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 neurophysins are the carriers of oxytocin and antidiuretic hormone (ADH) along the hypothalamo-neurohypophyseal tract. They are liberated when the hormones are released; their radioimmunoassay which are methodologically more simple than that of the active nonapeptides can be used in clinical practice. Moreover, the separate assay of each major neurophysins bring a specific index of the release of each hormone. The radioimmunoassay for circulating neurophysins appears to be useful for the differential diagnosis of polyuria, water retention and hypothalamic disease. The neurophysins are however devoided of any antidiuretic or oxytocic properties and their half-lives differ slightly from that of circulating hormones: therefore a basal level or values obtained in the course of an inhibitory test must be cautiously interpreted.
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PMID:[The neurophysins (author's transl)]. 73 18

Familial neurohypophyseal diabetes insipidus in humans is a rare disease transmitted as an autosomal dominant trait. Affected individuals have very low or undetectable levels of circulating vasopressin and suffer from polydipsia and polyuria. An obvious candidate gene for the disease is the vasopressin-neurophysin (AVP-NP) precursor gene on human chromosome 20. The 2 kb gene with three exons encodes a composite precursor protein consisting of the neuropeptide vasopressin and two associated proteins, neurophysin and a glycopeptide. Cloning and nucleotide sequence analysis of both alleles of the AVP-NP gene present in a Dutch ADNDI family reveals a point mutation in one allele of the affected family members. Comparison of the nucleotide sequences shows a G----T transversion within the neurophysin-encoding exon B. This missense mutation converts a highly conserved glycine (Gly17 of neurophysin) to a valine residue. RFLP analysis of six related family members indicates cosegregation of the mutant allele with the DI phenotype. The mutation is not present in 96 chromosomes of an unrelated control group. These data suggest that a single amino acid exchange within a highly conserved domain of the human vasopressin-associated neurophysin is the primary cause of one form of ADNDI.
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PMID:A missense mutation in the vasopressin-neurophysin precursor gene cosegregates with human autosomal dominant neurohypophyseal diabetes insipidus. 174 Jan 4

The effects of streptozotocin-induced diabetes on weight gain, bone growth and GH secretion have been studied in conscious chronically cannulated male rats. In addition to the classic diabetic symptoms (hyperphagia, polydipsia, polyuria, glycosuria and hyperglycaemia), the slow body weight gain (0.95 +/- 0.5 compared with 2.63 +/- 0.5 g/day in non-diabetic controls) was associated with a reduction in bone growth (from 162 +/- 9 to 48 +/- 4 microns/day) and a reduced pituitary GH content (from 1.5 +/- 0.2 to 0.6 +/- 0.06 mg/gland). Serial blood sampling during the day or overnight showed that the normal male episodic GH secretory pattern was obliterated in the diabetic animals. The constant osmotic stimulation of hyperglycaemia and high fluid turnover was reflected in a significant reduction in pituitary oxytocin and arginine vasopressin (AVP) stores. Intravenous insulin infusions (67-1340 pmol/h for 4 or 7 days) caused a large initial weight gain (greater than 20 g in 2 days) followed by a slower increase, and stimulated tibial bone growth (to 100 +/- 16 and 126 +/- 8 microns/day after 4 or 7 days respectively). Insulin infusion for 7 days also increased pituitary GH content (to 1 +/- 0.15 mg/gland), and the normal episodic GH secretory pattern returned. Intravenous infusions of insulin which reduced, but did not completely normalize, blood glucose levels, allowed the resumption of growth and pulsatile GH secretion. Continuous infusion of recombinant human insulin-like growth factor-I (hIGF-I) at 1110 pmol/h for 54 h also caused a large initial rise in body weight in diabetic rats (17.1 +/- 1.6 compared with 7.5 +/- 2.8 g in saline-infused controls) due primarily to increased fluid retention. This effect of hIGF-I occurred without any significant changes in pituitary GH, AVP, oxytocin, blood glucose or bone growth over this short-term infusion, nor was there any obvious effect on spontaneous GH secretion, monitored over the entire infusion period. We conclude that the diabetic rat is not a good model to study growth stimulation by short-term insulin or IGF-I treatments because the insulin-like effects of these peptides obscure their specific growth-promoting activities in this model.
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PMID:Growth hormone and growth in diabetic rats: effects of insulin and insulin-like growth factor-I infusions. 268

