Hormonal Circadian Rhythms Research Articles

Demographics and Clinical Presentations of Patients Visiting the Emergency Department During the Holy Month of Ramadan: A Three-Year Retrospective Study in a Muslim-Majority Country.

Background and objective Ramadan is the Muslim's holiest month; it is a time when believers engage in special practices that include fasting from dawn till dusk and making cultural and dietary modifications in their everyday lives. The impact of Ramadan on human activity, sleeping patterns, and circadian rhythms of hormones have been addressed in the literature. Fasting, which constitutes the main pillar of practices during Ramadan and lasts from sunrise to sunset, can significantly affect common health conditions, leading many to seek medical care in theEmergency Department (ED). Hence, it is important to understand the pattern of ED visits and understand the impact caused by fasting during this holy monthin a Muslim-majority country. In light of this, this study aimedto gather new insights intothe pattern of ED visits during Ramadan at a busy tertiary care center in the period from 2019 to 2021. Methods This study was conducted by reviewing the hospital health information system to gather relevant information in May 2022. Data of patients who visited the ED during Ramadan were collected, as well asduring a month prior to and after Ramadan for the purpose of comparison. Sociodemographic characteristicsand clinical profiles were collected for analysis. Results The total number of ED visits in thethree months of Ramadan during the study period (three years) was 33,142, all of which were included in our analysis. Sociodemographic data were analyzed for patients who visited the ED during the month of Ramadan and the two lunar months that precede and succeed Ramadan (Shaban and Shawal). Fever was the most common complaint (16.5%), followed by abdominal pain (14%). When analyzing the findings based on patient age groups, fever was found to be the most prevalent complaint in bothadults (15.6%) and pediatric patients (34.4%). Of the total ED patient visits, 7,527 patients were admitted for further care, and197 patientsdeceased. Conclusion Our study findings illustrate the change in ED visit patterns during the month of Ramadan in a Muslim-majority country. Also, the type of complaints was affected significantly due to the ongoing coronavirus disease 2019 (COVID-19) pandemic during the study period. The outcomes in patients reflected substantial progress and outcomesin the ED. These findings highlight that analyzing EDdata can help provide accurate information that can be used to help modify/adjust the quality of services provided in the ED. However, these modificationsmay affect all hospital facilities, not just the ED.

Disturbances of Hormonal Circadian Rhythms by Light Pollution.

The circadian rhythms evolved to anticipate and cope with cyclic changes in environmental conditions. This adaptive function is currently compromised by increasing levels of artificial light at night (ALAN), which can represent a risk for the development of diseases of civilisation. The causal links are not completely understood, and this featured review focuses on the chronodisruption of the neuroendocrine control of physiology and behaviour by dim ALAN. The published data indicate that low levels of ALAN (2-5 lux) can attenuate the molecular mechanisms generating circadian rhythms in the central oscillator, eliminate the rhythmic changes in dominant hormonal signals, such as melatonin, testosterone and vasopressin, and interfere with the circadian rhythm of the dominant glucocorticoid corticosterone in rodents. These changes are associated with a disturbed daily pattern of metabolic changes and behavioural rhythms in activity and food and water intake. The increasing levels of ALAN require the identification of the pathways mediating possible negative consequences on health to design effective mitigation strategies to eliminate or minimise the effects of light pollution.

Benefits, mechanisms, and risks of intermittent fasting in metabolic syndrome and type 2 diabetes.

One of the emergent nutritional strategies for improving multiple features of cardiometabolic diseases is the practice of intermittent fasting (IF), which consists of alternating periods of eating and fasting. IF can reduce circulating glucose and insulin levels, fat mass, and the risk of developing age-related pathologies. IF appears to upregulate evolution-conserved adaptive cellular responses, such as stress-response pathways, autophagy, and mitochondrial function. IF was also observed to modulate the circadian rhythms of hormones like insulin or leptin, among others, which levels change in conditions of food abundance and deficit. However, some contradictory results regarding the duration of the interventions and the anterior metabolic status of the participants suggest that more and longer studies are needed in order to draw conclusions. This review summarizes the current knowledge regarding the role of IF in the modulation of mechanisms involved in type 2 diabetes, as well as the risks.

