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)

Chronically hyponatremic rats were subjected to various stressors in order to evaluate the possible contribution of magnocellular neurons to the regulation of ACTH secretion, since such rats have markedly inhibited secretion and synthesis of magnocellular arginine vasopressin (AVP) and oxytocin (OT). Stress caused by a novel environment or by insulin-induced hypoglycemia resulted in moderate increases in plasma ACTH, which were of similar magnitude in both hyponatremic and normonatremic rats, and these stressors caused no increase in plasma AVP and OT levels in either group of rats. However, when exposed to ether, hyponatremic rats exhibited a significantly blunted ACTH response compared to normonatremic controls (331 +/- 49 vs. 740 +/- 124 pg/ml; P less than 0.01, respectively), and plasma AVP levels were markedly increased in the normonatremic, but not in the hyponatremic, rats. Intravenous infusion of 2 M NaCl also caused an ACTH release in hyponatremic rats that was significantly smaller than that in their normonatremic counterparts (228 +/- 52 vs. 479 +/- 85 pg/ml; P less than 0.05, respectively), and in this case both plasma AVP and OT levels were markedly increased in the normonatremic, but not in the hyponatremic, rats. However, hyponatremic rats exhibited greatly increased plasma ACTH levels 2 and 96 h after adrenalectomy (ADX), which were statistically equivalent to the increases in ACTH levels in normonatremic rats after ADX. Seven days after ADX parvocellular neurons of the paraventricular nucleus showed strongly increased CRF-41 and AVP-neurophysin, but not OT-neurophysin, immunoreactivities in both normonatremic and hyponatremic rats. These results show that parvocellular CRF-41/AVP-producing neurons in the paraventricular nucleus are not inhibited by chronic hyponatremia, in contrast to magnocellular neurons, and suggest that ACTH secretion induced by ether or hypertonic saline, but not by novel environment or insulin-induced hypoglycemia, is partially mediated by magnocellular AVP and/or OT.
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PMID:Hyponatremia-induced inhibition of magnocellular neurons causes stressor-selective impairment of stimulated adrenocorticotropin secretion in rats. 184 2

Bilateral adrenalectomy (ADX) leads to increased ACTH synthesis and secretion. It is thought that endogenous glucocorticoids exert a feedback mechanism at both pituitary and brain levels. The present study has been performed in order to determine the effect of ADX on the release of hypothalamic neuropeptides with corticotropin-releasing activity (CRA) and if there exists a median eminence site of glucocorticoid action to regulate hypothalamic-pituitary-adrenal (HPA) function. Adrenalectomized and sham-operated male rats were killed at different periods after surgery (2, 5, 7 and 14 days) and trunk blood was collected for ACTH and corticosterone (B) concentrations measurement. Brain (median eminence, ME; and medial basal hypothalamus, MBH) and pituitary (anterior lobe, AP; and neurointermediate lobe, NIL) tissues were dissected in order to evaluate either peptide content or in vitro hormone release. The results indicate that ADX blunted plasma B levels and increased AP ACTH content and secretion in a time-related fashion up to the 14th day. ADX significantly decreased both CRF and CRA contents in the ME at all periods studied; ME arginine-vasopressin (AVP) increased 7 and 14 days after ADX. MBH CRF decreased after ADX, but returned to sham value 2 weeks later; similarly, MBH AVP decreased at all periods after ADX. Removal of endogenous glucocorticoids did not vary neither oxytocin (OXY) content in the ME and MBH nor AVP and OXY contents in the NIL. In our superfusion experiments, we found that ADX increased basal AVP release and did not change spontaneous CRF secretion from ME terminals. Dexamethasone (Dxm, 10 nM) diminished AVP but not CRF output by ME tissues from adrenalectomized rats. A direct relationship was found between ME CRF and 28 mM KCl (hK+)-induced CRF release by MEs from adrenalectomized rats. ME fragments from adrenalectomized rats were hyperresponsive to kH+ stimulation of AVP release. Dxm (10 nM) decreased the hK(+)-evoked CRF and AVP release by MEs from adrenalectomized rats. ADX and dexamethasone treatment did not influence basal and hK(+)-elicited ME OXY release. Additionally, a rapid glucocorticoid inhibitory effect on ACTH secretion by isolated AP cells from both sham and adrenalectomized rats was found, and an in vitro corticotrope hyporesponse to 0.63 nM CRF and 9.25 nM AVP stimulation during several days after ADX.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Changes in the hypothalamo-corticotrope axis after bilateral adrenalectomy: evidence for a median eminence site of glucocorticoid action. 184 20

