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Steroid hormone release as well as renal water and electrolyte excretion of mice expressing PKB/SGK-resistant GSK3

  • Signaling and Cell Physiology
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Abstract

Insulin and insulin-like growth factor (IGF1) participate in the regulation of renal electrolyte excretion. Insulin- and IGF1-dependent signaling includes phosphatidylinositide-3 (PI3)-kinase, phosphoinositide-dependent kinase PDK1 as well as protein kinase B (PKB) and serum and glucocorticoid inducible kinase (SGK) isoforms, which in turn phosphorylate and thus inhibit glycogen synthase kinase GSK3α,β. Replacement of the serines in the PKB/SGK consensus sequences by alanine (gsk3 KI) confers resistance of GSK3 to PKB/SGK. To explore the role of PKB/SGK-dependent inhibition of GSK3 in the regulation of water/electrolyte metabolism, mice carrying the PKB/SGK resistant mutant (gsk3 KI) were compared to their wild-type littermates (gsk3 WT ). Body weight was similar in gsk3 KI and gsk3 WT mice. Plasma aldosterone at 10 a.m. and corticosterone concentrations at 5 p.m. were significantly lower, but 24-h urinary aldosterone was significantly higher, and corticosterone excretion tended to be higher in gsk3 KI than in gsk3 WT mice. Food and water intake, fecal excretion, glomerular filtration rate, urinary flow rate, urine osmolarity, as well as urinary Na+, K+, urea excretion were significantly larger, and plasma Na+, urea, but not K+ concentration, were significantly lower in gsk3 KI than in gsk3 WT mice. Body temperature was significantly higher in gsk3 KI than in gsk3 WT mice. When allowed to choose between tap water and saline, gsk3 WT mice drank more saline, whereas gsk3 KI mice drank similar large volumes of tap water and saline. During high-salt diet, urinary vasopressin excretion increased to significantly higher levels in gsk3 KI than in gsk3 WT mice. After water deprivation, body weight decreased faster in gsk3 KI than in gsk3 WT mice. Blood pressure, however, was significantly higher in gsk3 KI than in gsk3 WT mice. The observations disclose a role of PKB/SGK-dependent GSK3 activity in the regulation of steroid hormone release, renal water and electrolyte excretion and blood pressure control.

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Acknowledgments

The authors express their gratitude to Dario Alessi for providing the gsk3 KI mice. The authors further acknowledge the support by the DFG (GRK 1302/1).

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Authors and Affiliations

  1. Department of Physiology, University of Tübingen, Gmelinstr. 5, 72076, Tübingen, Germany

    Krishna M. Boini, Madhuri Bhandaru & Florian Lang

  2. Department of Anatomy, University of Tübingen, Oesterbergstr. 3, 72074, Tübingen, Germany

    Andreas Mack

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  1. Krishna M. Boini
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Correspondence to Florian Lang.

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Krishna M. Boini and Madhuri Bhandaru contributed equally and thus share first authorship.

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Boini, K.M., Bhandaru, M., Mack, A. et al. Steroid hormone release as well as renal water and electrolyte excretion of mice expressing PKB/SGK-resistant GSK3. Pflugers Arch - Eur J Physiol 456, 1207–1216 (2008). https://doi.org/10.1007/s00424-008-0483-8

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