na⁺/H⁺ exchanger isoform 3 (NHE3), distribution of NHE3 at the base of the microvilli, and less abundant expression of Na⁺/Pi cotransporter 2, claudin-2, and aquaporin 1. These changes associated with less bicarbonate reabsorption and higher lithium clearance in females. The distal nephrons of females had a higher abundance of total and phosphorylated Na⁺/Cl^- cotransporter (NCC), claudin-7, and cleaved forms of epithelial Na⁺ channel (ENaC) ? and ? subunits, which associated with a lower baseline plasma K⁺ concentration. A K⁺-rich meal increased the urinary K⁺ concentration and decreased the level of renal phosphorylated NCC in females. Notably, we observed similar abundance profiles in female versus male C57BL/6 mice. These results define sexual dimorphic phenotypes along the nephron and suggest that lower proximal reabsorption in female rats expedites excretion of a saline load and enhances NCC and ENaC abundance and activation, which may facilitate K⁺ secretion and set plasma K⁺ at a lower level.

SUBMITTER: Veiras LC

PROVIDER: S-EPMC5698077 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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Sexual Dimorphic Pattern of Renal Transporters and Electrolyte Homeostasis.

Veiras Luciana C LC Girardi Adriana C C ACC Curry Joshua J Pei Lei L Ralph Donna L DL Tran An A Castelo-Branco Regiane C RC Pastor-Soler Nuria N Arranz Cristina T CT Yu Alan S L ASL McDonough Alicia A AA

Journal of the American Society of Nephrology : JASN 20170803 12

Compared with males, females have lower BP before age 60, blunted hypertensive response to angiotensin II, and a leftward shift in pressure natriuresis. This study tested the concept that this female advantage associates with a distinct sexual dimorphic pattern of transporters along the nephron. We applied quantitative immunoblotting to generate profiles of transporters, channels, claudins, and selected regulators in both sexes and assessed the physiologic consequences of the differences. In rat ...[more]

PMID: 28774999

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Project description:Males and females exhibit differences in the incidence of many major diseases including auto-immune diseases, hepatocellular carcinoma, diabetes, and osteoporosis, which all have important inflammatory components in their etiology. Glucocorticoids are the primary physiological anti-inflammatory hormone in all mammals and synthetic derivatives of these hormones are widely prescribed as anti-inflammatory agents irrespective of gender. Surprisingly we report a marked sexually dimorphic regulation of gene expression by glucocorticoids in the rat liver. Eight distinct patterns of glucocorticoid regulated genes were identified and two revealed genes that respond to glucocorticoid treatment in both sexes in opposite directions (anti-correlated genes. We also identified gender-specific groups of genes regulated by glucocorticoids. Pathways analysis identified sex-specific glucocorticoid regulated gene expression in several canonical pathways that have been implicated in human disease in which disease susceptibility is sex-biased. For example, comparison of number of genes involved in inflammatory disorders between sexes, revealed 84 additional glucocorticoid responsive genes in the male rat. Our data suggests that glucocorticoids thorough sexually-dimorphic regulation of gene expression modulate gender specific homeostatic functions in male and female liver. Adult males and females adrenalectomized Sprague-Dawley rats (8-10 weeks of age) (females Distrous 1) were treated with vehicle (Phosphate Buffered Saline – 400 µl) or Dexamethasone (1mg/Kg i.p.) purchased from Steraloids (Newport, RI). Liver was harvested 6 hours after treatment and kept in RNA later solution at 4oC over night. Samples were frozen and stored at -80oC. Three replicate microarrays were completed for each group (male vehicle, male dexamethasone, female vehicle and female dexamethasone) for a total of 12 microarrays. Each microarray was hybridized using a pooled RNA sample, and each pool was created from equal amounts of total RNA from three independent RNA samples, representing individual animals (n=9 animals per group). This approach provides appropriate biological replication within the constraints of a limiting number of microarrays (C. Kendziorski, R. A. Irizarry, K. S. Chen, J. D. Haag, M. N. Gould, Proc Natl Acad Sci U S A 102, 4252 Mar 22, 2005).

Dataset Information

Sexual Dimorphic Pattern of Renal Transporters and Electrolyte Homeostasis.

Publications

Sexual Dimorphic Pattern of Renal Transporters and Electrolyte Homeostasis.

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