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

Glucocorticoid hormones suppress the secretion of ACTH evoked by secretagogues such as CRF and arginine vasopressin. In this study, we investigated the effects of glucocorticoids on ACTH release induced by oxytocin (OT) and on intracellular free calcium ion levels in corticotropes prepared from the adenohypophyses of female Wistar rats. Pulsatile additions of physiological concentration of OT (10 nM) to superfused anterior pituitary cells caused pulsatile ACTH release about 4-fold above basal secretion with similar peak amounts of ACTH during subsequent OT pulses. Exposure of the cells to corticosterone (100 nM) or to a selective glucocorticoid receptor agonist RU 28362 (100 nM) for 30 min suppressed OT-stimulated but not basal ACTH release by approximately 60%. Inhibition gradually disappeared during subsequent pulses of OT in the absence of corticosterone. Pretreatment with the selective antagonist RU 38486 (1 microM) completely blocked the inhibitory effect of corticosterone on OT-induced ACTH secretion. Changes in free cytosolic calcium levels in single cultured pituitary cells were measured using the calcium indicator Fura-2. OT caused calcium transients in corticotropes, which were identified by immunocytochemistry. They responded in a similar manner to a second OT stimulus when preincubated for 30 min with corticosterone (1 microM) or with RU 28362 (1 microM). Our data indicate that glucocorticoids, via glucocorticoid receptors, rapidly inhibit OT-stimulated ACTH secretion by corticotropes without affecting intracellular calcium transients due to OT. Therefore, we conclude that rapid inhibition of ACTH release by glucocorticoids interferes with cellular signal transduction beyond the step of calcium mobilization.
 ...
PMID:Glucocorticoids rapidly inhibit oxytocin-stimulated adrenocorticotropin release from rat anterior pituitary cells, without modifying intracellular calcium transients. 838 Oct 78

The concentration of immunoreactive, placentally derived CRH is increased in the peripheral circulation during the third trimester of human pregnancy. However, the function of this placental CRH is entirely unknown. A number of observations have led us to believe that CRH might influence myometrial contractility and, hence, parturition via specific receptor mechanisms. 1) In idiopathic preterm labor, plasma immunoreactive-CRH concentrations are significantly elevated compared to control values. 2) CRH and oxytocin exhibit a marked synergistic effect on myometrial contractility which is prostaglandin dependent and can be inhibited by the CRH receptor antagonist [alpha-helical CRF-(9-41)]. In view of this, we searched for specific CRH-binding sites in myometrial tissue obtained at biopsy from pregnant (cesarian section) and nonpregnant (hysterectomy) patients. To test for the presence of CRH receptors, we prepared myometrial membranes and performed binding studies using [125I]tyr-o-CRH as a ligand. The binding was found to be pH, time, temperature, and divalent cation concentration dependent and was fully reversible on addition of 1 microM unlabeled ovine CRH. In both tissues, there was a single, specific, homogenous, high affinity population of CRH receptors. Scatchard analysis of the specific binding sites revealed dissociation constants of 250-300 and 30-60 pM for the nonpregnant and pregnant myometrium, respectively. This compares with dissociation constants of 130 pM (rat anterior pituitary receptor) and 100 pM (human CRH-binding protein). This would mean that in the nonpregnant state, the equilibrium for binding is in favor of the binding protein, but during the later stages of pregnancy, the change in affinity of the receptor alters the binding in favor of the myometrial receptor.
 ...
PMID:The identification of a human myometrial corticotropin-releasing hormone receptor that increases in affinity during pregnancy. 838 45