There is considerable disagreement in the literature on changes in the hypothalamo-neurohypophyseal system (HNS) with aging: some reports support HNS degeneration, whereas others claim an activation of this system in senescence. In order to study age-related changes in vasopressin (VP) and oxytocin (OT) excretion in relation to water metabolism, six young (4 months) and 12 aged (34 months) male Brown-Norway rats were placed in metabolism cages. Since plasma testosterone levels have been reported to affect HNS activity and to decline progressively with age, half of the aged animals were given subcutaneous testosterone implants. Urine volume and water intake were significantly increased in aged animals, while urine osmolality was significantly reduced. These changes could not be attributed to diminished VP secretion, since 24-h urinary excretion of this peptide was elevated in the aged animals. In addition, 24-h OT excretion was elevated in the aged animals, indicating an overall activation of the HNS in senescence. VP excretion was significantly correlated with urine osmolality, urine volume and urinary VP concentration. No significant differences were observed between testosterone- and sham-implanted aged rats. It is concluded that the moderate polyuria/polydipsia in the senescent Brown-Norway rat is probably due to renal changes and is accompanied by a compensatory rise in both VP and OT secretion. Testosterone does not affect these changes.
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PMID:Vasopressin and oxytocin excretion in the Brown-Norway rat in relation to aging, water metabolism and testosterone. 321 21

Previously it was found that grafts of supraoptic plus paraventricular areas from 19-day-old foetal normal rats survived in the third ventricle of the brain of 4- to 6-day-old, vasopressin-deficient Brattleboro pups, but could not alleviate their polyuria. In the present series, factors important in graft development were analysed. Again using day-19 fetuses as donors, anterohypothalamus grafts as well as grafts placed near a crushed median eminence survived relatively poorly, but showed the presence of vasopressin neurons immunocytochemically one month post-grafting. Homotopic grafting in the supraoptic nucleus, however, even failed to show surviving vasopressin neurons. Graft survival was improved by the use of donor tissue of fetuses younger than day 19. Parvocellular vasopressin cells were frequently seen, organized into clusters resembling the normal suprachiasmatic nucleus. However, magnocellular neurons, as normally seen in supraoptic and paraventricular nuclei, only survived grafting when taken between days 11 and 15 of fetal age. It was concluded that only immature vasopressin neurons survived grafting under the condition employed. Magnocellular neurons had a limited fiber outgrowth into the host brain and median eminence. Most large neurons only stained with non-specific neurophysin antiserum, not with specific vasopressin-associated neurophysin antiserum. Thin fibers of the parvocellular vasopressin neurons provided only occasional and sparse innervation of the host median eminence and lateral septum (one case), but several examples of massive fiber bundles running dorsally from graft into host brain were observed. These fibers terminated in the thalamic periventricular area, a nucleus that is normally innervated by the vasopressin neurons of the suprachiasmatic nucleus. The failure of the grafts to provide adequate vasopressinergic innervation of the host median eminence probably explains why none of the nearly 200 Brattleboro neonates operated upon showed any sign of relief of their diabetes insipidus. It suggests, however, that the present procedures might be useful in restoring central vasopressinergic functions in the developing Brattleboro rat.
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PMID:Vasopressin neuron survival in neonatal Brattleboro rats; critical factors in graft development and innervation of the host brain. 390 Aug 3

This chapter has reviewed briefly the neuroanatomy relevant to the synthesis and release of AVP and OXT. Osmoregulation and baroregulation of AVP secretion has been discussed in detail, emphasizing the importance of osmotic control under normal physiological conditions. The remainder of the text has covered the two major pathophysiological disturbances of AVP secretion. In considering diabetes insipidus a pragmatic approach has been taken in the differentiation of the causes of polyuria and its treatment. A similar approach has been applied to the syndrome of inappropriate antidiuresis. Brief mention was made of the function of OXT.
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PMID:Posterior pituitary function in health and disease. 636 55

