Physiology of sleep, miRNA, circadian proteins and the assessment of anthropometric, hormonal factors, quality of life and sex among young adults.

head of the study: Wojciech Kuczyński MD, PhD

Planned start of the research: March 2020
Planned ending of the research: March 2022

THE 2D:4D RATIO

The 2D:4D index determines the ratio of the length of the second (2D; index) to the fourth (4D; ring) finger. This is an anthropometric index, which may show sexual dimorphism. The 2D:4D ratio seems to remain unchanged throughout human life. It is recognized that the value of this indicator is determined in early fetal life under the influence of prenatal proportion of the sex hormones. It is a biomarker of balance between prenatal testosterone and prenatal estrogens in the early fetal period. Men have a lower value of this indicator in relation to women (longer ring finger in relation to the index), which is due to the effect of high androgen concentration and low estrogen concentration in the prenatal period. It has been proven that a lower value of this indicator is associated, among others, with increased reproductive success in men, increased aggression and congenital adrenal hyperplasia.

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In women, the value of this indicator is usually higher, which is due to the fact that the fetus in the prenatal period was more affected by estrogens than androgens. Studies have also shown that a higher value of this indicator is associated, among others, with an increased risk of depression in men, obesity, as well as an increased risk of bulimia in women. There is a lack of literature in the literature assessing the relationship between sleep quality and architecture, and the 2D: 4D indicator.

the circadian rhythm

The proper functioning of the body is determined by the circadian rhythm. It depends on the internal clock and regulating numerous physiological processes determines what time of sleep, as well as what time of activity and wakefulness is most beneficial for the human body. Circadian arrhythmias lead to poorer quality of life, increasing the risk of both somatic and mental illness.

The suprachiasmatic nucleus located in the hypothalamus is responsible for the regulation and synchronization of processes conditioned by the circadian rhythm. This structure receives a signal about the current light intensity from the retina through the retinal-hypothalamic pathway. Synchronization of the central biological clock with the rest of the body occurs with the help of melatonin, a hormone secreted by the pineal gland in the dark. Thanks to this, it is possible to coordinate and adapt to the current time of day many physiological processes such as sleep, hormone secretion, metabolism, body temperature, blood pressure, and digestive system work. The existence of a biological clock also allows the time separation of opposing processes such as glycogenolysis and gluconeogenesis.

The molecular mechanism of the biological clock is based on the action of regulatory proteins such as PER, TIM, and CLOCK. These proteins and their genes form the so-called transcriptional-translational feedback loop, which cycle lasts about 24 hours. The synthesis of proteins dependent on the internal clock makes it possible to increase the activity or inhibit many metabolic pathways, whose activity and consequences are beneficial at a given time of day.

The PER protein is encoded by the Period gene. Its synthesis occurs at night and the concentration changes significantly during the 24-hour circadian rhythm. For the oscillatory function of the Period gene, the CLOCK (CLK) and CYCLE (CYC) proteins are required, which in the cytoplasm form heterodimers and in this form pass into the cell nucleus. Then, by attaching to the promoter of the Per gene, they initiate its transcription, and the resulting mRNA is transported to the cytoplasm, where it serves as a matrix for the synthesis of the PER protein. The greatest intensity of this process occurs in the evening. The mechanism of regulating the circadian rhythm also participates in the night-time active Timeless gene, encoding the TIM protein. At night, PER and TIM proteins combine into heterodimers, these complexes accumulate, which allows them to be transported from the cytoplasm to the cell nucleus. After entering the nucleus, the PER-TIM complex begins to inhibit transcription of its own genes and genes activated by CLK and CYC. In this way, the transcription-translational feedback loop is closed.

The biological clock synchronizes the endogenous rhythm with the rhythm of changes in environmental conditions by receiving information about changes in external factors (German Zeitgebers – “time donor”) such as social and mental activity, physical effort, temperature and food, and primarily through reactions to changes in the main factor which there is light. Gene transcription is resumed only when the degradation of PER and TIM proteins occurring during the day can withstand the repression of their own gene expression. This is due to the fact that light stimuli activate the photoreceptor – flavoprotein cryptochrome protein (CRY; CRYPTOCHROME). CRY plays a role in the light-dependent degradation of the TIM protein. Under the influence of light stimuli, CRY and TIM form heterodimers, which leads to phosphorylation, followed by ubiquitination and degradation in the TIM protein proteasomes. As a consequence of the reduced TIM protein concentration, the PER protein concentration is also lowered, which is unstable as a monomer, which leads to its degradation. The transcription of the Per and Tim genes is unblocked and these proteins can be re-synthesized.

Human sleep consists of two types of sleep – REM phase, i.e. the phase of rapid eye movements and nREM, i.e. the phase without rapid eye movements, which occur cyclically. During sleep, blood levels of testosterone increase in men. Overnight production of this hormone reaches its peak during the first 3 hours of undisturbed sleep, usually during the first REM phase. Reduced sleep performance and the number of REM sleep phases are associated with lower circulating testosterone levels. The proper level of testosterone determines proper sexual activity.

Aim of the study

The purpose of this study is to check whether there is a relationship between the biochemical parameters tested (hormone levels: testosterone, estrogen, estradiol, progesterone, luteinizing hormone, follicle-stimulating hormone, prolactin, and melatonin, as well as the level of circadian regulatory proteins – CLOCK, PER and TIM), variables anthropometric (body weight, height, body mass index – BMI, 2D finger length index: 4D, waist and hip circumference index – WHR, thigh, chest, and neck circumference), mental health aspects (depression, hypomanic behavior) and sexual life of students, and the structure of sleep, sleep latency and chronotype, i.e. a tendency to optimal functioning at a specific time of day and night.

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