ACTH release by the anterior pituitary lobes of 8-day-old newborn rats (males and females) in the presence of rat corticotrophin-releasing factor (rCRF), arginine vasopressin (AVP) and oxytocin, given alone or in association, was measured in vitro. Rat CRF and AVP induced a dose-dependent release of ACTH in both sexes, while oxytocin was unable to stimulate ACTH secretion except at the highest dose tested. No sex-related difference was noted for any of the responses. Oxytocin (1 nmol/l) potentiated the response to rCRF (0.20 nmol/l) by the anterior pituitary lobes of females but not by those of males. This oxytocin potentiation was abolished when female newborn rats were injected at birth with testosterone (1 mg). AVP (1 nmol/l) alone stimulated ACTH release from the anterior pituitary lobes of the newborn rats of both sexes and markedly potentiated the ACTH response to rCRF. Although no difference between the sexes was noted for basal levels of AVP and oxytocin in the hypothalamus, the neurointermediate lobe and the peripheral plasma, the present data on the sex-related effect of oxytocin on the newborn adenohypophysis could, in part, explain why ACTH release in response to ether stress was previously reported to be more lasting in females than in males on day 8 postpartum.
 ...
PMID:ACTH secretion from isolated hypophysial anterior lobes of male and female newborn rats: effects of corticotrophin-releasing factor, arginine vasopressin and oxytocin alone or in combination. 838 13

The most established physiological function of oxytocin is to induce milk ejection from the mammary gland of lactating animals. It is now known that during lactation oxytocin is released pulsatively following brief periods of burst-like and synchronous activation of many thousands of oxytocin cells in the hypothalamus. The mechanism generating such activity in oxytocin cells has been extensively studied, but it has not been fully understood yet. To explain that suckling stimuli produce a recurrence of milk ejection bursts of oxytocin cells without any change in their background activity, a gating mechanism has been hypothesized. In the excitatory transmission of afferent signals of the milk ejection reflex, alpha adrenergic receptors are indicated to be involved. Among neuropeptides, oxytocin and CRF are potent facilitatory factors. As non-neurochemical factors that facilitate milk ejection bursts of oxytocin cells, there are osmotic stimuli, neurohypophyseal stimulation and vaginal distention. During the lactation period, responsiveness of oxytocin cells to various stimuli such as stress, osmotic stimuli and CCK is markedly reduced. The cause of the change has not been discovered, but it is assumed that the reduction in responsiveness may enable the animal to adapt to the large demands for the hormone during the lactation period.
 ...
PMID:[Control of oxytocin secretion in lactation]. 839 67

The relative importance of the paraventricular (PVN) and the supraoptic nuclei (SON) for the secretion of oxytocin was evaluated by comparison of stress-induced oxytocin release under normal conditions, in the absence of vasopressin and/or corticoliberin (CRF). We introduced an incomplete anterolateral cut (iALC) around the mediobasal hypothalamus designed to leave intact the SON-neurohypophysial connections but to inflict damage to the nerve fibers from the PVN. The studies were performed in conscious cannulated rats using immobilization as the stress stimulus. Stress-induced oxytocin release was found in heterozygous Brattleboro rats as well as in homozygous animals lacking vasopressin, yet in the latter it was less pronounced and in both cases it was prevented by iALC. In Wistar rats, stress-induced oxytocin release was markedly reduced after iALC and absent after PVN lesion. Both hypothalamic interventions failed to influence basal oxytocin levels and resulted in a similar reduction of ACTH release. It is concluded that a functional diversity exists between the hypothalamic magnocellular nuclei. At least in relation to immobilization stress, the PVN is essential for stress-induced oxytocin release and it is evident that the SON without the PVN cannot preserve oxytocin secretion during stress.
 ...
PMID:Paraventricular and supraoptic nuclei of the hypothalamus are not equally important for oxytocin release during stress. 841 14

Steroid-metabolizing enzymes modulate the effects of androgens on brain differentiation and function, but no similar enzymatic system has been demonstrated for adrenocorticosteroids which exert feedback control on the hypothalamus. 11 beta-Hydroxysteroid dehydrogenase (11 beta-OHSD) rapidly metabolizes physiological glucocorticoids (corticosterone, cortisol) to inactive products, thereby regulating glucocorticoid access to peripheral mineralocorticoid and glucocorticoid receptors in a site-specific manner. Using in-situ hybridization, we found expression of 11 beta-OHSD mRNA in neurones of the hypothalamic paraventricular nucleus (PVN) where corticotrophin-releasing factor-41 (CRF-41) is synthesized and from where it is released into hypophysial portal blood. Administration of glycyrrhetinic acid (GE), a potent 11 beta-OHSD inhibitor, decreased CRF-41 release into hypophysial portal blood in the presence of unchanged circulating glucocorticoid levels, suggesting that 11 beta-OHSD regulates the effective corticosterone feedback signal to CRF-41 neurones. These effects of GE were not observed in adrenalectomized animals, demonstrating dependence on adrenal products. In contrast, GE led to two- to threefold increases in arginine vasopressin and oxytocin release into portal blood, effects also dependent upon intact adrenal glands. These results suggest that 11 beta-OHSD in the PVN, and possibly other sites, may represent a novel and important control point of corticosteroid feedback on CRF-41 release in vivo.
 ...
PMID:The 11 beta-hydroxysteroid dehydrogenase inhibitor glycyrrhetinic acid affects corticosteroid feedback regulation of hypothalamic corticotrophin-releasing peptides in rats. 847 34

