Neuroendocrinology
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In this review, we provide a brief summary of several key studies that broaden our understanding of stress and its epigenetic control of the function and behavior of the hypothalamic-pituitary-adrenal (HPA) axis. Clinical and animal studies suggest a link among exposure to stress, dysregulation of the HPA axis, and susceptibility to neuropsychiatric illnesses. Recent studies have supported the notion that exposure to glucocorticoids and stress in various forms, durations, and intensities during different periods of development leads to long-lasting maladaptive HPA axis response in the brain. ⋯ While a definitive role for epigenetic mechanisms remains unclear, these emerging studies implicate glucocorticoid signaling and its ability to alter the epigenetic landscape as one of the key mechanisms that alter the function of the HPA axis and its associated cascades. We also suggest some of the requisite studies and techniques that are important, such as additional candidate gene approaches, genome-wide epigenomic screens, and innovative functional and behavioral studies, in order to further explore and define the relationship between epigenetics and HPA axis biology. Additional studies examining stress-induced epigenetic changes of HPA axis genes, aided by innovative techniques and methodologies, are needed to advance our understanding of this relationship and lead to better preventive, diagnostic, and corrective measures.
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The identification of accurate harbingers of disease status and therapeutic efficacy are critical requirements in precise diagnosis and effective management. Initially, tissue analysis was regarded as ideal but invasive strategies represent risk compared with peripheral blood sampling. Thus far, most biomarkers, whether in tissue or blood/urine, have been single analytes with varying degrees of sensitivity and specificity. ⋯ This overview examines limitations in current practice and describes contemporary viable strategies under evaluation, including the identification of novel analytes (gene transcripts, microRNA), circulating tumor cells and metabolic imaging agents that identify disease. Novel requirements are necessary to develop biomathematical algorithms for synchronous calibration of multiple molecular markers and predictive nomograms that interface biological variables to delineate disease progress or treatment efficacy. Optimally, the application of novel techniques and amalgamations of multianalyte assessment will provide a personalized molecular disease signature extrapolative of neuroendocrine neoplasia status and likelihood of progression and predictive of therapeutic opportunity.
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A pivotal event in the onset of puberty in humans is the reemergence of the pulsatile release of the gonadotropin-releasing hormone (GnRH) from hypothalamic neurons. Pathways governing GnRH ontogeny and physiology have been discovered by studying animal models and humans with reproductive disorders. Recent human studies implicated the activation of kisspeptin and its cognate receptor (KISS1/KISS1R) and the inactivation of MKRN3 in the premature reactivation of GnRH secretion, causing central precocious puberty (CPP). ⋯ The MKRN3 protein is derived only from RNA transcribed from the paternally inherited copy of the gene due to maternal imprinting. Currently, MKRN3 defects represent the most frequent known genetic cause of familial CPP. In this review, we explored the clinical, hormonal and genetic aspects of children with sporadic or familial CPP caused by mutations in the kisspeptin and MKRN3 systems, essential genetic factors for pubertal timing.
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Recent data indicate that there is a link between depression and diabetes and that excess glucocorticoids may play an underlying role in the pathogenesis of both of these diseases. The aim of the present study was to determine whether there are any alterations in glucose, glycogen, glucose transporters, insulin, insulin receptors or corticosterone concentrations in the hippocampus and frontal cortex in a prenatal stress rat model of depression. ⋯ The increase in carbohydrate brain concentrations evoked by prenatal stress may result from changes in the amounts of glucose transporters, especially GLUT1. Moreover, the obtained results support the hypothesis that stress during the perinatal period permanently increases the sensitivity of brain tissue to factors that act in adulthood. © 2014 S. Karger AG, Basel.
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Randomized Controlled Trial
Acute effects of 3,4-methylenedioxymethamphetamine and methylphenidate on circulating steroid levels in healthy subjects.
3,4-Methylenedioxymethamphetamine (MDMA, 'ecstasy') and methylphenidate are widely used psychoactive substances. MDMA primarily enhances serotonergic neurotransmission, and methylphenidate increases dopamine but has no serotonergic effects. Both drugs also increase norepinephrine, resulting in sympathomimetic properties. ⋯ In summary, the serotonin releaser MDMA has acute effects on circulating steroids. These effects are not observed after stimulation of the dopamine and norepinephrine systems with methylphenidate. The present findings support the view that serotonin rather than dopamine and norepinephrine mediates the acute pharmacologically induced stimulation of the hypothalamic-pituitary-adrenal axis in the absence of other stressors.