Effects of Intermittent Fasting on the Circulating Levels and Circadian Rhythms of Hormones.

Intermittent fasting has become an increasingly popular strategy in losing weight and associated reduction in obesity-related medical complications. Overwhelming studies support metabolic improvements from intermittent fasting in blood glucose levels, cardiac and brain function, and other health benefits, in addition to weight loss. However, concerns have also been raised on side effects including muscle loss, ketosis, and electrolyte imbalance. Of particular concern, the effect of intermittent fasting on hormonal circadian rhythms has received little attention. Given the known importance of circadian hormonal changes to normal physiology, potential detrimental effects by dysregulation of hormonal changes deserve careful discussions. In this review, we describe the changes in circadian rhythms of hormones caused by intermittent fasting. We covered major hormones commonly pathophysiologically involved in clinical endocrinology, including insulin, thyroid hormones, and glucocorticoids. Given that intermittent fasting could alter both the level and frequency of hormone secretion, decisions on practicing intermittent fasting should take more considerations on potential detrimental consequences versus beneficial effects pertaining to individual health conditions.

The Night Effect of Anger: Relationship with Nocturnal Blood Pressure Dipping.

Introduction: The circadian pattern of blood pressure is characterized by a physiological drop occurring after sleep onset. The alteration of this phenomenon (non-dipping, extreme dipping, or reverse dipping) is associated with an increased cardiovascular risk. Besides altered autonomic and endocrine circadian rhythms, psychological aspects seem to play a role in this modification. However, the few studies that have analyzed the influence of psychological dimensions on the dipping phenomenon have reported inconsistent results. This study aimed to examine the relationship between anger expression and blood pressure (BP) dipping. Methods: We obtained 24 h ambulatory BP measurements from 151 participants and used them to define three groups according to their dipping status: Dippers (N = 65), Non-Dippers (N = 42), and Extreme Dippers (N = 44). Sociodemographic and anamnestic information was collected, and the State–Trait Anger Expression Inventory was used to assess anger. Results: Analysis of variance evidenced significant higher scores for Trait Anger Temperament and Anger Expression in Extreme Dippers than in both Dippers and Non-Dippers. However, after controlling for confounding variables, there was no significant relationship with trait anger, and only the result concerning the suppression of anger was confirmed. Conclusions: These findings suggest that the analysis of some psychological factors, such as anger, could be necessary to better understand differences in nocturnal BP alterations. Trait anger and suppression of anger may contribute to the description and classification of patients who exhibit a maladaptive dipping phenomenon. However, modifiable (i.e., cigarette consumption) and unmodifiable (i.e., age) risk factors appear to mediate this relationship. Although further studies are necessary to explore this association, these results highlight that some aspects of anger can represent risk factors or markers of maladaptive modulation of the dipping phenomenon.

Pediatric cyclical Cushing’s disease: a case report and literature review

The article presents a rare clinical case of cyclical Cushing’s disease in a child. A 9‑year‑old boy complained of excessive weight gain for 3 years. Obesity had been progressing for the following 2 years, and then the child lost 14 kg in 5 months. Growth hormone deficiency with regard to slow growth rate and hypogonadism due to maintaining of prepubertal gonadal size were excluded. Taking into account the history of obesity and low growth rate, the child was repeatedly examined for hypercortisolism. The urinary 24‑h cortisol excretion and the overnight dexamethasone suppression test didn’t confirm hypercortisolism in spite of detected impairment of the adrenocorticotropic hormone circadian rhythm. Resumption of weight gain was observed at the age of 13.5 years. The results of urinary 24‑h cortisol excretion confirmed hypercortisolism. Magnetic resonance imaging of pituitary was unremarkable. The boy underwent simultaneous bilateral selective blood sampling from the cavernous, inferior petrosal, and sigmoid sinuses. Significant positive adrenocorticotropic hormone gradient was registered in the left cavernous sinus compared to peripheral levels, so Cushing’s disease was diagnosed. Endoscopic transnasal surgery was conducted and abnormal tissue was resected. Histopathology revealed no pituitary adenoma. The article provides a brief review on the cyclic Cushing’s disease in children and the main reasons of negative results of histopathology.