We investigated the chemical and anatomical features of nitric oxide synthase (NOS)-containing neurons in the paraventricular and supraoptic nuclei in the rat hypothalamus using combinations of enzyme histochemistry, in situ hybridization and immuno-histochemistry. Neurons expressing NOS mRNA completely overlapped with NADPH-diaphorase-positive neurons. Topographical distribution of NOS was segregated from that of CRF-containing parvicellular neurons in the posterior paraventricular nucleus but overlapped with that of magnocellular neurons. In the paraventricular nucleus, 70% of oxytocin neurons contained NOS, which corresponded to one half of NOS neurons. About one third of vasopressin-immunoreactive neurons were NADPH-diaphorase-positive and the same proportion of NADPH-diaphorase-positive neurons were vasopressin-immunoreactive. In the supraoptic nucleus, 50% of oxytocin neurons were NADPH-diaphorase-positive, which corresponded to 40% of NOS neurons. About 25% of vasopressin neurons were NADPH-diaphorase-positive, and 30% of NADPH-diaphorase-positive neurons were vasopressin-immunoreactive. When NADPH-diaphorase histochemistry was performed first, subsequent immunostaining was markedly perturbed. Using fluoro-gold as a retrograde tracer, 4% of NADPH-diaphorase-positive neurons were shown to contribute to the descending projection to the spinal cord. About 40%-50% of NADPH-diaphorase-positive neurons exhibited Fos immunoreactivity after injection of lipopolysaccharide or hypertonic saline, while only 10%-15% of these neurons expressed Fos in response to immobilization or pain. Endogenous NO may be involved in the regulation of magnocellular functions, especially when the internal environment is disturbed.
 ...
PMID:Nitric oxide synthase-containing magnocellular neurons of the rat hypothalamus synthesize oxytocin and vasopressin and express Fos following stress stimuli. 895 94

Adrenocorticotropin (ACTH) secretion depends primarily on hypophysiotrophic factors released from neurons of the paraventricular nucleus of the hypothalamus. However, the neurochemical factors controlling these neurons, in particular neuropeptides, have had little investigation. In this study, we have investigated the role of neurotensin in the regulation of the different components of the hypothalamo-pituitary-adrenal (HPA) axis under basal and stress conditions in rats. For this purpose, animals were implanted with bilateral cannulae filled with crystals of the neurotensin antagonist, SR 48692, and which were located above the paraventricular nucleus. Five days after surgery, the effects of SR 48692 implants were studied on basal and stress-induced secretion of ACTH and corticosterone. Such treatment did not modify plasma levels of ACTH and corticosterone in basal conditions but reduced ACTH but not corticosterone levels after tail cut procedure. After an exposure to a novel environment for 30 min, both ACTH and corticosterone plasma levels were reduced in the SR 48692-treated group. In situ hybridization studies revealed that chronic administration of SR 48692 induced a significant reduction of CRF mRNA levels in the parvocellular division of the paraventricular nucleus of the hypothalamus. In addition, a 2-fold increase in basal levels of plasma vasopressin associated with an increase in vasopressin mRNA levels in the magnocellular neurons of the paraventricular nucleus was also detected. Finally, the basal plasma levels of oxytocin were not affected by the same treatment. Taken together, these findings strongly suggest that endogenous neurotensin in the paraventricular nucleus plays a tonic stimulatory role on HPA axis activity and an inhibitory effect on vasopressin secretion.
 ...
PMID:Endogenous neurotensin regulates hypothalamic-pituitary-adrenal axis activity and peptidergic neurons in the rat hypothalamic paraventricular nucleus. 914 89

