Aldosterone exerts its slow (genomic) effect on principal cells by inducing synthesis of which protein(s) that increase renal Na⁺ retention?

• A Renin directly in collecting duct cells — producing local angiotensin II to activate ENaC
• B AQP2 water channels in principal cells, reducing urine volume but not directly increasing Na⁺ transport
• C SGK1 (serum/glucocorticoid-regulated kinase 1) → phosphorylates and inhibits NEDD4-2 → prevents ubiquitin-mediated internalization of ENaC; also induces α-ENaC subunit and Na-K-ATPase α1 subunit synthesis ✓
• D Vasopressin (ADH) via V2 receptor stimulation, which then increases ENaC activity

Explanation

Aldosterone binds mineralocorticoid receptors (MR) in principal cells and, after nuclear translocation, induces gene transcription. Key genomic targets include SGK1 (serum- and glucocorticoid-regulated kinase 1), which phosphorylates NEDD4-2 (an E3 ubiquitin ligase), preventing it from ubiquitinating ENaC and targeting it for endocytosis — thereby increasing ENaC surface expression. Aldosterone also directly increases α-ENaC subunit mRNA and Na-K-ATPase pump subunit synthesis, creating more pumps to handle the increased Na⁺ load. The acute (non-genomic) aldosterone effects via GPCR/PLC occur within minutes but the classical genomic SGK1 mechanism explains the 1-2 hour latency.

Reference: Guyton & Hall, Textbook of Medical Physiology, 14th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.