Table 1.

Overview of key studies concerning the bidirectional crosstalk between GC signalling and HIF mediated pathways.

	Purpose	Results	References
In vitro	DEX effect on HeLa cells under hypoxic conditions	Induction of hypoxia-dependent gene expression	(61)
		Increased HRE-luciferase activity
		The LBD of GR is necessary for HRE-luciferase activity
	Exposure of HK-2 cells or AtT-20 cells to hypoxia	Upregulation of GR mRNA and protein levels due to binding of HIF1α to HREs present in the NR3C1 promotor	(62, 63)
	The effect of GCs on HIF1α function (HepG2 cells)	Attenuation of HIF1α activity upon hypoxia and DEX stimulation as a results of reduced DNA binding and HRE activity associated with problems with HIF1α nuclear translocation	(64)
	Characterization of the hypoxic effect on GR levels and its anti-inflammatory actions in A549 cells	Hypoxia causes a time-dependent downregulation of GR mRNA and protein levels and inhibits GR nuclear translocation	(66, 67, 69)
		The anti-inflammatory effect of DEX is attenuated when A549 cells are exposed to hypoxia and stimulated with LPS or IL-1β
	Effect of chemical hypoxia (CoCl2) and/or DEX on RAW264.7 cells	GILZ is upregulated by hypoxia and is further increased upon DEX stimulation to prevent overactivation of immune cells (macrophages) and overproduction of pro-inflammatory cytokines (inhibition of IL-1β and IL-6 production)	(76)
In vivo	How is hypoxia affecting the endogenous GC pathway and vice versa in zebrafish larvae?	GCs stabilize HIF via pVHL degradation HIF represses GR activity and the GR response to exogenous GCs (e.g. BME) in vhl-/- zebrafish larvae	(81, 82)
		Cortisol levels are reduced by HIF due to repression of POMC expression and intracellular blocking the transcriptional activity of GR
GCs in AMS	Prophylactic effect of GCs when ascending to high altitude	Administration of GCs (DEX and prednisolone) prior to ascending to high altitude reduces the symptoms of AMS (suppresses inflammatory pathways, reduces vascular permeability and vasoconstriction, improves arterial oxygenation and induces a better antioxidant-oxidant balance)	(83–88)
Perinatal hypoxia and GCs	Effect of GCs during perinatal hypoxia	Neonatal hypoxia leads to the activation of the HPA axis in the neonates and causes higher GC levels	(89, 90)
		GCs can have neuroprotective effects on neonatal HI-induced brain damage	(91–93)
		Ideal timing, dose and duration of GCs is necessary to prevent neurotoxic effects	(94, 95)