Recent results have demonstrated altered corticotropin-releasing factor (CRF)-41 content of the neurointermediate lobe (NIL) of the pituitary gland in response to various manipulations including osmotic stimulation. This study was undertaken to determine whether changes in CRF-41 content of the NIL are accompanied by changes in intensity of CRF-41-like immunoreactivity (CRF-41-LI) of neurosecretory neurones of the hypothalamus in response to osmotic stimulation. Wistar rats of both sexes given either tap water ad libitum, 2% NaCl solution, or access to tap water was limited to 20 min daily, for 7 days. Subsets of rats from each group were adrenalectomized (ADX) or treated with dexamethasone (DEX). Thirty-six hour before perfusion with fixative consisting of buffered formaldehyde and picric acid, animals received 75 micrograms colchicine i.c.v. Forty micrometer thick vibratome sections were stained for CRF-LI, arginine vasopressin (AVP-LI) and oxytocin (OXY-LI) using the avidin-biotin-peroxidase complex method. In response to both types of osmotic stimulation magnocellular neurones of the paraventricular (PVN) and supraoptic nuclei (SON) showed increased CRF-LI, AVP-LI and OXY-LI, while CRF-LI of parvocellular perikarya of the PVN decreased. The enhanced CRF-LI seemed to appear in a subset of magnocellular neurones with OXY-LI but not AVP-LI. Increased staining intensities were also observed in magnocellular neurones in ADX rats challenged osmotically. In contrast, systemic DEX administration, as well as implantation of DEX in the area on the SON, sharply attenuated CRF-LI but not AVP-LI or OXY-LI of magnocellular neurones in osmotically stimulated rats.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Oxytocinergic neurons in rat hypothalamus. Dexamethasone-reversible increase in their corticotropin-releasing factor-41-like immunoreactivity in response to osmotic stimulation. 211 29

In the present study we report the properties of vasopressin (VP) receptors in the anterior pituitary gland and show that the number of these receptors is markedly affected by adrenalectomy and hypothalamic lesions. VP-binding activity was assayed in particulate fractions of rat anterior pituitary glands using tritium-labeled arginine VP ([3H] AVP) as tracer. In the presence of Mg2+ the radioligand interacted with a single class of high affinity, low capacity binding sites. Magnesium ions modulated the affinity of the receptors but had no effect on binding capacity. Guanine nucleotides decreased the amount of tracer bound in a dose-dependent manner by increasing the dissociation constant (Kd) of the binding reaction by approximately 2-fold. Increasing the concentration of Mg2+ did not prevent this effect. Bilateral adrenalectomy (ADX) decreased pituitary AVP-binding activity: binding fell by 30% 4 h after surgery and declined further to 10% or less of control at 4 days. The decrease in binding was primarily due to a reduction in the number of receptors. Daily administration of corticosterone inhibited the reduction of binding activity at 4 days in a dose-dependent manner. Destruction of hypophyseotropic VP neurons by means of surgical lesioning of the hypothalamic paraventricular nucleus or the medial basal hypothalamus abolished the effect of ADX on pituitary AVP binding at 24 h but only attenuated the degree of receptor loss at 4 days. Furthermore, the lesions themselves caused a significant (approximately 30%) reduction in receptor number 4-7 days after hypothalamic surgery. Adrenalectomy reduced pituitary AVP-binding activity in homozygous (di/di) Brattleboro rats. The extent as well as the time course of the loss of receptor activity resembled that in normal rats. Rat anterior pituitary segments were exposed to synthetic CRF, AVP, or oxytocin (all 10(-7) M) for 4 h in vitro, and [3H] AVP-binding activity was subsequently determined. Both AVP and oxytocin reduced the amount of radioligand bound, while CRF had no effect. These observations allow the following conclusions: Magnesium ions and guanine nucleotides modulate the affinity of pituitary AVP receptors by different mechanisms and have no effect on binding capacity; Pituitary receptors for AVP are regulated by the amount of AVP released by paraventricular nucleus neurons as well as through a mechanism that requires the presence of corticosterone; Homozygous Brattleboro rats may respond to ADX by increased hypothalamic release of an endogenous ligand for pituitary AVP receptors.
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PMID:Pituitary binding of vasopressin is altered by experimental manipulations of the hypothalamo-pituitary-adrenocortical axis in normal as well as homozygous (di/di) Brattleboro rats. 316 22

