Effect of 17β-estradiol on the daily pattern of ACE2, ADAM17, TMPRSS2 and estradiol receptor transcription in the lungs and colon of male rats.

In the lungs, there was a mild trend toward increased ACE2 mRNA expression at the end of the dark phase of the LD cycle in E2-treated rats compared to the control (t-test, P = 0.145).

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Cosinor analysis revealed a highly significant rhythmic pattern in PER2 mRNA expression in the lungs and colon that reached maximal levels at the beginning of dark phase of the LD cycle in the control (Cosinor, S2 Table ).

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It seems that under some circumstances, ACE2 mRNA expression can exert tissue- and/or species-specific rhythmic pattern; however, the amplitude of this rhythm is always very low or shows borderline significance.

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We observed a pronounced trend to increase in ESR1 mRNA expression at the beginning of light phase in the lungs of E2 treated rats compared to control (t-test, Fig 2A , S2 Table ).

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