Table 1.
The Sterol-Sensing Nuclear Hormone Receptors
| NHR | Systematic Name | Physiological Role(s) | Notable Ligandsa | Refs |
|---|---|---|---|---|
| Liver X Receptor (LXR) | NR1H3 (LXRα) NR1H2 (LXRβ) |
Cholesterol sensor and a key regulator of cholesterol, bile acid, and fatty acid homeostasis, in addition to roles in processes of differentiation and immunity. | Oxysterols, including 24(S),25-epoxycholesterol, 22(R)-hydroxycholesterol, 24(S)-hydroxycholesterol Bile Acids (LXRα), including Hyodeoxycholic Acid, Taurohyodeoxycholic Acid, and Cholestenoic Acid Synthetic Ligands include T0901317, GW3965 |
(12–17, 183) |
| Farnesoid X Receptor-α (FXRα) | NR1H4 | Bile acid sensor and master regulator of bile acid metabolism as well as cholesterol and fatty acid homeostasis. Also involved in hepatoprotection, liver regeneration, and inflammation. | Bile Acids, including Chenodeoxycholic Acid, Cholic Acid, Deoxycholic Acid, Lithocholic Acid Synthetic Ligands include GW4064 and 6E-CDCA |
(41) |
| Pregnane X Receptor (PXR) | NR1I2 | Xenobiotic receptor responsive to many compounds including bile acids, involved in hepatoprotection in addition to roles in the inflammatory response and metabolism. | Xenobiotics, including Pregnenolone-16α-carbonitrile (PCN), Phenobarbitol, Rifampicin, and Coumestrol Bile Acids, including Lithocholic and 3-keto-lithocholic Acid Various Steroid Hormones |
(56–57, 60) |
| Constitutive Androstane Receptor (CAR) | NR1I3 | Xenobiotic receptor involved in hepatoprotection as well as liver regeneration and various metabolic processes. | Xenobiotics, including Phenobarbitol, 1,4-Bis[2-(3,5-dichloropyridyloxy)]benzene (TCPOBOP), and 6-(4-Chloro-phenyl)imidazo[2,1b][1,3]thiazole-5-carbaldehyde O-3,4-dichlorobenzyl) oxime (CITGO) Various Steroid Hormones Lithocholic Acid (in vivo) |
(60–62) |
| Vitamin D Receptor (VDR) | NR1I1 | Primarily known as the master regulator of calcium homeostasis, but also involved in differentiation, immunity, and metabolic processes. | 1α,25-dihydroxy-vitamin D3 (Calcitriol) and various synthetic analogs Lithocholic Acid |
(5, 64–65) |
| Drosophila Ecdysone Receptor (EcR) | CG1765 | The Drosophila molting receptor, responsible for key processes of larval molting and metamorphosis. | 20-Hydroxyecdysone | (7) |
| Drosophila Hormone Receptor 96 (DHR96) | CG11783 | Proposed cholesterol sensor of the fly, regulating cholesterol and fatty acid metabolism. | Cholesterol | (8–9) |
| C. elegans DAF-12 | CE27584 | Regulator of the C. elegans dauer diapause decision, DAF-12 governs key developmental and metabolic events and is also required for gonadal longevity. | Dafachronic acids: 25(S),25-3-keto-4-Cholestenoic Acid and 25(S),26-3-keto-7-(5α)-Cholestenoic Acid Bile acid: 24(S)-Cholestenoic Acid |
(10,181, 182) |
a
Not a comprehensive list