ABSTRACT
Covid-19 progression shows sex-dependent features. It is hypothesized that a better Covid-19 survival rate in females can be attributed to the presence of higher 17ß-estradiol (E2) levels in women than in men. Virus SARS-CoV-2 is enabled to enter the cell with the use of angiotensin converting enzyme 2 (ACE2). The expression of several renin-angiotensin system components has been shown to exert a rhythmic pattern, and a role of the circadian system in their regulation has been implicated. Therefore, the aim of the study is to elucidate possible interference between E2 signalling and the circadian system in the regulation of the expression of ACE2 mRNA and functionally related molecules. E2 was administered at a dosage of 40 µg/kg/day for 7 days to male Wistar rats, and sampling of the lungs and colon was performed during a 24-h cycle. The daily pattern of expression of molecules facilitating SARS-CoV-2 entry into the cell, clock genes and E2 receptors was analysed. As a consequence of E2 administration, a rhythm in ACE2 and TMPRSS2 mRNA expression was observed in the lungs but not in the colon. ADAM17 mRNA expression showed a pronounced rhythmic pattern in both tissues that was not influenced by E2 treatment. ESR1 mRNA expression exerted a rhythmic pattern, which was diminished by E2 treatment. The influence of E2 administration on ESR2 and GPER1 mRNA expression was greater in the lungs than in the colon as a significant rhythm in ESR2 and GPER1 mRNA expression appeared only in the lungs after E2 treatment. E2 administration also increased the amplitude of bmal1 expression in the lungs, which implicates altered functioning of peripheral oscillators in response to E2 treatment. The daily pattern of components of the SARS-CoV-2 entrance pathway and their responsiveness to E2 should be considered in the timing of pharmacological therapy for Covid-19.
Subject(s)
ADAM17 Protein , Angiotensin-Converting Enzyme 2 , COVID-19 Drug Treatment , COVID-19 , Colon , Estradiol , Lung , Receptors, Estradiol , ADAM17 Protein/genetics , Angiotensin-Converting Enzyme 2/genetics , Animals , COVID-19/virology , Colon/drug effects , Colon/metabolism , Estradiol/pharmacology , Female , Lung/metabolism , Male , Peptidyl-Dipeptidase A/metabolism , RNA, Messenger/biosynthesis , RNA, Messenger/genetics , Rats , Rats, Wistar , Receptors, Estradiol/genetics , Receptors, Estradiol/metabolism , SARS-CoV-2/physiology , Serine Endopeptidases/genetics , Transcription, Genetic/drug effects , Virus InternalizationABSTRACT
The sleep/wake rhythm is one of the most important biological rhythms. Quality and duration of sleep change during lifetime. The aim of our study was to determine differences in sleep efficiency, movement, and fragmentation during sleep period between genders and according to age. Sleep period was monitored by wrist actigraphy under home-based conditions. Seventy-four healthy participants-47 women and 27 men participated in the study. The participants were divided by age into groups younger than 40 years and 40 years and older. Women showed lower sleep fragmentation and mobility during sleep compared to men. Younger women showed a higher actual sleep and sleep efficiency compared to older women and younger men. Younger men compared to older men had a significantly lower actual sleep, lower sleep efficiency and significantly more sleep and wake bouts. Our results confirmed differences in sleep parameters between genders and according to age. The best sleep quality was detected in young women, but gender differences were not apparent in elderly participants, suggesting the impact of sex hormones on sleep.