Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01178 (oxytocin)
 15,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The etiology of autism is complex, and in most cases the underlying pathologic mechanisms are unknown. Autism is a hetereogeneous disorder, diagnosed subjectively on the basis of a large number of criteria. Recent research has investigated genetics, in utero insults and brain function as well as neurochemical and immunological factors. On the basis of family and twin studies, there appears to be a genetic basis for a wide "autistic syndrome." About a quarter of cases of autism are associated with genetic disorders such as fragile X syndrome or with infectious diseases such as congenital rubella. Genetic studies have shown an association between autism markers of brain development such as 3 markers of the c-Harvey-ros oncogene and the homeobox gene EN2. In some cases, autism is associated with insults early in gestation, including thalidomide embryopathy. Autism may arise from abnormal central nervous system functioning, since most autistic patients have indications of brain dysfunction, and about half of them have abnormal electroencephalograms. Similarly, the pattern of evoked response potentials and conduction time is altered in autistic children. There is substantial evidence from neuroimaging studies that dysfunctions in the cerebellum and possibly the temporal lobe and association cortex occur in autistic symptoms. Neurochemical studies have investigated the role of serotonin, epinephrine and norepinephrine, since levels of these neurotransmitters are altered in autism, although other hypotheses implicate overactive brain opioid systems and changes in oxytocin neurotransmission. Autoimmunity may also play a role; antibodies against myelin basic protein are often found in children with autism, who also have increased eosinophil and basophil response to IgE-mediated reactions. In summary, the prevailing view is that autism is caused by a pathophysiologic process arising from the interaction of an early environmental insult and a genetic predisposition.
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PMID:Etiology of infantile autism: a review of recent advances in genetic and neurobiological research. 1021 50

Hypothalamic nuclei, including the anterior periventricular (aPV), paraventricular (PVN), and supraoptic (SON) nuclei strongly express the homeobox gene Orthopedia (Otp) during embryogenesis. Targeted inactivation of Otp in the mouse results in the loss of these nuclei in the homozygous null neonates. The Otp null hypothalamus fails to secrete neuropeptides somatostatin, arginine vasopressin, oxytocin, corticotropin-releasing hormone, and thyrotropin-releasing hormone in an appropriate spatial and temporal fashion, and leads to the death of Otp null pups shortly after birth. Failure to produce these neuropeptide hormones is evident prior to E15.5, indicating a failure in terminal differentiation of the aPV/PVN/SON neurons. Absence of elevated apoptotic activity, but reduced cell proliferation together with the ectopic activation of Six3 expression in the presumptive PVN, indicates a critical role for Otp in terminal differentiation and maturation of these neuroendocrine cell lineages. Otp employs distinct regulatory mechanisms to modulate the expression of specific molecular markers in the developing hypothalamus. At early embryonic stages, expression of Sim2 is immediately downregulated as a result of the absence of Otp, indicating a potential role for Otp as an upstream regulator of Sim2. In contrast, the regulation of Brn4 which is also expressed in the SON and PVN is independent of Otp function. Hence no strong evidence links Otp and Brn4 in the same regulatory pathway. The involvement of Otp and Sim1 in specifying specific hypothalamic neurosecretory cell lineages is shown to operate via distinct signaling pathways that partially overlap with Brn2.
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PMID:The murine Otp homeobox gene plays an essential role in the specification of neuronal cell lineages in the developing hypothalamus. 1107 65

Several behavioral and physiological processes such as social, sexual, and maternal behaviors, learning and memory, and parturition are influenced by the neurohypophysial peptide oxytocin. Studies in knockout mice have identified four transcriptional regulatory genes that are required for oxytocin neuronal development in the hypothalamus. These are the basic helix-loop-helix PAS genes Single-minded 1 (Sim1) and Arylhydrocarbon receptor nuclear translocator 2 (Arnt2), the POU homeobox gene Pou3f2, and the paired homeobox gene Orthopedia (Otp). Overall, however, the molecular control of oxytocin cell development is poorly understood. Studies in zebrafish provide a complementary view to mouse knockout experiments and facilitate understanding of neuroendocrine cell development. Isotocin, which is orthologous to oxytocin, is expressed early in the developing zebrafish brain. In this paper we show that zebrafish otp mRNA expression in the embryonic forebrain is dynamic and complex, and that it overlaps with isotocin expression in the dorsal preoptic area. Additionally, these studies demonstrate that otp is required for isotocin cell development. Evidence is also provided that otp and sim1 function in parallel to direct the differentiation of isotocin cells, and that otp is unlikely to affect brain patterning. Overall, these studies support the hypothesis that the role of otp in zebrafish neuroendocrine cell development is evolutionarily conserved with that of mammals.
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PMID:Zebrafish orthopedia (otp) is required for isotocin cell development. 1718 Jun 84