Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01189 (beta-endorphin)
 21,003 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Stress-induced corticosterone (CORT) secretion that causes a rapid blockade of courtship clasping by male roughskin newts (Taricha granulosa) is mediated by a specific neuronal membrane receptor for CORT. Amplectic clasping, which can be triggered by pressure on the ventral body surface and cloaca, is controlled by the influence of medullary neurons on the spinal cord. Using clasping as a simple neurobehavioral model, we have focused our analysis of CORT effects on clasping by examining the steroid's effects on neurophysiological properties of medullary neurons, especially medullary reticulospinal neurons, the principal output cells from the brain to the spinal cord. Systemic CORT caused, within 3 min of injection, diverse reductions in reticulospinal neuron excitability. Another rapid CORT effect on medullary neurons was to depress responsiveness to pressure on the cloaca. Experiments with chronically implanted, freely moving newts revealed that the rapid CORT effects are quite specific to neural processes related to clasping. CORT injections rapidly blocked clasping in response to cloacal stimuli and concurrently depressed neuronal responses to cloacal pressure and firing associated with clasping. Activity of reticulospinal neurons was often associated with nonclasping movements and this activity was rarely altered by CORT. Thus, CORT mainly affected aspects of neuronal function related to clasping. In other neurophysiological experiments, we found that the neuropeptides vasotocin and corticotropin-releasing hormone modified the neural effects of CORT. Prior exposure of medullary neurons to either of these neuropeptides caused systemic CORT administration to rapidly potentiate neuronal responses to cloacal stimuli, indicating that the direction and potency of CORT effects depend critically on the prevailing neuroendocrine state of the brain.
Steroids
PMID:A neurobehavioral model for rapid actions of corticosterone on sensorimotor integration. 1032 77

Polyclonal antiserum against 3beta,17alpha-dihydroxypregn-5-en-20-one-19-O-(carboxymethyl )-oxime bovine serum albumin (17alpha-hydroxypregnenolone-19-CMO:BSA), was raised in rabbits. Its main structural determinants were the substituents on D-ring as demonstrated by its 107% cross-reaction with 17alpha-hydroxyprogesterone. This unspecificity was almost completely eliminated by addition of the excess of the cross-reactant directly to the analytical system. The contribution of the cross-reactant from the sample in such a system became negligible due to saturation of the populations of polyclonal antibodies recognizing the analyte as well as the cross-reactant. The possible interference of 17alpha-hydroxypregnenolone-3-sulfate was avoided by inserting ether extraction. The analytical system appeared to be stable to differences in cross-reactant concentrations even in samples from patients with pathologically elevated serum levels of 17alpha-hydroxyprogesterone. The radioimmunoassay was compared with the system using the unspecific antiserum alone, but after separation of the cross-reactants by HPLC. As demonstrated by parallel measurement of 125 samples of human plasma from both sexes and various ages either before and/or after adrenocorticotropin stimulation and 17 samples with elevated basal of human plasma 17alpha-hydroxyprogesterone levels, an excellent correlation was achieved between both methods. The method, based on a simple addition of the cross-reactant, avoids the time-consuming chromatographic separation and, in comparison with the other approaches for improving the specificity of polyclonal antisera, is efficient and rapid. Mathematical analysis of the relations in equilibrium demonstrates that such a simple approach is an efficient way for improvement of immunoassay specificity using some polyclonal antisera.
Steroids 1999 May
PMID:Elimination of cross-reactivity by addition of an excess of cross-reactant for radioimmunoassay of 17alpha-hydroxypregnenolone. 1040 84

