Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0406810 (NAME)
 13,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cushing's syndrome of adrenal origin encompasses different entities: besides the occurrence of adenoma and carcinoma, a not homogeneous group includes the ACTH-independent macro- or micronodular bilateral hyperplasia and the familial pigmented nodular hyperplasia (Carney's syndrome). Moreover, isolated cases of immunological origin and food-dependence have recently described. On clinical grounds no major characteristics may help to identify the adrenal origin of Cushing's syndrome, except for few situations as carcinoma or nodular dysplasia. Laboratory investigations of patients with adrenocortical tumor are based on ACTH and cortisol determinations in basal conditions and in response to high dose dexamethasone and CRH tests. However, isolated diagnostic problems may occur, as the presence of a black adrenocortical adenoma or the uncommon persistence of a circadian rhythmicity of glucocorticoid secretion. The evaluation of new markers of bone turnover (BGP, ICTP) and of collagen turnover (PIIINP) confirms the existence of corticosteroid-induced bone and collagen damages and may also be a useful prognostic index after treatment. Although up to now food-dependent Cushing's syndrome appears to be very rare, the adrenocortical sensitivity to GIP has been investigated in patients with either pituitary Cushing's disease, or clinically silent adrenal masses. No evidence of GIP-dependent cortisol secretion during the peptide infusion or after endogenous stimulation by OGTT was observed in any case. Since the wide availability of sensitive and noninvasive imaging techniques (CT and NMR), in recent years the finding of incidentalomas has become fairly common. In patients with incidentaloma abnormalities of the endocrine function are frequently encountered, and the "preclinical" Cushing's syndrome is increasingly recognized.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:[Clinical and preclinical aspects of adrenal Cushing syndrome]. 765 Dec 81

Nitric oxide synthase, an enzyme responsible for nitric oxide (NO) formation has been found in the hypothalamic paraventricular nucleus and median eminence, structures closely associated with regulation of the pituitary activity, and the pituitary gland itself. Nitric oxide modulates the stimulated release of CRH from the rat hypothalamus in vitro, which suggests its role in regulating the secretion of ACTH from the pituitary corticotrops and of corticosterone from the adrenal cortex. The purpose of the present study was to elucidate the yet unknown role of endogenous NO in the HPA response to central cholinergic stimulation in conscious rats. Neither L-arginine an NO precursor, nor the NO synthase blockers N omega-nitro-L-arginine methyl ester (L-NAME) and N omega-nitro-L-arginine (L-NNA) caused any consistent changes in the basal serum corticosterone levels. L-arginine, given in higher doses (120-150 mg/kg ip) 15 min prior to icv carbachol (2 micrograms), markedly diminished the carbachol-induced rise in corticosterone secretion. Systemic pretreatment with the nitric oxide synthase inhibitor L-NAME (5 mg/kg) significantly raised the carbachol-elicited corticosterone response, while addition of L-arginine completely blocked the effect of L-NAME. A similar increase in the carbachol-induced corticosterone response was produced by icv pretreatment with L-NAME (2 micrograms), indicating a central site of the NO interaction with cholinergic stimulation of the HPA response. L-NAME is a weak inhibitor of neuronal NOS itself, and must first be de-estrified to N omega-nitro-L-arginine to potently inhibit this enzyme. Systemic (10 mg/kg) and icv (1 microgram) pretreatment with L-NNA enhanced more effectively the carbachol-induced rise in corticosterone secretion than did pretreatment with L-NAME by either route. These results are the first direct evidence that endogenous NO significantly inhibits the HPA response to central cholinergic, muscarinic receptor stimulation under in vivo conditions.
 ...
PMID:Mediation by nitric oxide of the carbachol-induced corticosterone secretion in rats. 922 31

Leptin, an adipocyte-derived 16 kDa polypeptide hormone, has been found to regulate food intake and thermogenesis by modulating stimulatory and inhibitory pathways in the feeding circuitry of the hypothalamus, among which corticotropin releasing hormone (CRH). Nitric oxide (NO) and prostaglandins have been shown to be involved in both CRH neurosecretion and feeding regulation. We have investigated the role of NO, prostaglandin E2 and prostaglandin F2alpha as mediators of the hypothalamic effects of leptin and their possible involvement in leptin-stimulated CRH secretion. Using primary cultures of neonatal (5- to 6-day-old) rat hypothalamic cells, we confirmed that leptin (0.1-10 nM) stimulates CRH secretion. This effect was not blocked by L-N(G)-nitro-methyl-arginine (L-NAME, 100 microM), a NO-synthase competitive inhibitor; and leptin did not stimulate NO production. Cyclooxygenase inhibition by indomethacin (10 microM) did not modify leptin-induced CRH secretion, while leptin stimulated prostaglandin E2, and prostaglandin F2alpha secretion. In conclusion, leptin-induced hypothalamic CRH secretion is not modulated by NO-synthase- or cyclooxygenase-mediated mechanisms; leptin does not stimulate NO production, but it stimulates prostaglandin E2 and F2alpha production, which could add to the growing list of mediators of leptin signaling in the hypothalamus.
 ...
PMID:Leptin stimulates prostaglandin E2 and F2alpha, but not nitric oxide production in neonatal rat hypothalamus. 1022 66

