In addition, classical markers to study circadian rhythms in chronobiology research are measured: cortisol and components of the molecular biological clock i.e. The aim of the present study was to investigate diurnal variation of a set of markers (relevant for metabolic disorders and hormone-associated cancers) in a routine setting in males and females, resembling molecular epidemiology studies: namely, non-fasted and limited control for other environmental influences. Therefore, most molecular epidemiology studies collect blood samples to study biomarkers for adverse health outcomes without standardization for time-point, food intake or sleep. Due to the large-scale set up of some molecular epidemiology studies, the possibility for standardization of sample collection to time of day and food consumption is limited. Most information on diurnal variation is derived from these controlled laboratory studies in which factors influencing diurnal variation (such as food intake and/or sleep/wake cycle) are controlled (for example see references ). The diurnal variation of various blood markers has previously been studied in different settings, ranging from a relatively uncontrolled routine setting to very tightly controlled laboratory settings. In this study, we determine whether a set of biomarkers relevant for metabolic disorders and hormone-associated cancers, consisting of endocrine and sex hormones and lipids, shows diurnal variation. When the diurnal variation is larger than the inter-individual variation, time of day should be taken into account in molecular epidemiology studies. This might render accurate determination of markers in molecular epidemiology studies challenging. For example, previous studies have indicated that there are substantial changes in the blood transcriptome after experiencing insufficient or mistimed sleep. Importantly, heterogeneity in diurnal variation and disturbance of circadian rhythms among a study population might increasingly occur as a result of our increasing 24/7 economy and related variation in exposure to environmental factors (such as light and food). Several markers are well known for their diurnal variation, for example cortisol and melatonin. However, environmental factors, such as light exposure and food intake might affect the levels of these markers, since they provide input for the internal time-keeping system. In general, for these markers sampling can occur at any time-point during the day or after an overnight fast. Metabolic markers might serve as important (early) indicators for metabolic disorders, including cardiovascular diseases and type 2 diabetes, and hormonal disbalance is often studied in large epidemiological settings since these are associated with high incidence cancers, such as breast cancer. The precise role of pulsatile TSH secretion in the generation of T4 levels is unclear as disruption of the pulsatile pattern did not affect serum T4 concentration.Many molecular epidemiology studies focusing on high prevalent diseases, such as metabolic disorders and cancer, make use of metabolic and hormonal markers (for examples see references. These data demonstrate pulsatility of serum TSH concentrations in children and confirm previous observations that somatostatin inhibits TSH secretion. Despite these changes serum T4 concentrations remained unchanged during treatment. Treatment with the somatostatin analogue led to a suppression of the nocturnal rise in serum TSH concentration, to a disruption of the dominant periodicities so that no clearly defined pulse frequency could be discerned and to a 30%-50% reduction in 24 hr mean: serum TSH concentration (0.7-1.2 mU/l, median 1.0 mU/l). No change in mean serum 24hr TSH concentrations with age was observed (0.7-5.10 mU/l, median 2.1 mU/l). Two pulse periodicities were observed: a fast frequency of 120 minutes and a slower one of 280 minutes. Nocturnal values were often greater than the upper limit of normal for a random sample (5 mU/l). In short and tall children a circadian variation in serum TSH concentrations was observed with nocturnal values greater than diurnal. We have analysed 24 hr serum TSH concentration profiles in 29 short normal prepubertal subjects and in 9 tall children before and during one year of treatment with a nocturnal infusion of a somatostatin analogue (50-100 mg infused subcutaneously for 12 hrs). TSH has been shown to be secreted in a pulsatile manner in adults.
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