We studied the pathophysiology, natural history, and genetic basis of familial neurohypophyseal diabetes insipidus (FNDI) in a caucasian kindred. Twelve members had polyuria and a deficiency of plasma vasopressin (AVP), which progressed in severity over time. Another had normal urine volumes and plasma AVP when first tested at age 3 yr, but developed severe FNDI a year later. For unknown reasons, one man had a normal urine volume despite severe AVP deficiency and a history of polyuria in the past. When the AVP-neurophysin-II gene was amplified and sequenced, exon 2/3 was normal, but 7 of 12 clones of exon 1 contained a base substitution (G-->A) predicting a substitution of threonine for alanine at the -1 position of the signal peptide. Restriction analysis found the mutation in all 14 affected members, but in none of the 41 controls or 19 adult members with normal urine volumes and plasma or urinary AVP (lod score = 5.7). The mutation was also found in 2 infants in whom AVP was normal when tested at 6 and 9 months of age. We hypothesize that a mutation in exon 1 of the AVP-neurophysin-II gene causes FNDI in this kindred by making an abnormally processed precursor that gradually destroys vasopressinergic neurons.
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PMID:Familial neurohypophyseal diabetes insipidus associated with a signal peptide mutation. 837 Jun 80

We studied the genetic basis of familial neurohypophyseal diabetes insipidus in a Japanese family. The members had polyuria and a deficiency of plasma vasopressin (AVP). Polymerase chain reaction (PCR) amplified exons of the AVP-neurophysin-II gene were subcloned and sequenced. Exons 1 and 3 were normal, but nucleotide 1884 Guanine (G) in exon 2 was substituted with Thymine (T), which induced a substitution of glycine (Gly) for valine (Val). To examine the presence of this mutation in the affected subjects, we designed two mutated primers. One of them induced a new endonuclease restriction site in the PCR fragments from normal, and the other induced a new endonuclease restriction site from patients with the mutation. DNA fragments from two affected members of this family were amplified with this primer, and the PCR products were digested by endonuclease and resolved by electrophoresis. The results indicated that these subjects had both normal and mutant alleles, indicating that the mutation was heterozygous. We concluded that this mutation caused neurohypophyseal diabetes insipidus in this family.
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PMID:A new type of familial central diabetes insipidus caused by a single base substitution in the neurophysin II coding region of the vasopressin gene. 862 36

We investigated the expression of neuronal nitric oxide synthase (nNOS) gene in the paraventricular (PVN) and supraoptic nuclei (SON) of rats with inherited diabetes insipidus (DI), using in situ hybridization histochemistry. The DI rats showed hypo-osmotic polyuria and polydipsia with arginine vasopressin (AVP) deficiency. The expression of nNOS gene in the PVN and SON in homozygous (di/di) rats was significantly increased in comparison to normal Wistar and heterozygous (di/+) rats. nNOS gene-expressing cells were distributed throughout the PVN and SON, including the divisions of AVP and oxytocin gene expressing cells in di/di rats. These results suggest that the expression of nNOS gene is upregulated in the magnocellular neurons in the PVN and SON of inherited DI rats.
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PMID:Upregulation of neuronal NOS mRNA in the PVN and SON of inherited diabetes insipidus rats. 946 64

We present a 10-year old boy with central diabetes insipidus (CDI) showing hyperintensity in a normal-sized posterior pituitary on magnetic resonance (MR) T1-weighted image (T1WI). He complained of nocturnal enuresis and polyuria. Daily urine volume increased to 4 to 5 L, and AVP plasma level was very low. Polymerase chain reaction (PCR)-amplified exons of the arginine vasopressin (AVP)-neurophysin (NP) II gene were sequenced. Nucleotide-1884 guanine in Exon 2 was substituted with thymine, which induced a substitution of glycine for valine at amino acid position 65 in the NP II moiety. However, MR imaging showed hyperintensity in the posterior pituitary on T1WI. These results suggest that the MR findings of the posterior pituitary in CDI may vary.
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PMID:Hyperintensity of posterior pituitary on MR T1WI in a boy with central diabetes insipidus caused by missense mutation of neurophysin II gene. 1160 68


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