Sex differences in circadian endocrine rhythms: Clinical implications.

Organisms have developed a highly conserved and tightly regulated circadian system, to adjust their daily activities to day/night cycles. This system consists of a central clock, which is located in the hypothalamic suprachiasmatic nucleus, and the peripheral clocks that are ubiquitously expressed in all tissues. Both the central and peripheral clocks communicate with each other and achieve circadian oscillations of gene expression through transcriptional/translational loops mediated by clock transcription factors. It is worth mentioning that circadian non-transcriptional/non-translational rhythms also occur in non-nucleated cells. Interestingly, sex has been identified as an important factor influencing the activity of the circadian system. Indeed, several sex differences have been documented in the anatomy, physiology and pathophysiology that pertain to circadian rhythms. In this review, we present the historical milestones of understanding circadian rhythms, describe the central and peripheral components of the circadian clock system, discuss representative examples of sexual dimorphism of circadian rhythms, and present the most relevant clinical implications.

P.419 Beneficial role of endurance training on desynchronized hormonal circadian rhythms in experimental model of melatonin deficit

P.419 Beneficial role of endurance training on desynchronized hormonal circadian rhythms in experimental model of melatonin deficit

Energy Metabolism and Intermittent Fasting: The Ramadan Perspective.

Intermittent fasting (IF) has been gaining popularity as a means of losing weight. The Ramadan fast (RF) is a form of IF practiced by millions of adult Muslims globally for a whole lunar month every year. It entails a major shift from normal eating patterns to exclusive nocturnal eating. RF is a state of intermittent liver glycogen depletion and repletion. The earlier (morning) part of the fasting day is marked by dominance of carbohydrate as the main fuel, but lipid becomes more important towards the afternoon and as the time for breaking the fast at sunset (iftar) gets closer. The practice of observing Ramadan fasting is accompanied by changes in sleeping and activity patterns, as well as circadian rhythms of hormones including cortisol, insulin, leptin, ghrelin, growth hormone, prolactin, sex hormones, and adiponectin. Few studies have investigated energy expenditure in the context of RF including resting metabolic rate (RMR) and total energy expenditure (TEE) and found no significant changes with RF. Changes in activity and sleeping patterns however do occur and are different from non-Ramadan days. Weight changes in the context of Ramadan fast are variable and typically modest with wise inter-individual variation. As well as its direct relevance to many religious observers, understanding intermittent fasting may have implications on weight loss strategies with even broader potential implications. This review examines current knowledge on different aspects of energy balance in RF, as a common model to learn from and also map out strategies for healthier outcomes in such settings.

Testosterone-mediated activation of androgenic signalling sustains in vitro the transformed and radioresistant phenotype of rhabdomyosarcoma cell lines.

Rhabdomyosarcoma (RMS), the most common soft-tissue sarcoma in childhood, rarely affects adults, preferring male. RMS expresses the receptor for androgen (AR) and responds to androgen; however, the molecular action of androgens on RMS is unknown. Herein, testosterone (T) effects were tested in embryonal (ERMS) and alveolar (ARMS) RMS cell lines, by performing luciferase reporter assay, RT-PCR, and western blotting experiments. RNA interference experiments or bicalutamide treatment was performed to assess the specific role of AR. Radiation treatment was delivered to characterise the effects of T treatment on RMS intrinsic radioresistance. Our study showed that RMS cells respond to sub-physiological levels of T stimulation, finally promoting AR-dependent genomic and non-genomic effects, such as the transcriptional regulation of several oncogenes, the phosphorylation-mediated post-transductional modifications of AR and the activation of ERK, p38 and AKT signal transduction pathway mediators that, by physically complexing or not with AR, participate in regulating its transcriptional activity and the expression of T-targeted genes. T chronic daily treatment, performed as for the hormone circadian rhythm, did not significantly affect RMS cell growth, but improved RMS clonogenic and radioresistant potential and increased AR mRNA both in ERMS and ARMS. AR protein accumulation was evident in ERMS, this further developing an intrinsic T-independent AR activity. Our results suggest that androgens sustain and improve RMS transformed and radioresistant phenotype, and therefore, their therapeutic application should be avoided in RMS post puberal patients.

