Effect of sex hormones on the expression of genes encoding organic anion-transporting polypeptides OATP1B1/OATP1B3 in vitro

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Abstract

Introduction. OATP1B1 and OATP1B3 are influx proteins belonging to the SLC transporter family and providing substrate transport into hepatocytes. The mechanisms of their regulation are currently being actively studied.

Aim. To study the effect of sex hormones on the expression of the SLCO1B1 and SLCO1B3 genes encoding OATP1B1 and OATP1B3, respectively.

Material and methods. The study was performed on the HepG2 cell line. Estradiol, progesterone, and testosterone were added to the cells at concentrations of 1 nM, 10 nM, 100 nM, 1 μM, 10 μM, 100 μM and incubated for 24 h. After incubation, total RNA was isolated and gene expression was tested by real-time polymerase chain reaction.

Results. Estradiol at concentrations of 10 and 100 μM increased the expression of the SLCO1B1 gene encoding OATP1B1 by 50.9% (p=0.027) and 60.2% (p=0.009), respectively. Testosterone at a concentration of 1 μM increased the expression of the SLCO1B1 gene by 53.2% (p=0.014), at a concentration of 10 μM – by 62.7% (p=0.004), at a concentration of 100 μM – by 66.7% (p=0.0026). Estradiol at concentrations of 1, 10 and 100 μM increased the expression of the SLCO1B3 gene by 80.3% (p=0.0021), 115.6% (p<0.001) and 115.5% (p<0.001), respectively. Testosterone at concentrations of 1, 10 and 100 μM increased the expression of SLCO1B3 by 53.2% (p=0.029), 62.7% (p=0.007) and 66.7% (p=0.032), respectively, compared to the control.

Conclusion. Thus, it was established that estradiol and testosterone increase the expression of the SLCO1B1 and SLCO1B3 genes, and progesterone does not affect them.

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About the authors

А. А. Slepnev

Ryazan State Medical University named after Academician I.P. Pavlov

Author for correspondence.
Email: a.slepnev@rzgmu.ru
ORCID iD: 0000-0003-0696-6554

Ph.D. (Biol.), Associate Professor, Associate Professor of the Department of Pharmacology

Russian Federation, Vysokovoltnaya str., 9, Ryazan, 390026

Yu. V. Abalenikhina

Ryazan State Medical University named after Academician I.P. Pavlov

Email: abalenihina88@mail.ru
ORCID iD: 0000-0003-0427-0967
SPIN-code: 4496-9027

Dr.Sc. (Med.), Associate Professor, Professor of the Department of Biological Chemistry Leading Researcher at the Central Research Institute

Russian Federation, Vysokovoltnaya str., 9, Ryazan, 390026

А. V. Shchulkin

Ryazan State Medical University named after Academician I.P. Pavlov

Email: alekseyshulkin@rambler.ru
ORCID iD: 0000-0003-1688-0017
SPIN-code: 2754-1702

Dr.Sc. (Med.), Associate Professor, Professor of the Department of Pharmacology, Leading Researcher at the Central Research Institute

Russian Federation, Vysokovoltnaya str., 9, Ryazan, 390026

P. D. Ananyeva

Ryazan State Medical University named after Academician I.P. Pavlov

Email: erokhina.pelageya96@yandex.ru
ORCID iD: 0000-0003-4802-5656
SPIN-code: 1480-6854

Assistant Professor of the Department of Pharmacology, Researcher at the Central Research Institute

Russian Federation, Vysokovoltnaya str., 9, Ryazan, 390026

М. G. Konopleva

Ryazan State Medical University named after Academician I.P. Pavlov

Email: mari.konopleva.97@mail.ru
ORCID iD: 0000-0002-0813-1430
SPIN-code: 3087-0235

Post-graduate Students, Central Scientific Research Laboratory

Russian Federation, Vysokovoltnaya str., 9, Ryazan, 390026

М. А. Kurganova

Ryazan State Medical University named after Academician I.P. Pavlov

Email: mari.skoblikova.01@inbox.ru
ORCID iD: 0009-0007-7937-0774

Student, Faculty of Medicine 

Russian Federation, Vysokovoltnaya str., 9, Ryazan, 390026

Е. N. Yakusheva

Ryazan State Medical University named after Academician I.P. Pavlov

Email: e.yakusheva@rzgmu.ru
ORCID iD: 0000-0001-6887-4888
SPIN-code: 2865-3080

Dr.Sc. (Med.), Professor, Head of the Department of Pharmacology

Russian Federation, 390026 г. Рязань, ул. Высоковольтная, д. 9

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Supplementary files

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2. Fig. 1. Relative expression of SLCO1B1 mRNA in HepG2 cells exposed to estradiol, progesterone, and testosterone, mean±SD (n=3 in each series)

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3. Fig. 2. Relative expression of SLCO1B3 mRNA in HepG2 cells exposed to estradiol, progesterone, and testosterone, mean±SD (n=3 in each series)

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