In the corticotroph-like murine pituitary tumor cell line, AtT-20, adrenocorticotropic hormone release is triggered by corticotropin-releasing hormone and is attenuated by the synthetic adrenal steroid dexamethasone. The precise mechanisms by which dexamethasone inhibits secretion are under investigation. We examined whether dexamethasone can modulate release via regulation of calcium homeostasis. More specifically, we have evaluated the effects of dexamethasone on calcium current, intracellular calcium concentration, and adrenocorticotropic hormone release. Using perforated patch-clamp and calcium imaging with fura PE3/AM, we found that dexamethasone decreases calcium current and intracellular calcium levels. The inhibition of current by dexamethasone is not, however, altered by the calcium channel antagonists nifedipine (L-type) or omega-agatoxin IVA (P/Q-type), despite the presence of these calcium channel subtypes in AtT-20 cells and the exclusive coupling of adrenocorticotropic hormone release to the L-type channel in these cells. We also evaluated the temporal relationship between dexamethasone-mediated inhibition of secretion and calcium influx. Whereas a prolonged (2 h) incubation with dexamethasone inhibits corticotropin-induced release by approximately 40%, a rapid (10 min) incubation (a time interval sufficient for dexamethasone-mediated inhibition of calcium transients) does not inhibit release. These data suggest, therefore, that dexamethasone does, indeed, modulate calcium homeostasis in AtT-20 cells, but that this effect is not responsible for its inhibition of secretion.
Steroids 1999 Jun
PMID:Dexamethasone-mediated inhibition of calcium transients and ACTH release in a pituitary cell line (AtT-20). 1043 77

Dehydroepiandrosterone (DHEA) is produced in prodigious quantities by the human adrenal, principally as the 3-sulfoconjugate DHEA sulfate (DS) during intrauterine life. The fetal zone and neocortex cells of the fetal adrenal express large amounts of DHEA sulfotransferase and minimal amounts, at least until very near the end of gestation, of 3beta-hydroxysteroid dehydrogenase. This pattern of enzyme expression favors substantial secretion of DHEA/DS with minimal cortisol produced; the DHEA/DS serves as the major precursor for placental estrogen formation in human pregnancy. Aside from adrenocorticotropin, other physiologic regulators of growth and steroidogenesis in the fetal adrenal have been postulated to exist, but have yet to be identified. Whereas intrauterine stressors may activate adrenal cortisol secretion, the fetal adrenal responds to many pregnancy conditions by suppressing DHEA/DS formation. After birth, the human adrenal undergoes reorganization whereby the large, inner fetal zone regresses, and DHEA/DS production is diminished. Just prior to gonadal maturation, the human adrenal undergoes morphologic and functional changes (adrenarche) that give rise to a prominent zona reticularis that is characterized by the presence of DHEA sulfotransferase, the absence of 3beta-hydroxysteroid dehydrogenase, and an enhancement of DHEA/DS production. The adrenal of the adult responds to stress in many instances like that of the fetus: increased cortisol secretion and diminished DHEA/DS secretion. The mechanisms for this divergence in the adrenocortical pathway is unknown. With aging, there is suppression of DHEA/DS secretion, possibly as the consequence of an involution of the zona reticularis, but corticosteroid production continues unabated.
Steroids 1999 Sep
PMID:Dehydroepiandrosterone and dehydroepiandrosterone sulfate production in the human adrenal during development and aging. 1050 22

The understanding of epilepsy has advanced substantially in the past decade, and new anticonvulsant drugs with novel mechanisms of action are continually being developed. Some of these newer (and older) medications have been discussed in this article. A wide variety of other drugs is occasionally used in the management of epilepsy. Although parenteral magnesium sulfate is used mainly for the prevention and control of seizures in severe preeclampsia or eclampsia, parenteral magnesium sulfate may also be useful in controlling epileptic seizures associated with low plasma magnesium concentrations. Although considered obsolete, bromides have been useful in the management of tonic-clonic or myoclonic seizures in some infants and preadolescent children when other drugs were unsuitable. Acetazolamide may be useful in the management of refractory partial, myoclonic, absence or primary generalized tonic-clonic seizures; however, tolerance develops to the effect of the drug. Corticotropin and corticosteroids are sometimes used in the management of myoclonic seizures in infants. Steroids may be used in seizures due to intracerebral malignancies and metastasis but are more effective in blunting the intracranial swelling associated with these diseases. Recognition of these new drugs may allow the paramedic or EMT to identify seizure patients in the field. Knowledge of the side effects of these medications may be used to guide patients into appropriate treatment pathways.
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PMID:Anticonvulsant medications. 1145 38

