Vitamin D auto-/paracrine system activity in rat liver depending on vitamin D status

13.04.2026   Uncategorized

M. Veliky1, I. Shymanskyi1*, O. Lisakovska1, A. Khomenko1,
Yu. Parkhomenko1, Ye. Kucheriavyi2, V. Bilous3

1Department of Biochemistry of Vitamins and Coenzymes, Palladin Institute
of Biochemistry, National Academy of Sciences of Ukraine, Kyiv;
2Department of Protein Structure and Function, Palladin Institute
of Biochemistry, National Academy of Sciences of Ukraine, Kyiv;
3Department of Enzyme Chemistry and Biochemistry, Palladin Institute
of Biochemistry, National Academy of Sciences of Ukraine, Kyiv;
*e-mail: ihorshym@gmail.com

Received: 11 January 2026; Revised: 19 February 2026;
Accepted: 03 April 2026; Available on-line: April 2026

The liver plays a central role in vitamin D metabolism, facilitating its primary activation and systemic transport. However, the molecular mechanisms of vitamin D hydroxylation and reception involving the auto-/paracrine vitamin D system in the liver remain insufficiently understood. The aim of the study was to evaluate cytochrome P450 (CYP) enzymes and vitamin D receptor (VDR) expression in the liver of rats with nutritional vitamin D3 deficiency and after therapeutic treatment. Vitamin D deficiency was modeled by maintaining female Wistar rats on vitamin D-free diet for 60 days. The treatment was performed by cholecalciferol (1000 IU/kg bw) oral administration for 30 days. Serum 25(OH)D level was determined by ELISA, 25-hydroxylase activity in hepatocytes was evaluated using [3H]cholecalciferol as a substrate. The level of CYP2R1, CYP27A1, CYP27B1, CYP24A1 and VDR proteins in the liver was studied via Western blot analysis. A 60-day vitamin D-deficiency led to a critical decrease in 25(OH)D level in the serum, significant increase in 25-hydroxylase activity, CYP2R1 and VDR expression, against the background of reduced CYP24A1 level, in the liver. Vitamin D3 administration ensured the restoration of serum 25(OH)D, as well as the level of the molecular markers­ of vitamin D transformation and reception in the liver, except for CYP27B1, which maintained mode­rately elevated expression. Thus, the metabolic adaptation under vitamin deficiency was manifested through compensatory enhancement in vitamin D synthesis and increased receptor sensitivity against the background of suppressed catabolic pathways. Nutritional correction effectively restored the balance in the auto-/paracrine vitamin D system, ensuring stable homeostasis.

Keywords: , , , , , , , ,

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