Relationship Between the Cortisol-Estradiol Phase Difference and Affect in Women.

Affective disorders impact women’s health, with a lifetime prevalence of over twelve per cent. They have been correlated with reproductive cycle factors, under the regulation of hormonal circadian rhythms. In affective disorders, circadian rhythms may become desynchronized. The circadian rhythms of cortisol and estradiol may play a role in affective disorders. The purpose of this study was to explore the temporal relationship between the rhythms of cortisol and estradiol and its relationship to affect. It was hypothesized that a cortisol-estradiol phase difference (PD) exists that correlates with optimal affect. A small scale, comparative, correlational design was used to test the hypothesis. Twenty-three women were recruited from an urban university. Salivary samples were collected over a twenty-four-hour period and fitted to a cosinor model. Subjective measures of affect were collected. Relationships between the cortisol-estradiol PD and affect were evaluated using a second-degree polynomial equation. Results demonstrated a significant correlation in affect measures (p < 0.05). An optimal PD was identified for affect to be 3.6 hours. The phase relationship between cortisol and estradiol may play a role in the development of alterations in affective disorders.

Fitting tissue chips and microphysiological systems into the grand scheme of medicine, biology, pharmacology, and toxicology.

Microphysiological systems (MPS), which include engineered organoids (EOs), single organ/tissue chips (TCs), and multiple organs interconnected to create miniature in vitro models of human physiological systems, are rapidly becoming effective tools for drug development and the mechanistic understanding of tissue physiology and pathophysiology. The second MPS thematic issue of Experimental Biology and Medicine comprises 15 articles by scientists and engineers from the National Institutes of Health, the IQ Consortium, the Food and Drug Administration, and Environmental Protection Agency, an MPS company, and academia. Topics include the progress, challenges, and future of organs-on-chips, dissemination of TCs into Pharma, children's health protection, liver zonation, liver chips and their coupling to interconnected systems, gastrointestinal MPS, maturation of immature cardiomyocytes in a heart-on-a-chip, coculture of multiple cell types in a human skin construct, use of synthetic hydrogels to create EOs that form neural tissue models, the blood-brain barrier-on-a-chip, MPS models of coupled female reproductive organs, coupling MPS devices to create a body-on-a-chip, and the use of a microformulator to recapitulate endocrine circadian rhythms. While MPS hardware has been relatively stable since the last MPS thematic issue, there have been significant advances in cell sourcing, with increased reliance on human-induced pluripotent stem cells, and in characterization of the genetic and functional cell state in MPS bioreactors. There is growing appreciation of the need to minimize perfusate-to-cell-volume ratios and respect physiological scaling of coupled TCs. Questions asked by drug developers are followed by an analysis of the potential value, costs, and needs of Pharma. Of highest value and lowest switching costs may be the development of MPS disease models to aid in the discovery of disease mechanisms; novel compounds including probes, leads, and clinical candidates; and mechanism of action of drug candidates. Impact statement Microphysiological systems (MPS), which include engineered organoids and both individual and coupled organs-on-chips and tissue chips, are a rapidly growing topic of research that addresses the known limitations of conventional cellular monoculture on flat plastic - a well-perfected set of techniques that produces reliable, statistically significant results that may not adequately represent human biology and disease. As reviewed in this article and the others in this thematic issue, MPS research has made notable progress in the past three years in both cell sourcing and characterization. As the field matures, currently identified challenges are being addressed, and new ones are being recognized. Building upon investments by the Defense Advanced Research Projects Agency, National Institutes of Health, Food and Drug Administration, Defense Threat Reduction Agency, and Environmental Protection Agency of more than $200 million since 2012 and sizable corporate spending, academic and commercial players in the MPS community are demonstrating their ability to meet the translational challenges required to apply MPS technologies to accelerate drug development and advance toxicology.

