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)

Corticotropin-releasing hormone (CRH) is believed to have a role as an important brain neuroregulator acting through specific receptors coupled to adenylate cyclase in addition to its major role in regulating pituitary adrenocorticotropin synthesis and secretion. To study the potential modulatory effects of various regulators and the central effects of CRH, we studied the effects of phorbol ester myristate acetate (PMA), arginine vasopressin (AVP), corticosterone, dexamethasone, and progesterone on CRH stimulation of cyclic adenosine monophosphate (cAMP) production in extrahypothalamic forebrain cell cultures derived from day 17 gestation fetal rats. These cultures contain CRH receptors with similar characteristics as those in anterior pituitary and brain. CRH (10(-9) - 10(-7) M) stimulated cAMP in a dose-dependent fashion and maximal stimulation was clearly seen at 10(-7) M CRH. Incubation of the cells with PMA (10(-7) M), a protein kinase C (PKC) agonist, had no effect on basal cAMP, but potentiated CRH-stimulated cAMP. AVP (10(-8), 10(-7) M) had no effect on basal nor CRH-stimulated cAMP accumulation. Corticosterone (10(-7), 10(-6) M) or dexamethasone (10(-9) - 10(-7) M) pre-incubation for 18 h did not diminish basal cAMP levels nor inhibit CRH-induced stimulation of cAMP. However, corticosterone inhibited CRH-induced cAMP production in anterior pituitary cells. Neither did exposure to progesterone (2 x 10(-8) M) modulate basal cAMP, CRH-induced cAMP production nor the potentiation of CRH stimulation by PMA. The data demonstrate that CRH receptors in dissociated fetal extrahypothalamic forebrain cell cultures are coupled to an adenylyl cyclase/cAMP second messenger system similarly as shown in studies with anterior pituitary membranes.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Modulation of corticotropin-releasing hormone stimulated cyclic adenosine monophosphate production by brain cells. 762 Aug 89

1. We have determined in adrenalectomized male rats the effects of clamping plasma corticosterone and aldosterone at various concentrations on corticotropin-releasing hormone (CRH), neurotensin/neuromedin N (NT/N) and proenkephalin (pENK) mRNAs in the hypothalamus and amygdala using semi-quantitative in situ hybridization. 2. Corticosterone differentially regulated the levels of CRH and NT/N but not pENK mRNA. These effects were cell specific. CRH mRNA was reduced in the hypothalamic paraventricular nucleus (PVH), but increased in the central nucleus of the amygdala and bed nuclei of the stria terminalis. NT/N mRNA was never seen in the PVH, whereas levels increased in the central nucleus of the amygdala, but were unaffected in the lateral hypothalamic area. In those regions expressing pENK mRNA, levels were unaffected in all treatment groups. 3. CRH mRNA in both the central nucleus of the amygdala and PVH, and NT/N mRNA in the central nucleus of the amygdala were most sensitive to plasma corticosterone concentrations of less than 120 ng ml-1, i.e. those seen away from the peak of the diurnal rhythm. In adrenalectomized animals CRH mRNA in both the central nucleus of the amygdala and PVH could be set at levels usually seen in intact animals by the same plasma concentration of corticosterone. 4. The levels of CRH mRNA in the PVH and the central nucleus of the amygdala were closely correlated, while CRH and NT/N mRNA levels were similarly correlated in the central nucleus of the amygdala suggesting the existence of a common regulatory mechanism. The ED50 of their responses to corticosterone and correlations with thymus weight suggested the operation of glucocorticoid (type II) receptor mechanisms. 5. In the absence of corticosterone, aldosterone increased CRH and NT/N mRNA accumulation in the central nucleus of the amygdala, and increased CRH but not NT/N mRNA accumulation in the PVH. Aldosterone also blunted the dose-response effects of corticosterone on CRH and NT/N mRNA levels in the central nucleus of the amygdala, but not in the PVH. 6. These results suggest that, in intact animals, adrenal steroids play a major role in maintaining the levels of neuropeptide mRNAs in the PVH, bed nuclei of the stria terminalis and central nucleus of the amygdala. The results underscore the importance of cell-specific mechanisms operating to regulate the expression of neuropeptide genes in different cell types in response to diverse physiological conditions.
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PMID:Region-specific regulation of neuropeptide mRNAs in rat limbic forebrain neurones by aldosterone and corticosterone. 762 87

Glucocorticoids and stress are known to influence the synthesis of corticotropin-releasing hormone (CRH) at a variety of sites in brain, including the hypothalamus and amygdala. The recent cloning of the CRH receptor (CRH-R) enabled us to determine whether glucocorticoids or stress influenced CRH action via regulation of CRH-R. We, therefore, used in situ hybridization to measure CRH-R messenger RNA (mRNA) levels in the hypothalamic paraventricular nucleus (PVN), anterior pituitary (AP), amygdala, and bed nucleus of the stria terminalis (BNST) under several conditions. Systemic corticosterone (CORT) treatment, both daily injection (5 mg/rat.day) up to 14 days and pellet implant (200 mg) for 14 days, decreased CRH-R mRNA in the PVN and lateral and basolateral nucleus of the amygdala (BLA). Corticosterone injection (10 mg/rat.day, for 7 days) decreased CRH-R mRNA in the AP. Adrenalectomy also decreased CRH-R mRNA in the PVN and AP, but did not alter it in the BLA. In both sham and adrenalectomized rats with CORT pellet replacement (39 mg; ADX+CORT rats), acute (2-h) and repeated (2 h daily for 14 days) immobilization stress (which produced a large increase in plasma CORT in sham rats) increased CRH-R mRNA in the PVN and decreased it in the AP, but did not affect CRH-R mRNA in the BLA. However, ADX+CORT rats consistently had higher levels of CRH-R mRNA in both the PVN and AP than sham rats after stress. Brain stem hemisection, which damaged all ascending catecholaminergic fibers with the exception of the locus ceruleus, attenuated immobilization stress-induced up-regulation of CRH-R mRNA ipsilaterally in the PVN. None of the treatments affected CRH-R mRNA levels in the central and medial nucleus of the amygdala or the BNST. These results suggest that high concentrations of CORT or CRH synergistically decrease CRH-R mRNA levels in the AP, and that at least high CORT has an inhibitory effect on PVN CRH-R mRNA levels. However, stress input can override such inhibitory effects and thus up-regulate CRH-R mRNA in the PVN. The extrahypothalamic regions, such as amygdala and BNST may have different sensitivities to CORT or CRH for the regulation of CRH-R mRNA.
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PMID:Regulation of corticotropin-releasing hormone receptor messenger ribonucleic acid in the rat brain and pituitary by glucocorticoids and stress. 766 72

