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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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.