Effects of corticosteroids and neurosteroids on sleep EEG.
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Adrenal Cortex Hormones↗
Biomedical subjects
R Rupprecht
Publications and source records attributed to R Rupprecht.
Identification and characterization of a 3',5'-cyclic adenosine monophosphate-responsive element in the human corticotropin-releasing hormone gene promoter.
The regulation of human corticotropin-releasing hormone (hCRH) gene promoter activity by inducers of cAMP was investigated by transient transfection with a construct containing the hCRH gene promoter fused to the chloramphenicol acetyltransferase gene. Expression of hCRH-chloramphenicol acetyltransferase was strongly enhanced by forskolin in the neuroblastoma SK-N-MC and choriocarcinoma JAR cell lines. Overexpression of the catalytic subunit of protein kinase A dispensed the need for forskolin, and cotransfection of cAMP-responsive element-binding protein cDNAs enhanced forskolin-dependent expression of the hCRH promoter. Progressive 5'-end deletions of the hCRH promoter delineated a cAMP- responsive region between -226 and -164 base pairs. This fragment contained the sequence TGACGTCA at -221 base pairs, consistent with the consensus motif for a CRE. A homologous oligonucleotide responded to cAMP when cloned in either orientation in front of the thymidine kinase promoter. However, the level of constitutive and inductive cAMP expression was dependent on the cell line and on intrinsic properties of the promoter. Mutation of the wild type CRH-CRE sequence into an AP-1 site (TGAGTCA) completely abolished stimulation by cAMP. In contrast, coexpression of the catalytic subunit of protein kinase A dispensed the need for stimulation with forskolin, which showed that the CRH-CRE oligonucleotide served as a functional equivalent of the native CRE element.
Base Sequence↗
Use of self-curing composite resins to facilitate amalgam repair.
Resin cements, which have been shown to adhere to various metal alloys, were investigated as possible repair adhesives for dental amalgam. Test bars of repaired amalgam, formed by condensing new alloy against previously set alloy with or without the use of "adhesive" resins, were subjected to three-point bending measurements of transverse fracture strength. The results indicated that application of adhesive resin did not improve the breaking strength of the repaired specimens from that of specimens prepared without the use of such resins. The breaking strength of all repaired specimens was approximately 15% of the transverse fracture strength of the original intact amalgam bars. Scanning electron microscopy revealed that there was an intermixing of fresh amalgam and unset interfacial resin, which led to mechanical bonding of these materials, but there was no evidence of adhesion of the resin to the previously set amalgam.
Acrylic Resins↗
Disturbed glucocorticoid receptor autoregulation and corticotropin response to dexamethasone in depressives pretreated with metyrapone.
We studied glucocorticoid receptor autoregulation and corticotropin response to dexamethasone in depressed patients and controls, attempting to control for the confounding effect of endogenous glucocorticoids. After depletion of endogenous cortisol, depressed patients showed an attenuated suppressibility of corticotropin by dexamethasone in the face of unchanged dexamethasone plasma levels. Beta-endorphin levels were strongly correlated with adrenocorticotropic hormone (ACTH) concentrations. Although metyrapone administration resulted in a marked rise of glucocorticoid receptor sites per cell in controls, this effect was not present in depressives. These data support the hypothesis of a decreased glucocorticoid receptor plasticity and a partial steroid resistance in depression.
Adolescent↗
In vivo and in vitro effects of glucocorticoids on lectin-induced blastogenesis in atopic dermatitis.
The effects of glucocorticoids administered in vivo and in vitro on lectin-induced proliferation of lymphocytes sampled from venous blood were investigated in patients with atopic dermatitis (AD) and in normal controls. Stimulation by concanavalin A (Con A), phytohaemagglutinin A (PHA) and pokeweed mitogen (PWM) in patients and controls did not differ significantly under baseline conditions. After in vivo administration of methylprednisolone the decline of Con A-induced blastogenesis of leucocytes was similar in both groups, whereas PHA stimulation caused a significant reduction in the controls only. In vitro addition of different dexamethasone concentrations had a pronounced suppressive effect on Con A- and PHA-induced blastogenesis in both groups, whereas PWM stimulation was unaffected. Pretreatment in vivo with methylprednisolone further decreased the suppression of the Con A and PHA lymphocyte proliferation rate by dexamethasone added in vitro in controls but not in patients. With regard to B-cell proliferation generated by PWM, no consistent glucocorticoid effect could be observed. The impaired effect on lymphocyte blastogenesis of glucocorticoids administered in vivo, in contrast to a normal in vitro reaction to dexamethasone, together with recent findings of an altered glucocorticoid receptor pharmacology in AD, points to a decreased biological in vivo efficiency of methylprednisolone in atopic dermatitis.