CRF-containing parvocellular axons in the external zone of the rat median eminence were classified as vasopressin-containing (CRF+/AVP+) and vasopressin-deficient (CRF+/AVP-) subpopulations based on post-embedding electron microscopic immunocytochemical staining of serial ultrathin sections for CRF, AVP and the other peptides derived from the AVP precursor: AVP-associated neurophysin (NP-AVP) and the C-terminal glycopeptide (GP). In normal animals, the CRF+/AVP+ and CRF+/AVP- subpopulations were approximately equal in terms of detectable axonal swellings. Three to 14 days after adrenalectomy (ADX), the CRF+/AVP+ and CRF+/AVP- subpopulations represented about 95% and 5%, respectively, of total CRF+ swellings. This change was due to a 90% decrease in the absolute number of detectable CRF+/AVP- swellings after ADX, whereas the absolute number of detectable CRF+/AVP+ swellings rose by less than 20%. These changes were completely blocked by administering the glucocorticoid agonist dexamethasone throughout the period after ADX. The results suggest that the CRF+/AVP+ and CRF+/AVP- subpopulations of neurosecretory axons in the external zone of the median eminence respond differently to ADX, indicating that they are independently regulated by glucocorticoids.
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PMID:Vasopressin-containing and vasopressin-deficient subpopulations of corticotropin-releasing factor axons are differentially affected by adrenalectomy. 349 95

Immuno- and hybridization histochemical methods were used to examine a possible role for adrenocorticotropic hormone (ACTH) in regulating the expression of corticotropin-releasing peptides in rat hypothalamus. Densitometric assessments of relative levels of mRNAs encoding corticotropin releasing factor (CRF), arginine vasopressin (AVP) and oxytocin (OT) in the parvocellular division of the paraventricular nucleus (PVH) were carried out in intact, adrenalectomized (ADX) and hypophysectomized (HYPOX) animals. Both surgeries resulted in comparable increases in relative levels of CRF and AVP transcripts in the parvocellular PVH; no effects on OT mRNA in this compartment were evident. In a second experiment, ACTH or saline vehicle were administered systemically via osmotic minipump for seven days to rats submitted to both HYPOX and ADX surgeries. Lower replacement doses of ACTH reduced the number of detectable AVP-immunoreactive (AVP-ir) cells in the parvocellular PVH to 53% of that seen in vehicle-treated HYPOX/ADX controls; the number of CRF-IR cells was not significantly affected. Higher doses of ACTH resulted in counts of AVP- and CRF-IR neurons that were reduced to 32% and 70%, respectively, of control values. Staining patterns for the two peptides in the external lamina of the median eminence generally followed the cell count data. Neither densitometric nor combined immunohistochemical (for CRF-ir) and hybridization histochemical (for AVP mRNA) assays revealed any marked effect of ACTH on AVP mRNA expression in the parvocellular PVH of HYPOX/ADX rats. The results indicate that ACTH is capable of inhibiting corticotropin-releasing peptide, but not mRNA, expression in hypophysiotropic neurons. The mechanisms underlying these effects remain to be fully clarified.
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PMID:Evidence for short-loop feedback effects of ACTH on CRF and vasopressin expression in parvocellular neurosecretory neurons. 854 50

The prohormone convertases (PCs) are processing enzymes that activate proproteins via cleavage at specific single or pairs of basic residues. The hypothalamic paraventricular nucleus (PVN) and supraoptic nucleus (SON) are primary sites of biosynthesis of several neuroendocrine hormone precursors, including provasopressin (pro-AVP), pro-oxytocin (pro-OT), and procorticotrophin-releasing hormone (pro-CRH), which require post-translational processing to yield active products. Using in situ hybridization, we observed PC1 and PC5 mRNAs in PVN and SON magnocellular neurons, while PC2 mRNA was observed in both magnocellular and parvocellular PVN neurons as well as magnocellular SON neurons. Similar to furin, PC7 mRNA was expressed throughout the PVN and SON, whereas PACE4 mRNA levels were undetectable. Both immunohistochemical and Western blot studies were performed to demonstrate the presence of PC proteins and forms in the PVN and SON. Using double-labeling in situ hybridization, we examined the cellular colocalization of each PC mRNA with pro-AVP, pro-OT, and pro-CRH mRNAs in PVN and SON. PC1 mRNA was colocalized with both AVP and OT mRNA in PVN and SON magnocellular neurons. All AVP, OT, and CRH neurons expressed PC2. In contrast, PC5 mRNA was colocalized only with OT mRNA. We examined the effects of adrenalectomy (ADX) on PVN PC mRNA levels. PC1 mRNA levels were increased selectively within CRH/AVP parvocellular neurons but were unchanged in PVN magnocellular AVP or OT neurons. These results established the anatomical organization of each convertase and proneuropeptide substrates in the PVN and SON and suggested potential roles for each enzyme under resting and stimulated conditions.
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PMID:Cellular localization of the prohormone convertases in the hypothalamic paraventricular and supraoptic nuclei: selective regulation of PC1 in corticotrophin-releasing hormone parvocellular neurons mediated by glucocorticoids. 898 79

