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)

We have investigated the roles of full-length and carboxyl-terminus-truncated forms of the subtilisin-like prohormone convertase SPC3 in the processing of the radiolabeled vasopressin and oxytocin precursors, in vitro. We found SPC3 cleaves provasopressin at both the vasopressin-neurophysin and neurophysin-glycopeptide processing sites. Prooxytocin is cleaved by SPC3 at the oxytocin-neurophysin cleavage site. However, our results reveal differences in processing of provasopressin by the different molecular forms of SPC3. In incubations where the rate of autocatalytic carboxyl-terminus truncation of SPC3 was dramatically reduced, 86-kDa SPC3, which has an unprocessed carboxyl terminus, cleaved provasopressin at the neurophysin-glycopeptide junction. Cleavage at the vasopressin-neurophysin junction only occurred with the appearance of carboxyl-terminus-truncated forms of the enzyme. Incubations containing 64-kDa SPC3 or 64-kDa SPC3-T, a recombinant form of SPC3 truncated 14 amino acids beyond the conserved carboxyl-terminal "P-domain," rapidly cleaved provasopressin at both the vasopressin-neurophysin and neurophysin-glycopeptide junctions. Our results also suggest that prooxytocin is unable to be cleaved by the 86-kDa form of SPC3. We propose that SPC3 should be considered as a candidate endoprotease in the biosynthesis of vasopressin. Furthermore, we suggest that the carboxyl terminus of SPC3 alters the cleavage specificity of SPC3.
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PMID:Differential cleavage of provasopressin by the major molecular forms of SPC3. 952 85

Synthetic glucocorticoids have become an important clinical tool with which to advance fetal lung maturation in women at risk of early preterm birth, and this has succeeded in reducing neonatal mortality and morbidity from respiratory distress syndrome. Although previous studies have shown that glucocorticoids have deleterious consequences on fetal development, there is little information regarding the effects of clinically relevant repeated maternal doses of glucocorticoids on fetal growth and hypothalamic-pituitary-adrenal (HPA) function. We hypothesised that repeated prenatal exposure to increased concentrations of glucocorticoids would alter fetal growth and HPA axis development. Pregnant ewes were injected with betamethasone (0.5 mg/kg) or vehicle at 104, 111 and 118 days of gestation (term 150 days). Animals were sacrificed at 125 and 146 days of gestation, at which time fetal weights were recorded. Maternal and fetal blood samples were gathered and fetal tissue collected. Maternal oestradiol concentrations were significantly greater than those in controls at 125 days of gestation, but were not different at 146 days. Maternal plasma progesterone concentrations were similar between groups at both 125 and 146 days of gestation. Weight at birth was significantly reduced by 23% at 125 days and 19% at 146 days of gestation (P<0.05) after exposure to glucocorticoid. Cord plasma ACTH concentrations were not significantly different between groups at day 125, but were significantly increased in day 146 fetuses of ewes that had received betamethasone (P<0.05). Cord plasma cortisol concentrations followed the same trend, although differences were not statistically significant. Cord plasma corticosteroid binding capacity (CBC) was significantly increased at 125 days of gestation in fetuses of betamethasone-treated animals (P<0.05), but not at 146 days of gestation. To examine the mechanisms regulating the increase in cord plasma ACTH of 146-day fetuses, we used in situ hybridisation to determine the distribution and levels of mRNA encoding key pituitary and hypothalamic neuropeptides of the HPA axis. In pituitaries of 146-day fetuses, there were no significant differences in the regional pattern of distribution or amounts of pro-opiomelanocortin (POMC) mRNA between betamethasone-treated animals and controls, in either the pars intermedia or the inferior and superior regions of the pars distalis. Neither prohormone convertase (PC)-1 nor PC-2 mRNA levels in pituitaries of 146-day fetuses were significantly different between treatment groups. After maternal betamethasone, immunoreactive ACTH peptide content in the fetal pars distalis was not different but glucocorticoid receptor (GR) mRNA levels in the pars distalis were increased significantly (P<0.05). No significant difference in distribution pattern or concentrations of corticotrophin-releasing hormone (CRH) mRNA, GR mRNA, oxytocin mRNA and pre-proenkephalin mRNA were found in hypothalami from fetuses at 146 days of gestation after betamethasone treatment. We conclude that antenatal betamethasone given to pregnant sheep in a manner similar to that used in human obstetric practice results in reduced weight at birth at 125 and 146 days, and altered basal cord levels of plasma ACTH and corticosteroid binding capacity, but these changes are not reflective of changes in steady state concentrations of POMC and CRH mRNA in the fetal pituitary or hypothalamus.
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PMID:Effects of repeated maternal betamethasone administration on growth and hypothalamic-pituitary-adrenal function of the ovine fetus at term. 1075 38

Arginine vasopressin (AVP) is synthesized in parvocellular- and magnocellular neuroendocrine neurons in the paraventricular nucleus (PVN) of the hypothalamus. Whereas magnocellular AVP neurons project primarily to the posterior pituitary, parvocellular AVP neurons project to the median eminence (ME) and to extrahypothalamic areas. The AVP gene encodes pre-pro-AVP that comprises the signal peptide, AVP, neurophysin (NPII), and a copeptin glycopeptide. In the present study, we used an N-terminal copeptin antiserum to examine copeptin expression in magnocellular and parvocellular neurons in the hypothalamus in the mouse, rat, and macaque monkey. Although magnocellular NPII-expressing neurons exhibited strong N-terminal copeptin immunoreactivity in all three species, a great majority (~90%) of parvocellular neurons that expressed NPII was devoid of copeptin immunoreactivity in the mouse, and in approximately half (~53%) of them in the rat, whereas in monkey hypothalamus, virtually all NPII-immunoreactive parvocellular neurons contained strong copeptin immunoreactivity. Immunoelectron microscopy in the mouse clearly showed copeptin-immunoreactivity co-localized with NPII-immunoreactivity in neurosecretory vesicles in the internal layer of the ME and posterior pituitary, but not in the external layer of the ME. Intracerebroventricular administration of a prohormone convertase inhibitor, hexa-d-arginine amide resulted in a marked reduction of copeptin-immunoreactivity in the NPII-immunoreactive magnocellular PVN neurons in the mouse, suggesting that low protease activity and incomplete processing of pro-AVP could explain the disproportionally low levels of N-terminal copeptin expression in rodent AVP (NPII)-expressing parvocellular neurons. Physiologic and phylogenetic aspects of copeptin expression among neuroendocrine neurons require further exploration.
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PMID:Variation of pro-vasopressin processing in parvocellular and magnocellular neurons in the paraventricular nucleus of the hypothalamus: Evidence from the vasopressin-related glycopeptide copeptin. 3289 51