The importance of hormonal circadian rhythms in daily feeding patterns: An illustration with simulated pigs

The interaction between hormonal circadian rhythms and feeding behaviour is not well understood. This study aimed to deepen our understanding of mechanisms underlying circadian feeding behaviour in animals, using pigs, Sus scrofa, as a case study. Pigs show an alternans feeding pattern, that is, a small peak of feed intake at the beginning of the day and a larger peak at the end of the day. We simulated the feeding behaviour of pigs over a 24h period. The simulation model contained mechanisms that regulate feeding behaviour of animals, including: processing of feed in the gastrointestinal tract, fluctuation in energy balance, circadian rhythms of melatonin and cortisol and motivational decision-making. From the interactions between these various processes, feeding patterns (e.g. feed intake, meal frequency, feeding rate) emerge. These feeding patterns, as well as patterns for the underlying mechanisms (e.g. energy expenditure), fitted empirical data well, indicating that our model contains relevant mechanisms. The circadian rhythms of cortisol and melatonin explained the alternans pattern of feeding in pigs. Additionally, the timing and amplitude of cortisol peaks affected the diurnal and nocturnal peaks in feed intake. Furthermore, our results suggest that circadian rhythms of other hormones, such as leptin and ghrelin, are less important in circadian regulation of feeding behaviour than previously thought. These results are relevant to animal species with a metabolic and endocrine system similar to that of pigs, such as humans. Moreover, the modelling approach to understand feeding behaviour can be applied to other animal species.

Dissociation of Molecular and Endocrine Circadian Rhythms in Male Mice Lacking Bmal1 in the Adrenal Cortex.

The circadian rhythm of glucocorticoids affects diverse physiological systems, including stress responses and the coordination of rhythmic functions in peripheral and central tissues. Circadian clocks are considered to be important coordinators of glucocorticoid release and loss of the core clock component Brain and muscle Arnt-like protein-1 leads to ablation of behavioral and physiological rhythms, hypocortisolism, impaired ACTH, and behavioral stress responses. Transplantation and conditional clock gene knock-down studies in mice suggest an important role of local adrenocortical clock function in this context. Here, we present a Cre-loxP-mediated conditional knockout of Bmal1 in the steroidogenic cells of the adrenal cortex in mice. Mutant animals show a loss of molecular clock gene activity rhythms in this tissue with subsequent disruption of rhythmic steroidogenic gene expression. However, despite this loss of normal clock rhythmicity in the adrenal cortex, behavioral and physiological rhythms and acute stress responses persist in mutant mice. These findings reveal a dissociation of transcriptional and endocrine rhythm regulation in the adrenal cortex, arguing for a less pivotal function of the local clock machinery in the regulation of circadian and acute glucocorticoid outputs.

Evolutionary Endocrinology of Hormonal Rhythms: Juvenile Hormone Titer Circadian Polymorphism in Gryllus firmus.

Daily rhythms for hormonal traits are likely widespread and important aspects of organismal (e.g., life history) adaptation. Yet they remain substantially understudied, especially with respect to variable rhythms within species. The cricket, Gryllus firmus, exhibits a genetically polymorphic circadian rhythm for the blood titer of the key hormone, juvenile hormone (JH). Gryllus firmus is also wing-polymorphic, consisting of a dispersing morph that delays reproduction and a flightless morph with substantially enhanced egg production. JH circadian phenotype strongly covaries with morph type: The blood JH titer is strongly rhythmic in multiple populations artificially-selected for the dispersing morph (LW(f) = long wings with functional flight muscles) and is essentially arrhythmic in populations selected for the SW (short-winged) morph. Association between JH titer cycle and LW(f) morph is also found in natural populations of G. firmus and in several related species in the field. This is one of the very few studies of endocrine titer variation in natural populations of an insect. The morph-specific cycle is underlain by a circadian rhythm in hormone biosynthesis, which in turn is underlain by a rhythm in a brain neuropeptide regulator of JH biosynthesis. The morph-specific JH titer circadian cycle is also strongly correlated with a morph-specific daily rhythm in global gene expression. This is currently the only example of a genetically-variable hormone circadian rhythm in both the laboratory and field that is strongly associated with an ecologically important polymorphism. The extensive information on the underlying causes of the morph-specific JH titer rhythm, coupled with the strong association between the JH circadian rhythm and wing polymorphism makes this system in G. firmus an exceptional experimental model to investigate the mechanisms underlying circadian hormonal adaptations. Genetic polymorphism for the JH titer circadian rhythm in G. firmus is discussed in context of circadian rhythms for endocrine traits reported for vertebrates and insects. Consequences of the failure to identify endocrine circadian rhythms on the accuracy of estimation of quantitative-genetic parameters, such as heritability and correlations between hormonal and fitness-related traits, are also discussed.

