Effects of prednisolone administration on clock gene expression and indices of circadian rhythms in healthy human subjects

Simon Boggild Hansen; Jelena Stankovic; Henrik Oster; Niels Jessen; Jens Otto Jorgensen

doi:10.1530/endoabs.110.P101

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Endocrine Abstracts (2025) 110 P101 | DOI: 10.1530/endoabs.110.P101

ECEESPE2025 Poster Presentations Adrenal and Cardiovascular Endocrinology (169 abstracts)

Effects of prednisolone administration on clock gene expression and indices of circadian rhythms in healthy human subjects

Simon Bøggild Hansen ^1,2,3 , Jelena Stankovic ^1,2,3 , Henrik Oster ⁴ , Niels Jessen ³ & Jens Otto Jørgensen ^1,2

Author affiliations

¹Aarhus University Hospital, Department of Medical Endocrinology and Internal Medicine, Aarhus N, Denmark; ²Aarhus University, Institute of Clinical Medicine, Aarhus N, Denmark; ³Steno Diabetes Centre Aarhus, Aarhus University Hospital, Aarhus N, Denmark; ⁴University of Lübeck, Center of Brain Behaviour and Metabolism, Lübeck, Germany

JOINT3916

Background: States of glucocorticoid (GC) excess and circadian clock disruption disorders – as observed in shift workers and following chronic stress and sleep deprivation – both confer an increased risk of developing abdominal obesity, type 2 diabetes and cardiovascular disease. Animal studies have demonstrated that GCs regulate circadian clocks providing a potential mechanism for GC side effects however, experimental data in human models are sparse.

Objective: To investigate the impact of exogenous GC exposure in human subjects on clock gene expression in muscle and fat in concomitance with assessment of circadian variations in peripheral interstitial glucose levels, blood pressure, cortisol levels and sleep quality.

Design: Randomized double-blinded crossover trial with ten healthy males aged 18–34.

Intervention: Prednisolone 25 mg/day in two daily doses or placebo in random order for five days with 6 week washout.

Results: During placebo treatment, an expected large difference was observed between morning and evening expression levels of all four clock genes investigated in adipose tissue and skeletal muscle (table). Prednisolone profoundly flattened the diurnal change in expression levels of all genes. Prednisolone treatment led to increased nocturnal interstitial glucose (placebo 6.6±0.8 vs prednisolone 8.2±0.9 mmol/l, P<0.001) and elevated nocturnal nadir of systolic blood pressure (placebo 116±7 vs. prednisolone 123±14, P=0.05).


	Placebo		Prednisolone
Parameter	Fold difference morning vs evening	P-value	Fold difference morning vs evening	P-value
Adipose tissue – (2⁻ ^ΔΔCT)
Per3	3.3 (2.4 to 4.5)	<0.001	1.3 (0.9 to 1.8)	0.11
Reverb-Beta	3 (2.3 to 3.9)	<0.001	1.3 (1 to 1.7)	0.04
Bmal1	0.3 (0.2 to 0.4)	<0.001	1 (0.7 to 1.4)	0.99
Npas2	0.4 (0.3 to 0.6)	<0.001	0.8 (0.6 to 1.1)	0.20
Skeletal muscle – (2⁻ ^ΔΔCT)
Per3	2.6 (2 to 3.5)	<0.001	1.1 (0.8 to 1.4)	0.59
Reverb-Beta	1.8 (1.3 to 2.3)	<0.001	0.9 (0.7 to 1.2)	0.56
Bmal1	0.4 (0.3 to 0.6)	<0.001	0.7 (0.5 to 1)	0.05
Npas2	0.5 (0.3 to 0.8)	<0.01	0.7 (0.5 to 1.2)	0.20

Conclusion: Prednisolone twice daily abolished the normal fluctuations in the expression levels of core clock genes in skeletal muscle and adipose tissue. This was accompanied by disturbed sleep, and altered daily patterns of glucose levels and blood pressure. Our findings add important human data supporting GC-induced circadian disruption in metabolic tissues.