We have studied the effects of long-term social isolation of male Wistar rats, after early weaning (16 days), on the activity of the hypothalamo-pituitary-adrenal (HPA) axis. In addition to studying basal HPA activity, the response of the HPA axis to 15 min of immobilization stress was examined. Plasma corticosterone concentrations were measured, and the relative weights of adrenal glands, thymus, and testes were obtained, the latter to check whether gonadal function was affected by the isolation paradigm. Moreover, we carried out a quantitative immunohistochemical study of pituitary ACTH and its hypothalamic secretagogues: CRF, arginine vasopressin (AVP), and oxytocin (OT), both at the level of the synthesizing cell bodies in the hypothalamic paraventricular nucleus and of the releasing fibers in the median eminence (ME). Body weight and daily consumption of food and water were not altered, but social isolation caused a reduction in plasma corticosterone levels, both under basal and stress-stimulated conditions; this was correlated with an increased thymus weight, without affecting adrenal or testicular weights. The immunohistochemical study revealed that isolation caused a smaller increase in the number of ACTH-immunoreactive cells in the pars distalis of the anterior pituitary after exposure to restraint stress, as compared with control animals. This result indicates that fewer corticotrophs were activated by restraint stress in isolated animals, such cells being smaller and exhibiting a smaller ACTH-immunoreactive area than in control animals. Isolated animals also showed an increase in the content of CRF-ir fibers in the ME and a smaller decrease in the neuropeptide immunoreactivity after stress than that observed in control animals. This result could indicate a reduced release of CRF into the portal vasculature in response to acute stress and may partially explain the reduced activation of corticotrophs observed in the pituitary of isolated animals. However, no changes were found in the content of CRF, AVP, or OT within the paraventricular nucleus, nor of the AVP or OT content in the ME. The results of this study show that long-term social isolation after early weaning caused a hypofunction of the HPA axis in the adult rat. This hypofunction was particularly evident after exposure to an acute stressor, suggesting a desensitization of this axis to stressful stimuli.
 ...
PMID:Neuroendocrine and immunocytochemical demonstrations of decreased hypothalamo-pituitary-adrenal axis responsiveness to restraint stress after long-term social isolation. 944 28

Tract-tracing techniques in combination with immunohistochemistry and in situ hybridization were used in intact and operated rats (hypothalamic lesions, transections of neuronal pathways) to localize and characterize neuronal connections between the hypothalamus and autonomic centers. Viscerosensory and somatosensory signals which relay in the spinal cord and the medulla oblongata reach the hypothalamus through various catecholaminergic and noncatecholaminergic neuronal pathways. Vice versa, the hypothalamus influences autonomic activities through humoral and neurohumoral pathways. Descending hypothalamic efferents carry feedback signals to viscerosensory and brainstem catecholaminergic neurons and regulatory inputs to parasympathetic (dorsal vagal nucleus) and sympathetic (thoracolumbar intermediolateral cell column) preganglionic neurons. These fibers arise mainly from neurons of the paraventricular, arcuate, perifornical, and dorsomedial nuclei and the lateral hypothalamus. The major neuroanatomical observations are the following: (1) pathways between the hypothalamus and autonomic centers are bidirectional: the ascending and descending fibers may use the same avenues; (2) the descending axons are mainly peptidergic (CRF, vasopressin, oxytocin, somatostatin, enkephalin, POMC, and cANP), while the ascending fibers are both peptidergic (enkephalin, NPY, neurotensin, dynorphins) and catecholaminergic; (3) descending hypothalamic axons terminate directly on the sensory, preganglionic, and catecholaminergic neurons in the medulla and the spinal cord; (4) hypothalamic projections to the autonomic centers are always bilateral; (5) while medullary autonomic and catecholaminergic fibers innervate hypothalamic neurons directly, spinohypothalamic axons are relayed on neurons in the lateral hypothalamus.
 ...
PMID:Interconnections between the neuroendocrine hypothalamus and the central autonomic system. Geoffrey Harris Memorial Lecture, Kitakyushu, Japan, October 1998. 1056 79


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>