Here we report on the progress we have made in elucidating the mechanisms through which estrogen alters synaptic responses in hypothalamic neurons. We examined the modulation by estrogen of the coupling of various receptor systems to inwardly rectifying and small conductance, Ca(2+)-activated K(+) (SK) channels. We used intracellular sharp-electrode and whole-cell recordings in hypothalamic slices from ovariectomized female guinea pigs. Estrogen rapidly uncouples mu-opioid receptors from G protein-gated inwardly rectifying K(+) (GIRK) channels in beta-endorphin neurons, manifest by a reduction in the potency of mu-opioid receptor agonists to hyperpolarize these cells. This effect is blocked by inhibitors of protein kinase A and protein kinase C. Estrogen also uncouples gamma-aminobutyric acid (GABA)(B) receptors from the same population of GIRK channels coupled to mu-opioid receptors. At 24 h after steroid administration, the GABA(B)/GIRK channel uncoupling observed in GABAergic neurons of the preoptic area (POA) is associated with reduced agonist efficacy. Conversely, estrogen enhances the efficacy of alpha(1)-adrenergic receptor agonists to inhibit apamin-sensitive SK currents in these POA GABAergic neurons, and does so in both a rapid and sustained fashion. Finally, we observed a direct, steroid-induced hyperpolarization of both arcuate and POA neurons, among which gonadotropin-releasing hormone (GnRH) neurons are particularly sensitive. These findings indicate a richly complex yet coordinated steroid modulation of K(+) channel activity that serves to control the excitability of hypothalamic neurons involved in regulating the reproductive axis.
Steroids 2002 May
PMID:Estrogen modulation of K(+) channel activity in hypothalamic neurons involved in the control of the reproductive axis. 1196 Jun 20

The efficacy of ACTH, particularly in high doses, for rapid and complete elimination of infantile spasms (IS) has been demonstrated in prospective controlled studies. However, the mechanisms for this efficacy remain unknown. ACTH promotes the release of adrenal steroids (glucocorticoids), and most ACTH effects on the central nervous system have been attributed to activation of glucocorticoid receptors. The manner in which activation of these receptors improves IS and the basis for the enhanced therapeutic effects of ACTH--compared with steroids--for this disorder are the focus of this chapter. First, a possible "common excitatory pathway," which is consistent with the many etiologies of IS and explains the confinement of this disorder to infancy, is proposed. This notion is based on the fact that all of the entities provoking IS activate the native "stress system" of the brain. This involves increased synthesis and release of the stress-activated neuropeptide, corticotropin-releasing hormone (CRH), in limbic, seizure-prone brain regions. CRH causes severe seizures in developing experimental animals, as well as limbic neuronal injury. Steroids, given as therapy or secreted from the adrenal gland upon treatment with ACTH, decrease the production and release of CRH in certain brain regions. Second, the hypothesis that ACTH directly influences limbic neurons via the recently characterized melanocortin receptors is considered, focusing on the effects of ACTH on the expression of CRH. Experimental data showing that ACTH potently reduces CRH expression in amygdala neurons is presented. This downregulation was not abolished by experimental elimination of steroids or by blocking their receptors and was reproduced by a centrally administered ACTH fragment that does not promote steroid release. Importantly, selective blocking of melanocortin receptors prevented ACTH-induced downregulation of CRH expression, providing direct evidence for the involvement of these receptors in the mechanisms by which ACTH exerts this effect. Thus, ACTH may reduce neuronal excitability in IS by two mechanisms of action: (1) by inducing steroid release and (2) by a direct, steroid-independent action on melanocortin receptors. These combined effects may explain the robust established clinical effects of ACTH in the therapy of IS.
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PMID:ACTH treatment of infantile spasms: mechanisms of its effects in modulation of neuronal excitability. 1204 Aug 92

It is known that the stress hyporesponsive period (SHRP), which seems to be related to an immature hypothalamo-pituitary-adrenal (HPA) regulatory system, occurs during the first 2 weeks after birth in rats. In the present study, we investigated the effects of sex-steroid hormones on adrenocortical responsiveness to adrenocorticotropic hormone (ACTH) in neonatal rats. The levels of cyclic adenosine 3',5'-monophosphate (cAMP), corticosterone, and adenylate cyclase activity increased with the dose of ACTH in adrenal cells of males and females in vitro. The ACTH responsiveness in adrenal cells increased with age (7-35 days of age), that is, the loss in responsiveness to ACTH just after birth began to recover in 14-35-day-old rats, but the responsiveness in 14-day-old rats was attenuated in males compared with females. Although castration markedly augmented the responsiveness in male rats, testosterone-replacement in the castrated male rats inhibited the enhancement. Furthermore, the responsiveness in 14-day-intact female rats was suppressed by treatment with testosterone. Expression levels of ACTH receptor mRNA in adrenals increased with age in the female rat, but not in the male. Castration enhanced the level of ACTH receptor mRNA to three-fold of that in intact male rats at 14 days of age, but replacement treatment with testosterone in castrated male rats lowered the elevated levels. Testicular androgens are thought to evoke a gender-specific response in neonates, and the temporal decrease of adrenal ACTH-responsiveness might be due to the topically immature adrenal system as well as the central nervous system in mammals.
Steroids 2003 May
PMID:Sex-differences in adrenocortical responsiveness during development in rats. 1279 94