It has been shown that the hypothalamic-pituitary-adrenal (HPA) axis responses to immune-derived stimuli in particular can be modulated by nitric oxide (NO). In the present study we examined the effect of endogenous and exogenous NO on the HPA axis responses to neural stimuli which are not related to immune functions. Intracerebroventricular injection of NOR-3, a donor of NO, had no effect on basal HPA axis activity but significantly attenuated the secretion of median eminence (ME) CRH-41 as well as the serum ACTH and corticosterone (CS) in response to acute photic stimulation in a dose-dependent manner. Intracerebroventricular administration of N-omega-nitro-L-arginine methyl ester (L-NAME), a general NOS inhibitor, significantly enhanced ACTH and CS responses to this stress but did not change the basal levels of these hormones. On the other hand, i.c.v. injection of aminoguanidine, an inhibitor of inducible NO synthase (NOS) but not of neuronal NOS, did not affect the HPA axis responses to photic stimulation. These results suggest that: (1) NO is involved in modulation of the HPA axis responses to neural stimuli which are not dependent on immune factors, (2) the effect of NO is mediated by inhibition of hypothalamic ME CRH-41 secretion, and (3) this effect is probably mediated by neuronal NOS and not by inducible NOS.
 ...
PMID:Effect of exogenous nitric oxide and inhibitors of nitric oxide synthase on the hypothalamic pituitary adrenal axis responses to neural stimuli. 1051 77

In this study, using the human placenta perfused in vitro with Krebs' bicarbonate solution, we have examined the effects of changes in oxygen tension on the vasoreactivity of fetal placental blood vessels to corticotropin releasing hormone (CRH). Vasodilatory responses to human synthetic CRH were measured during sub-maximal vasoconstriction of the fetal placental circulation with prostaglandin F(2alpha)(PGF(2alpha)) (1-100 micrometer). Decreases in fetal placental arterial perfusion pressure (FAP) were obtained with CRH under conditions of high oxygen or low oxygen tension, >/=450 mmHg and </=50 mmHg, respectively. Secretion of CRH into the maternal and fetal placental circulations was measured during changes in oxygen tension in normal placentae and placentae from abnormal pregnancies complicated by pre-eclampsia. The change from high to low oxygen perfusion resulted in a small increase in the basal perfusion pressure (21+/-3.6 to 28.3+/-2.6 mmHg; (P</= 0.001, Student's paired t -test). During high oxygen perfusion, CRH (0. 3-3000 p m) caused a concentration dependent reduction of the PGF(2alpha)induced increase in FAP. However, during low oxygen perfusion, the vasodilatory effects of CRH were completely inhibited (P</= 0.05, regression analysis, ANOVA). The effect of the NO synthase inhibitor l -nitro-omega-arginine methyl ester (l -NAME, 1-100 micrometer), on basal FAP during high and low oxygen conditions was also established. Low oxygen perfusion significantly attenuated l -NAME-induced increases in perfusion pressure (P</= 0.05, regression analysis, ANOVA). Low oxygen perfusion was associated with an increase in CRH secretion into the maternal but not fetal circulation. CRH release into either the maternal or fetal circulations of abnormal placentae were not significantly different from normal controls. In conclusion CRH-induced vasodilatation of the fetal placental vasculature in vitro is inhibited during low oxygen perfusion. This effect may be related to reduced NO production. Reduced CRH induced vasodilation is associated with increased secretion of the CRH into the maternal but not fetal circulation.
 ...
PMID:Fetal placental vascular responses to corticotropin-releasing hormone in vitro. Effects of variation in oxygen tension. 1098 75

In vivo and in vitro electrophysiological experiments were performed on the rat dorsal vagal complex (DVC, i.e. nucleus of the tractus solitarius, NTS, and dorsal motor nucleus of the vagus, DMV) to examine the effects of corticotropin releasing hormone (CRF) on the central components of the vago-vagal reflex control of gastric function. When applied to gastrointestinal projecting DMV neurones, CRF (10-300 nM) induced a concentration-dependent membrane depolarization, an increase in action potential firing rate and decrease in amplitude of the action potential afterhyperpolarization (P < 0.05). Pretreatment with the non-selective CRF antagonist, astressin (0.5-1 microM) or the selective CRF(2) receptor antagonist, astressin 2B (500 nM) attenuated the CRF-induced increase in firing rate but did not alter basal discharge rate. CRF (30-300 nM) increased the amplitude of excitatory postsynaptic currents (EPSCs) evoked by stimulation of the NTS (P < 0.05). An alteration in the paired pulse ratio indicated the EPSC's increase occurred due to actions at presynaptic sites. In the in vivo anaesthetized rat preparation, bilateral microinjections (20 fmol in 20 nl for each site) of CRF in the DVC decreased gastric motility in rats pretreated with the muscarinic agonist, bethanecol (P < 0.05). The effects of CRF were abolished by systemic administration of the NOS inhibitor, L-NAME, or by bilateral vagotomy. We concluded that CRF had both a direct and an indirect excitatory effect on DMV neurones via activation of CRF(2) receptors and the decrease in gastric motility observed following microinjection of CRF in the DVC is due to the activation of an inhibitory non-adrenergic non-cholinergic input to the gastrointestinal tract.
 ...
PMID:In vitro and in vivo analysis of the effects of corticotropin releasing factor on rat dorsal vagal complex. 1218 Dec 86