The pituitary-gonadal-thyroid and lactotroph axes in critically ill patients.

The normal circadian rhythm of hormones in critical patients becomes chaotic causing some hormones to increase and others to decrease abnormally. The goal of this study is to evaluate hormonal changes in severely ill patients and to investigate the relationship between hormonal changes and mortality and morbidity. We enrolled 20 patients (10 F/10 M). Blood samples were collected on day 0, day 5, and day 10. If a patient was discharged before these defined days, a sample was drawn on that day. Twenty healthy controls were included. Female patients had lower LH, FSH, and fT₃ and higher PRL and cortisol levels than controls on admission to the intensive care unit (ICU) (pLH = 0.021, pFSH:0.001, pfT3 = 0.021, pPRL = 0.042, pCortisol <0.001, respectively). Men had significantly low testosterone and fT3, and high PRL and cortisol levels on ICU admission (pT = 0.01, pfT3 = 0.043, pPRL = 0.005, pCortisol < 0.001, respectively). The lowest levels of gonadotropins in both genders and testosterone in men were measured on day 5. Cortisol levels decreased in the patients discharged from the ICU (p = 0.01). FSH levels increased in recovered women (pFSH = 0.043). The mortality rate was 30%. There were correlations between admission TSH and NIMV duration (p = 0.006), fT3 and APACHE II (p = 0.001), and PRL and mortality (p = 0.044). Positive correlations between E2 and APACHE II (p = 0.003) in females, and PRL and APACHE II (p = 0.022) in males were also displayed. Critically ill patients develop significant changes in neuroendocrine axes. Alterations in hormones correlate with the disease severity and mortality. (Endokrynol Pol 2016; 67 (3): 305-312).

Hormonal circadian rhythms in patients with congenital adrenal hyperplasia: identifying optimal monitoring times and novel disease biomarkers.

The treatment goal in congenital adrenal hyperplasia (CAH) is to replace glucocorticoids while avoiding androgen excess and iatrogenic Cushing's syndrome. However, there is no consensus on how to monitor disease control. Our main objectives were to evaluate hormonal circadian rhythms and use these profiles to identify optimal monitoring times and novel disease biomarkers in CAH adults on intermediate- and long-acting glucocorticoids. This was an observational, cross-sectional study at the National Institutes of Health Clinical Center in 16 patients with classic CAH. Twenty-four-hour serum sampling for ACTH, 17-hydroxyprogesterone (17OHP), androstenedione (A4), androsterone, DHEA, testosterone, progesterone and 24-h urinary pdiol and 5β-pdiol was carried out. Bayesian spectral analysis and cosinor analysis were performed to detect circadian rhythmicity. The number of hours to minimal (TminAC) and maximal (TmaxAC) adrenocortical hormone levels after dose administration was calculated. A significant rhythm was confirmed for ACTH (r(2), 0.95; P<0.001), 17OHP (r(2), 0.70; P=0.003), androstenedione (r(2), 0.47; P=0.043), androsterone (r(2), 0.80; P<0.001), testosterone (r(2), 0.47; P=0.042) and progesterone (r(2), 0.64; P=0.006). The mean (s.d.) TminAC and TmaxAC for 17OHP and A4 were: morning prednisone (4.3 (2.3) and 9.7 (3.5) h), evening prednisone (4.5 (2.0) and 10.3 (2.4) h), and daily dexamethasone (9.2 (3.5) and 16.4 (7.2) h). AUC0-24 h progesterone, androsterone and 24-h urine pdiol were significantly related to 17OHP. In CAH patients, adrenal androgens exhibit circadian rhythms influenced by glucocorticoid replacement. Measurement of adrenocortical hormones and interpretation of results should take into account the type of glucocorticoid and time of dose administration. Progesterone and backdoor metabolites may provide alternative disease biomarkers.

Continuous Positive Airway Pressure Treatment Increases Serum Vitamin D Levels in Male Patients with Obstructive Sleep Apnea.