The effects of cytokines in stimulating neurohypophysial hormone release have not been well characterized. In the present study, we have investigated the effect of intraperitoneal injection of recombinant human interleukin (IL)-1 beta on oxytocin release in sham-operated controls, adrenalectomized (ADX) rats and ADX rats given either low or high doses of the synthesis glucocorticoid dexamethasone. In a second study, we determined the effect of central injection of IL-1 beta on both oxytocin and arginine vasopressin (AVP) release in sham-operated and ADX rats. We were unable to demonstrate an increase in plasma oxytocin in intact rats in response to intraperitoneal injection of IL-1 beta. In contrast, we found a substantial and sustained increase in plasma oxytocin concentrations in ADX rats. This stimulation was abolished by treatment with dexamethasone at both the low and high doses. Following central injection of IL-1 beta, we were unable to demonstrate any increase in either oxytocin or AVP, despite the ability of this dose of cytokine to stimulate the hypothalamo-pituitary-adrenal axis, as evidenced by increased circulating corticosterone. It appears that circulating glucocorticoids may exert a tonic inhibitory effect on the release of oxytocin in response to peripheral stimulation by IL-1 beta.
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PMID:Interleukin-1 beta-induced effects on plasma oxytocin and arginine vasopressin: role of adrenal steroids and route of administration. 926 47

Twenty days after bilateral adrenalectomy (ADX) or immediately after the last of three 6-h long immobilization periods, the levels of hypothalamic and neurohypophyseal L-[35S]Cys-labeled arginine vasopressin (AVP), oxytocin (OT), and somatostatin-14 (SRIF) (only stressed animals) were measured simultaneously in male Wistar rats, after third ventricular administration of the labeled precursor, via guide-cannulae. The acetic acid-extracted labeled peptide fractions were purified by two sequential HPLC steps. After a 4 h period of labeling, only L-[35S]Cys-AVP was selectively increased in the hypothalami of ADX-ized rats, compared to the sham-operated animals, possibly reflecting a significant activation of the paraventricular parvocellular (PVC) AVP/corticotropin-releasing factor (CRF) neurons. The increased accumulation of neurohypophyseal L-[35S]Cys-labeled AVP and OT in these animals, without changes in the endogenous levels of these peptides, as measured by UV absorbance, also suggests a moderate activation of the magnocellular (MGC) AVP and OT neurons, as a consequence of adrenal insufficiency. In response to immobilization stress, levels of L-[35S]Cys-OT were selectively increased in the hypothalami and corresponding neurohypophyses, 2 h and 4 h after receiving the label, concomitantly with a statistically significant reduction in the stores of OT in the neural lobes. AVP and SRIF biosynthesis remained unaffected by immobilization; the neurohypophyseal AVP stores likewise remained unchanged. These observations suggest the selective activation of MGC-OT neurons in response to chronic immobilization stress. Selective increases in hypothalamic L-[35S]Cys-AVP in ADX-ized rats, and in hypothalamic L-[35S]Cys-OT in chronically stress-immobilized rats, are presented as a measure of PVC-AVP/CRF and MGC-OT neuronal activation, respectively.
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PMID:Vasopressinergic, oxytocinergic, and somatostatinergic neuronal activity after adrenalectomy and immobilization stress. 956 8

The neuropeptides angiotensin II (AngII) and oxytocin (OT) play important but opposing roles in the regulation of sodium appetite in the rat, AngII as a stimulatory peptide and OT as an inhibitory peptide. Adrenal steroids increase the density of AngII receptors in brain following in vivo administration, although the neuroanatomical and subtype specificity have not been thoroughly examined. Furthermore, previous studies demonstrate that adrenalectomy (ADX) leads to a reduction in OT receptors, although regions associated with sodium appetite remain to be examined. In the present study, quantitative receptor autoradiography was used to locate regions where perturbations in circulating adrenal steroids affect the density of oxytocin receptors and the angiotensin receptor subtypes AT1 and AT2. The results show that ADX results in a small, but significant decrease in AT1 expression in the paraventricular nucleus of the hypothalamus, subfornical organ, and the area postrema. That this effect is reversed by either aldosterone or low-dose corticosterone replacement suggests that occupancy of the mineralocorticoid receptor is responsible for the steroid effect. No changes were observed in AT2 or OT receptors in nuclei associated with sodium appetite, indicating that perturbations in adrenal steroids did not affect these receptors in brain regions implicated in the control of salt appetite.
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PMID:Adrenal steroid regulation of central angiotensin II receptor subtypes and oxytocin receptors in rat brain. 975 19


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