Aim of the present study was to investigate the influence of hydrocortisone on muscle sympathetic nerve activity (MSNA) and hemodynamic parameters during different sympathoexcitatory manoeuvres in humans. The study focuses on the interaction of the hypothalamo-pituitary-adrenal system and the sympathetic nervous system. Hydrocortisone 100 mg or placebo was administered intravenously to eight young healthy subjects in a double-blind crossover design. After 6 h, blood pressure, heart rate and MSNA from the peroneal nerve were recorded at rest, during an arithmetic stress task, an apnea and a cold pressor test. Hydrocortisone treatment increased serum cortisol levels to the upper physiological range and suppressed basal levels of adrenocorticotropin. During mental stress, MSNA, heart rate and blood pressure levels were elevated independently of hydrocortisone pre-treatment. However, hydrocortisone induced a sustained increase in basal heart rate throughout the whole experiment. A stronger increase in diastolic blood pressure was observed during apnea and cold pressor test in the hydrocortisone experiments. MSNA or plasma catecholamines at rest or during the manoeuvres were not affected by hydrocortisone. The observed hydrocortisone effects may be due to an increased responsiveness of adrenergic receptors towards catecholamines or a central modulation of the baroreflex involving parasympathetic mechanisms. Further studies are needed to confirm that the increase in MSNA during mental stress does not depend on a concomitant activation of the hypothalamo-pituitary-adrenal system.
Steroids 2006 Mar
PMID:Differential effects of hydrocortisone on sympathetic and hemodynamic responses to sympathoexcitatory manoeuvres in men. 1638 32

Acute hypercytokinaemia represents an imbalance of pro-inflammatory and anti-inflammatory cytokines, and is believed to be responsible for the development of acute respiratory distress syndrome and multiple organ failure in severe cases of avian (H5N1) influenza. Although neuraminidase inhibitors are effective in treating avian influenza, especially if given within 48 h of infection, it is harder to prevent the resultant hypercytokinaemia from developing if the patient does not seek timely medical assistance. Steroids have been used for many decades in a wide variety of inflammatory conditions in which hypercytokinaemia plays a role, such as sepsis and viral infections, including severe acquired respiratory syndromes and avian influenza. However, to date, the results have been mixed. Part of the reason for the discrepancies might be the lack of understanding that low doses are required to prevent mortality in cases of adrenal insufficiency. Adrenal insufficiency, as defined in the sepsis/shock literature, is a plasma cortisol rise of at least 9 microg dl(-1) following a 250 microg dose of adrenocorticotropin hormone (ACTH), or reaching a plasma cortisol concentration of >25 microg dl(-1) following a 1-2 microg dose of ACTH. In addition, in the case of hypercytokinaemia induced by potent viruses, such as H5N1, systemic inflammation-induced, acquired glucocorticoid resistance is likely to be present. Adrenal insufficiency can be overcome, however, with prolonged (7-10 or more days) supraphysiological steroid treatment at a sufficiently high dose to address the excess activation of NF-kappaB, but low enough to avoid immune suppression. This is a much lower dose than has been typically used to treat avian influenza patients. Although steroids cannot be used as a monotherapy in the treatment of avian influenza, there might be a potential role for their use as an adjunct treatment to antiviral therapy if appropriate dosages can be determined. In this paper, likely mechanisms of adrenal insufficiency are discussed, drawing from a broad background of literature sources.
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PMID:A rationale for using steroids in the treatment of severe cases of H5N1 avian influenza. 1757 50


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