Recent studies report a link between obstructive sleep apnea (OSA) syndrome, low vitamin D levels, and high parathyroid hormone (PTH) concentrations. The aim of the current study is to evaluate the effect of 7-night continuous positive airway pressure (CPAP) therapy on serum vitamin D, PTH, and calcium levels in patients with severe OSA syndrome. Patients with severe OSA were enrolled into the study and compared to control subjects. Patients with OSA underwent CPAP therapy for 7 nights and were consequently divided into responders (OSA-R, mean residual AHI < 5/h) and nonresponders (OSA-nR, mean residual AHI > 5/h). Serum vitamin D, PTH, and calcium levels were measured at baseline in patients with severe OSA (apnea-hypopnea index > 30/h) and control subjects. Patients with OSA underwent a final morning blood sample after 7-night CPAP therapy. We enrolled 90 patients with OSA into the study (65 OSA-R and 25 OSA-nR) compared to 32 control subjects. At baseline, lower vitamin D and higher PTH levels were detected in the OSA group compared to controls. After 7-night CPAP therapy, male OSA-R patients showed a significant increase in vitamin D levels. Conversely, female OSA-R patients did not show the same increase in vitamin D levels. It was also observed that OSA-nR subjects did not show modifications of serum markers after nCPAP-therapy. The study demonstrates that short-term nCPAP treatment is able to promote the recovery of vitamin D homeostasis in male patients with OSA. The mediation of sexual hormones in regulating vitamin D is a possible explanation of the lack of recovery of vitamin D homeostasis in female patients with OSA as it often affects postmenopausal women.

Physiological evidence of an inverse correlation between the gonadal function and rfrp-3 neurons in mice

The temporal phase relation of circadian neural oscillations (serotonergic and dopaminergic) are reported to account for seasonal physiological conditions including reproduction. The circadian rhythms of hormones (corticosterone and prolactin) appear to be important expression of these oscillations and by feed-back mechanism hormonal rhythms may not only maintain the neural oscillations (serotonergic and dopaminergic) but may also entrain each other. Further, in this direction and on the assumption/evidence that hormonal rhythms are the expression of neural rhythms, 5-hydroxytryptophan (5-HTP), a rate limiting precursor substrate for serotonin, was substituted for corticosterone, and L-dihydroxyphenyalanine (L-DOPA), a rate-limiting precursor for dopamine, was substituted for prolactin. Although so far most of the studies have concentrated on the serotonergic and dopaminergic oscillations possibly due to their central effect, role of other oscillations cannot be ruled out. Our study presented in this communication deals with the temporal phase relation between two neural oscillations (serotonergic and dopaminergic) that are conveyed to regulate seasonal reproductive and other metabolic/physiological conditions. Our work tested the applicability of this mechanism in continuous breeder Parkes (P) strain mice during postnatal gonadal development and attainment of puberty with respect to the expression of a hypothalamic gonadotropin-inhibitory peptide, RFamide-related peptide-3 (RFRP-3). Further, age-dependent variations were also monitored in the expression of ir- RFRP-3 in mice brain and the testicular activity to assess the possible correlation between the gonadal function (development, maturation and regression).

Circadian endocrine rhythms: the hypothalamic-pituitary-adrenal axis and its actions.

The stress system effectively restores the internal balance--or homeostasis--of living organisms in the face of random external or internal changes, the stressors. This highly complex system helps organisms to provide a series of neuroendocrine responses to stressors--the stress response--through coordinated activation of the hypothalamic-pituitary-adrenal (HPA) axis and the locus coeruleus/norepinephrine autonomic nervous systems. In addition to stressors, life is influenced by daily light/dark changes due to the 24-h rotation of Earth. To adjust to these recurrent day/night cycles, the biological clock system employs the heterodimer of transcription factors circadian locomotor output cycle kaput/brain-muscle-arnt-like protein 1 (CLOCK/BMAL1), along with a set of other transcription factors, to regulate the circadian pattern of gene expression. Interestingly, the stress system, through the HPA axis, communicates with the clock system; therefore, any uncoupling or dysregulation could potentially cause several disorders, such as metabolic, autoimmune, and mood disorders. In this review, we discuss the biological function of the two systems, their interactions, and the clinical implications of their dysregulation or uncoupling.