Effect of Sex Hormones on Levels of mRNAs Coding for Proteins Involved in Lipid Metabolism in Macrophages

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T. A. Shchelkunova^1*, I. A. Morozov², P. M. Rubtsov^2,3, L. M. Samokhodskaya⁴, I. V. Andrianova^5,6, E. G. Rudimov⁶, I. A. Sobenin⁷, A. N. Orekhov⁷, and A. N. Smirnov^1#

¹Lomonosov Moscow State University, Biological Faculty, Leninskie Gory 1, 119899 Moscow, Russia; fax: (495) 939-4309; E-mail: schelkunova-t@mail.ru

²Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, ul. Vavilova 32, 119991 Moscow, Russia; fax: (499) 135-1405; E-mail: rubtsov@eimb.ru

³Moscow Institute of Physics and Technology, Institutskii Pereulok 9, 141700 Dolgoprudny, Moscow Region, Russia; fax: (495) 576-0813

⁴Lomonosov Moscow State University, Faculty of Fundamental Medicine, Lomonosovsky pr. 31/5, 119899 Moscow, Russia; fax: (495) 932-9904; E-mail: slm@fbm.msu.ru

⁵Russian Cardiological Scientific Production Complex, ul. 3-ya Cherepkovskaya 15A, 121552 Moscow, Russia; fax: (495) 414-6731; E-mail: irandrianova@yandex.ru

⁶Institute of Biomedical Problems, Russian Academy of Sciences, Khoroshevskoe Shosse 76a, 123007 Moscow, Russia; fax: (499) 195-1500

⁷Institute of General Pathology and Pathophysiology, Russian Academy of Medical Sciences, ul. Baltiiskaya 8, 125315 Moscow, Russia; fax: (495) 415-9594; E-mail: office@inat.ru

^* To whom correspondence should be addressed.

^# Deceased.

Received July 15, 2013; Revision received August 30, 2013

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The effects of sex hormones estradiol (E2), testosterone (Te), and 5α-dihydrotestosterone (DT) on cholesterol accumulation induced by modified low density lipoproteins (LDL) in macrophages differentiated from human peripheral blood monocytes and on the levels of mRNAs coding for proteins involved in lipid metabolism have been studied. All three hormones at physiological concentrations (1 nM) are capable of reducing cholesterol accumulation in cells. The treatment of cells with modified and native (not inducing cholesterol accumulation) LDL results in similar alterations in the expression of several mRNAs aimed primarily at homeostatic regulation of lipid metabolism. These alterations depend on the sex of macrophage donors and in some cases are even reversed in cells obtained from male and female donors. The cells not treated with modified LDL have no significant gender differences in the expression of the examined mRNAs. Hormones, either independently or in combination with the modified LDL, influence the levels of some mRNAs, and each hormone shows an individual range of effects. Correlation analysis of changes in mRNA content in the cells showed that the hormones may interfere with coordination of gene expression. Hormone action leads to: (1) reduced coupling of the content of individual mRNAs with their initial levels in the control cells; (2) reduced coupling of different mRNA levels; (3) regrouping of mRNAs between the clusters; and (4) changes in the number of factors that determine the correlation links between mRNAs. The data show that sex hormones may have impact on the level of expression of certain genes and, in particular, on the coordination of gene expression in macrophages.

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KEY WORDS: sex hormones, PCR, gene expression, atherogenesis, macrophages, correlation analysis

DOI: 10.1134/S0006297913120043

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