We investigated the role of nitric oxide (NO) in the interleukin 1beta (IL-1beta) and nicotine induced hypothalamic-pituitary-adrenal axis (HPA) responses, and a possible significance of CRH and vasopressin in these responses under basal and social stress conditions. Male Wistar rats were crowded in cages for 7 days prior to treatment. All compounds were injected i.p., nitric oxide synthase (NOS) inhibitors, alpha-helical CRH antagonist and vasopressin receptor antagonist 15 min before IL-1beta or nicotine. Identical treatment received control non-stressed rats. Plasma ACTH and serum corticosterone levels were measured 1 h after IL-1beta or nicotine injection. L-NAME (2 mg/kg), a general nitric oxide synthase (NOS) inhibitor, considerably reduced the ACTH and corticosterone response to IL-1beta (0.5 microg/rat) the same extent in control and crowded rats. CRH antagonist almost abolished the nicotine-induced hormone responses and vasopressin antagonist reduced ACTH secretion. Constitutive endothelial eNOS and neuronal nNOS inhibitors substantially enhanced the nicotine-elicited ACTH and corticosterone response and inducible iNOS inhibitor, aminoguanidine, did not affect these responses in non-stressed rats. Social stress significantly attenuated the nicotine-induced ACTH and corticosterone response. In crowded rats L-NAME significantly deepened the stress-induced decrease in the nicotine-evoked ACTH and corticosterone response. In stressed rats neuronal NOS antagonist did not alter the nicotine-evoked hormone responses and inducible NOS inhibitor partly reversed the stress-induced decrease in ACTH response to nicotine. These results indicate that NO plays crucial role in the IL-1beta-induced HPA axis stimulation under basal and social stress conditions. CRH and vasopressin of the hypothalamic paraventricular nucleus may be involved in the nicotine induced alterations of HPA axis activity. NO generated by eNOS, but not nNOS, is involved in the stress-induced alterations of HPA axis activity by nicotine.
 ...
PMID:Nitric oxide mediates the interleukin-1beta- and nicotine-induced hypothalamic-pituitary-adrenocortical response during social stress. 1620 70

In this report we investigated the effect of 7-nitroindazole (7-NI), a specific neuronal inhibitor of nitric oxide synthase (nNOS) and L-NAME, a nonselective NOS inhibitor upon the adrenergic- and CRH-induced stimulation of the hypothalamic-pituitary-adrenal axis in nonanesthetized rats. 7-NI given i.p. and L-NAME administered i.c.v. considerably reduced ACTH and corticosterone secretion induced by phenylephrine (30 microg i.c.v.), an alpha(1)-adrenergic receptor agonist. These inhibitors also diminished the HPA response to isoprenaline (20 microg i.c.v.), a nonselective beta-adrenergic receptor agonist, and i.c.v. L-NAME significantly lowered the ACTH and corticosterone response to clenbuterol (10 microg i.c.v.), a selective beta(2)-adrenergic agonist. L-NAME abolished the noradrenaline (NA), an alpha- and beta-receptor agonist-evoked ACTH and corticosterone response, which was reversed by pretreatment with i.p. L-arginine, an endogenous NO substrate. 7-NI abolished the stimulatory action of corticotropin-releasing hormone (CRH 1 microg/kg i.p.) on ACTH but not corticosterone secretion. L-NAME only moderately diminished the CRH-induced ACTH secretion, suggesting that a major part of the CRH-induced HPA axis activation is of neuronal origin. Dihydropyridine, nifedipine, a specific L-type Ca(2+) channel blocker, inhibited significantly the CRH-induced ACTH and corticosterone response in rats exposed to 3 days crowding stress but not in rats under basal conditions. This finding indicates the strategic importance of Ca(2+) influx into the pituitary corticotrops to meet increased secretory requirement under stressful conditions. Collectively, our results point to complex functional relationship between NO, adrenergic agents CRH and Ca(2+) in the regulation of HPA axis activity.
 ...
PMID:Nitric oxide in the adrenergic-and CRH-induced activation of hypothalamic-pituitary-adrenal axis. 1862 51