Adult↗
In vivo and in vitro effects of glucocorticoids on lymphocyte proliferation in depression.
Twelve severely depressed patients and 13 healthy controls were studied under baseline, metyrapone and metyrapone plus dexamethasone pretreated conditions. Lymphocyte proliferation data were obtained by concanavalin A, phytohaemagglutinin and pokeweed mitogen (PWM) stimulation. There was a decrease in PWM-induced B-cell proliferation and an increase in inhibition of spontaneous leucocyte proliferation by dexamethasone added in vitro following metyrapone administration in vivo, in healthy controls, which was not present in the depressed patients. These data support the concept of a decreased functional plasticity of the glucocorticoid receptor in depression also at the cellular level.
Adolescent↗
Normal lymphocyte responsiveness to lectins but impaired sensitivity to in vitro glucocorticoids in major depression.
The mitogen-induced lymphocyte proliferative response and its sensitivity to in vitro (10(-10)-10(-6) M) dexamethasone (DEX) administration were investigated in 12 severely depressed patients and 13 healthy controls. Patients with major depressive disorder exhibited no impairment of lectin-induced blastogenesis, but a significantly weaker suppressive effect of in vitro DEX on 1.0 microgram/ml phytohemagglutinin A-induced proliferation. The inhibitory potency of in vitro DEX was inversely correlated with in vivo adrenal cortical hormone levels at 4.00 p.m. These effects were not observed with pokeweed mitogen- and concanavalin A-stimulated cells. There were no correlations with age, weight, sex or severity of depression. These results do not support the hypothesis of a primarily impaired cell-mediated immunity, but might be indicative of reduced glucocorticoid receptor sensitivity in major depressive disorder.
Adrenocorticotropic Hormone↗
Elevated glucocorticoid receptor concentrations before and after glucocorticoid therapy in peripheral mononuclear leukocytes of patients with atopic dermatitis.
The number and affinity of glucocorticoid binding sites in peripheral mononuclear leukocytes of patients with atopic dermatitis (AD) and healthy controls were determined under baseline conditions and after a defined oral glucocorticoid treatment. Patients with AD (n = 15) exhibited significantly more glucocorticoid receptors (GR) per cell than the control group (n = 22), while the GR affinity did not differ. Methylprednisolone treatment resulted in a significant reduction of the GR sites per cell in the steroid-treated control group (n = 10) in contrast to the patients. The dissociation constant was not affected by methylprednisolone treatment in either group. In view of the therapeutic efficiency of glucocorticoids in AD and findings of abnormal cAMP and cAMP-phosphodiesterase activity, the elevated GR concentrations in AD lend support to the hypothesis of a compensatory GR upregulation due to an insufficient action of endogenous cortisol or to altered cAMP-induced GR expression.
3',5'-Cyclic-AMP Phosphodiesterases↗
Multihormonal response to dexamethasone. A study in atopic dermatitis and normal controls.
Although minor disturbances of the circadian serum cortisol rhythm and diminished excretion of steroid metabolites have been reported in patients with atopic dermatitis, test assays regarding subtle neuroendocrine alterations have not been employed so far. We therefore studied the serum concentrations of cortisol, prolactin and adrenocorticotropin under baseline conditions, after 1 mg dexamethasone and after a defined methylprednisolone treatment in 15 patients with atopic dermatitis, in comparison with 10 healthy controls. The assessment of the hormones revealed no remarkable differences between either group at any of the blood sampling time points. However, in 3 patients and 2 control subjects, though exhibiting no concomitant disease, we could find no suppression of endogenous cortisol to below 5 micrograms/dl after oral intake of 1 mg dexamethasone. These cortisol non-suppressors showed lower dexamethasone serum concentrations in the morning after its administration, as compared with the suppressors. Acute (1 mg dexamethasone) or prolonged (40 mg methylprednisolone over 6 days) intake of glucocorticoids suppressed prolactin levels in both groups, demonstrating that the effect of glucocorticoids on the hormone system is not restricted to the hypothalamic-pituitary-adrenal axis. Our results indicate an intact feedback response of this hormonal axis to 1 mg dexamethasone and the ability of long-term as well as acute glucocorticoid administration to influence the prolactin secretion in patients with atopic dermatitis.
