Fludrocortisone

Fludrocortisone (9α-Fludrocortisone) is an orally active mineralocorticoid and glucocorticoid receptor agonist. Fludrocortisone suppresses pro-inflammatory cytokine expression, reduces CCL2, IL-6, IL-8 levels, upregulates mineralocorticoid receptor (MR) expression, induces PI3K/Akt, GSK-3β, CREB, ERK1/2, mTOR phosphorylation, blocks Tau hyperphosphorylation, prevents apoptosis, promotes survival and proliferation, enhances renal sodium and water transport, increases plasma volume and blood pressure, reduces plasma potassium and renin activity, stimulates erythropoietin expression, modulates uterine receptivity genes, and reverses PP242-induced MUC1 upregulation. Fludrocortisone can be used for the research of congenital adrenal hyperplasia, postural hypotension, and adrenal insufficiency^{[1][2][3][4][5][6]}. In Vitro:Fludrocortisone (0.01-10 μg/μL; 12 h) is non-cytotoxic to MIO-M1, ARPE19, and 661W human retinal cell lines at concentrations up to 1 μg/μL, with reduced viability only seen at 10 μg/μL in MIO-M1 and 661W cells^[1].
Fludrocortisone (1 μg/μL; 12 h) potently suppresses IL-1β- and TNF-α-induced CCL2, IL-6, and IL-8 mRNA expression in MIO-M1 human Müller glial cells^[1].
Fludrocortisone (1 μM; 24 h) increases mineralocorticoid receptor
(MR) gene expression in AHPs without altering glucocorticoid receptor (GR) expression^[2].
Fludrocortisone (0.5-2 μM; 24 h) promotes survival, proliferation, and reduces apoptosis in growth factor-deprived AHPs, with 1 μM being the optimal concentration^[2].
Fludrocortisone (1 μM) activates cAMP/PKA/CREB signaling in AHPs, which is required for its pro-survival and pro-proliferative effects^[2].
Fludrocortisone (1 μM) activates PI3K/Akt and mTOR/p70S6K signaling, and inactivates GSK-3β, which is required for its protective effects in growth factor-deprived AHPs^[2].
Fludrocortisone (1 μM) protects AHPs from Aβ_1-42-induced toxicity by promoting survival, proliferation, reducing apoptosis, restoring Akt/GSK-3β phosphorylation, and blocking Tau hyperphosphorylation^[2].
Fludrocortisone (4-6 h) stimulates Epo, HIF2α, HIF1α, and PHD2 mRNA expression in microdissected rat nephron segments and mouse kidney nephron segments and peritubular cells, with significant increases relative to basal conditions^[5].
Fludrocortisone (6 h, 72 h) significantly increases Epo protein expression in rat renal cortex but not in rat liver, relative to basal conditions^[5].
Fludrocortisone (4-6 h) stimulates Epo protein production in mouse MAL, CCD, and OMCD, with specific upregulation in type A intercalated cells of the collecting ducts, and effects diminish to basal levels by 72 h^[5]. In Vivo:Fludrocortisone (1 μg/μL; intravitreal injection (3 μL); single dose) exerts neuroprotective effects in a mouse photo-oxidative retinal degeneration model, preserving retinal structure and function, reducing photoreceptor apoptosis, and inhibiting macrophage infiltration^[1].
Fludrocortisone (1.5 mg/kg; i.p.; twice on Days 4 and 5 of pregnancy) modulates uterine receptivity in pregnant BALB/c mice by upregulating LIF, HB-EGF, Msx.1, and miRNA Let-7a, and activating the ERK1/2-mTOR pathway without altering MUC1 or miRNA 223-3p expression^[4].
Fludrocortisone (1.5 mg/kg; i.p.; twice on Days 4 and 5 of pregnancy) co-administered with PP242 (30 mg/kg) reverses PP242-induced MUC1 upregulation and restores upregulation of key uterine receptivity genes (LIF, HB-EGF, Msx.1, miRNA Let-7a) in pregnant BALB/c mice^[4].
Fludrocortisone (2.5 mg/100 g BW/day; i.p.; daily) stimulates renal Epo mRNA expression (peak at 4 hours) and Epo protein expression (at 6 and 72 hours) in male Sprague Dawley rats, with a statistically significant increase in plasma Epo concentration at 6 hours post-administration^[5].