Adolescent↗
The influence of dexamethasone on growth hormone (GH). Response to GH-releasing hormone in normal men.
There is evidence that glucocorticoids may have a bimodal effect on growth hormone release in vitro and in vivo. To explore the influence of a single low dose administration of dexamethasone on the hypothalamic-pituitary-somatotropic system, 11 male healthy subjects received 50 micrograms synthetic human GHRH-44 amide as an i.v. bolus dose with and without pretreatment with orally administered 1 mg dexamethasone 9 hours prior to GHRH stimulation. Dexamethasone preparation did affect neither baseline levels of GH and IGF-I nor GHRH induced GH secretory patterns assessed by delta max and by the net area under the response curves. These results add to previous reports that corticosteroids may have different effects on GH secretory dynamics dependent on dose and duration of application.
Adult↗
Glucocorticoid receptors on mononuclear leukocytes in Alzheimer's disease.
Several lines of evidence suggest disturbances of the hypothalamic-pituitary-adrenal (HPA) system in Alzheimer's disease (AD). In an exploration of the potential role of the glucocorticoid receptor (GR) in AD, GR density and affinity were assessed on mononuclear leukocytes of 12 AD patients and 12 healthy controls. GR binding characteristics did not differ between patients and controls or between patients subdivided according to diagnosis or associated clinical features. These data suggest that the abnormalities of the HPA system in AD are not related to a GR deficiency.
Adrenocorticotropic Hormone↗
Endocrine responses to growth hormone releasing hormone and corticotropin releasing hormone in early-onset Alzheimer's disease.
In a study of the hypothalamic-pituitary-somatotropic (HPS) and the hypothalamic-pituitary-adrenal (HPA) systems in early-onset Alzheimer's disease (AD), 10 drug-naive patients and matched controls were given 50 micrograms growth hormone releasing hormone (GHRH) at 9 a.m. and 100 micrograms corticotropin releasing hormone (CRH) at 6 p.m. as an i.v. bolus dose. Compared with controls, patients with AD showed attenuated GHRH-induced growth hormone (GH) responses and decreased adrenocorticotropic hormone (ACTH) but normal cortisol secretion following CRH. GH responses to GHRH were negatively correlated with the plasma insulin-like growth factor (IGF-I) concentrations and the severity of dementia. A positive correlation was found between GHRH-evoked GH release and ACTH responses to CRH. The results suggest a pathological process at the level of the pituitary or the hypothalamus, possibly involving a cholinergic, monoaminergic, or peptidergic imbalance in AD, and support the view that altered HPS and HPA secretory dynamics in AD are related to the underlying brain dysfunction.
Adrenocorticotropic Hormone↗
Corticotropin and cortisol secretion after central 5-hydroxytryptamine-1A (5-HT1A) receptor activation: effects of 5-HT receptor and beta-adrenoceptor antagonists.
To explore the involvement of 5-hydroxytryptamine-1A (5-HT1A) receptors in hypothalamic-pituitary-adrenal (HPA) axis regulation, various doses of ipsapirone (IPS), a centrally acting pyrimidinylpiperazine with considerable affinity and selectivity for 5-HT1A recognition sites, were administered to normal subjects. IPS dose-dependently increased plasma ACTH concentrations from -78 +/- 63 to 614 +/- 250 pmol.min/L (P less than 0.01) and plasma cortisol concentrations from -10.8 +/- 2.9 x 10(3) to 21.3 +/- 8.2 x 10(3) nmol.min/L (P less than 0.01) at a dose of 0.3 mg/kg in six men. The nonselective 5-HT receptor antagonist metergoline which acts at both 5-HT1 and 5-HT2 receptors partially blocked the HPA response to IPS in six women and three men. The mean maximal integrated ACTH response decreased from 746 +/- 297 to 40 +/- 146 pmol/min.L (P less than 0.05), and the increase in cortisol was attenuated from 22.9 +/- 9.9 x 10(3) to 11.9 +/- 6.3 x 10(3) nmol.min/L (P less than 0.05). The nonselective beta-adrenergic and selective 5-HT1A/1B receptor antagonist (+/-)pindolol was without effect on basal HPA activity, but completely antagonized the IPS-induced plasma ACTH and cortisol responses. The mean maximal integrated ACTH response decreased to 8.0 +/- 78 pmol.min/L (P less than 0.05), and the cortisol response was reduced to -2.3 +/- 6.5 x 10(3) nmol.min/L (P less than 0.05). The selective beta 1-adrenoceptor antagonist betaxolol did not significantly alter the IPS-induced HPA response.(ABSTRACT TRUNCATED AT 250 WORDS)
Adrenergic beta-Agonists↗
[Hormonal aspects of erectile dysfunction].
Organic erectile dysfunction may be due to vascular, local, neurogenic, or hormonal disturbances. Various ascertainments of basal levels of testosterone, prolactin, and other hormones produced inconsistent results, although hyperprolactinemia and hypogonadism have been shown to be associated with erectile dysfunction. Recent studies by means of the dexamethasone suppression test (DST) revealed not only clinical but also endocrinological connections between erectile dysfunction and depression. These results suggest possible multiendocrinological alterations in some of the patients suffering from erectile dysfunction, similar to those obtained in depressive disorders.
Depressive Disorder↗
Comparison of GH responses after human GHRH-44 amide administration and TRH-induced TSH release in depressed patients.
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Adult↗
Psychoneuroendocrine research in depression. I. Hormone levels of different neuroendocrine axes and the dexamethasone suppression test.
Psychoneuroendocrinology is of major importance in the biological research of depression. Most studies have focussed on the regulation of the hypothalamic-pituitary-adrenal (HPA) axis but other endocrine systems such as the hypothalamic-pituitary-thyroid (HPT), hypothalamic-pituitary-somatotropic (HPS), and the hypothalamic-pituitary-gonadal (HPG) axis have also been shown to be involved in the psychobiology of depression. There are close interrelations between various endocrine axes which possibly are affected during depressive illness. A variety of neuroendocrine abnormalities has been detected in depressive disorder but the pathophysiology of these derangements remains still unclear. Although the currently used neuroendocrine tests are not of diagnostic validity they may help to clarify the pathophysiological significance of the complex regulatory mechanisms of different neuroendocrine axes in affective disorders. Neuroendocrine regulation is determined both by peripheral and central mechanisms which both have to be adequately considered as well as potent interactions between various endocrine systems in further neuroendocrine depression research.
Adrenocorticotropic Hormone↗
Psychoneuroendocrine research in depression. II. Hormonal responses to releasing hormones as a probe for hypothalamic-pituitary-endorgan dysfunction.
The rapid growth of fundamental research in neuroendocrinology includes advances in our understanding of the role of neurotransmitters in the control of hypophysiotropic neurons, the concept of neurosecretion, the portal circulation chemotransmitter hypothesis of anterior pituitary regulation, and the chemical structures of the hypophysiotropic hormones. These advances correspond to the emergence of psychoneurobiology, with the appreciation of the roles of neuropeptides, such as hypothalamic releasing and inhibiting hormones, their relevance to brain function and possible involvement in psychiatric disease, and their introduction into psychoneuroendocrinological studies. The subject of the present review is to summarize and integrate current knowledge of the neuroendocrinology of hypothalamic releasing and inhibiting hormones, to apply it to the understanding of the pathogenesis of depression, and to evaluate their relevance as psychoneuroendocrine research tools.
Corticotropin-Releasing Hormone↗
The influence of human corticotropin-releasing hormone on somatostatin secretion in depressed patients and controls.
Twenty subjects (10 patients with a major depressive episode and 10 individually matched healthy controls) received 100 micrograms synthetic human corticotropin-releasing hormone (hCRH) as an i.v. bolus dose. Healthy subjects and depressed patients exhibited a significant increase of plasma somatostatin (SRIH) concentrations with no difference between both comparison groups. Compared to controls, depressed patients showed a significant attenuation of corticotropin (ACTH) responses, while cortisol secretion in response to hCRH was normal. No correlations were found among basal plasma concentrations of SRIH, ACTH or cortisol and SRIH, ACTH or cortisol responses following hCRH. These findings are compatible with the hypothesis that hypothalamic-pituitary-adrenal (HPA) hyperactivity in the depressive state may primarily be due to central hypersecretion of CRH and support the view of a hCRH-induced SRIH secretion which is not related to HPA dysfunction associated with major depression.
Adrenocorticotropic Hormone↗