This investigation was carried out to determine the effects of bursectomy on in vitro response of adrenal glands to adrenocorticotropic hormone (ACTH) and testes to human chorionic gonadotropin (HCG) in immature male chickens. One-day-old Single Comb White Leghorn male chicks were surgically bursectomized (BSX). Sham-operated (sham) chicks were used as controls. At 5 wk of age, adrenal cortical cells (ACC) from BSX and sham birds were incubated in vitro with various concentrations (0, 10(-7), 10(-6), and 10(-5) M) of ACTH for 2 h, and then corticosterone was measured in all supernatants. At 15 wk of age, Leydig cells from testes of both groups were incubated in vitro with HCG (3,000 IU/mL) for 3 h, and then testosterone was measured in all supernatants. Corticosterone concentrations in response to both 10(-6) and 10(-5) ACTH were significantly lower for BSX than for sham ACC. Leydig cells from sham birds produced significantly more testosterone than those of BSX birds whether or not the cells were stimulated with HCG. Furthermore, Leydig cells from sham birds, but not from BSX birds, produced significantly more testosterone when stimulated with HCG than when saline was added. These results indicated that the bursa of Fabricius or its products might have a stimulatory effect on the response of ACC and Leydig cells to ACTH and HCG, respectively.
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PMID:Bursectomy and in vitro response of adrenal gland to adrenocorticotropic hormone and testis to human chorionic gonadotropin in immature male chickens. 816 56

The effects of acute treatment (i.p.) with selenium (Se) on glucoregulation, by measuring plasma levels of adrenocorticotropic hormone (ACTH), beta-endorphin (beta-EN), corticosterone (CORT) and glucose over time, were investigated. The hormones of the hypothalamic-pituitary adrenal (HPA) axis, were measured after treating rats with saline, Se: 1.6 mg/kg, or 3.8 mg/kg. Blood samples were collected before, 30, 60 and 90 min following injection. The results show that i.p. administration of Se (both doses) induce a rise in plasma ACTH, and beta-EN (P < 0.01). Plasma CORT and glucose levels also rose sharply by 30 min (P < 0.05). Corticosterone levels were increased in a dose-dependent fashion over the ensuing hour. Bilateral adrenal demedullation resulted in the abolishment of the Se-induced rise in plasma glucose. Pretreatment with metyrapone (300 mg/kg) was found to delay the Se-induced rise in plasma glucose. The results indicate that after a Se challenge the HPA axis is activated. In addition, CORT was found to be essential in the Se-induced rise in plasma glucose.
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PMID:Effect of selenium (Se) on plasma ACTH, beta-endorphin, corticosterone and glucose in rat: influence of adrenal enucleation and metyrapone pretreatment. 838 2

The article reviews some of the recent work showing how physiological stimuli act to alter neuropeptide gene expression. It describes how neural and humoral factors activated by physiological stimuli interact with the mechanisms regulating neuropeptide gene expression in neurons with either vascular (neurosecretory) or cellular (centrally directed) synapses. Although the focus will be on corticotropin-releasing hormone (CRH) in the hypothalamic paraventricular nucleus, comparisons will be made between this neurosecretory cell group and others that express this gene. The regulation of neuropeptide genes colocalized in neurons that synthesize CRH is also considered. The review begins with a brief historical introduction, placing peptides in the overall functional perspective of neurosecretory and centrally directed neurons. It then describes studies using in vitro preparations that reveal details of the signal transduction mechanisms responsible for altering the expression of neuropeptide genes. For the CRH gene they are providing the foundations for future work on how physiological stimuli alter mRNA levels in the whole animal. Physiological stimuli provide a very broad range of signals to neuropeptide neurons commensurate with the wide variety of motor responses they initiate. One important humoral signal impacting neuropeptide neurons is plasma corticosterone, and many workers have addressed this aspect of its function. Corticosterone appears capable of interacting with at least two different neuronal mechanisms to regulate CRH mRNA levels: one is clearly seen in paraventricular neurosecretory neurons, where increasing plasma corticosteroid reduces CRH mRNA levels; the other, seen in neurons in the central nucleus of the amygdala, acts to increase them. Since physiological stimuli present a complex mixture of humoral and neural signals to the CNS, integration of these two signal types is a critical aspect of peptide metabolism that requires detailed attention. Studies that are beginning to address this important question are described. Circadian influences play an important role in organizing homeostatic processes, and their influence on CRH gene expression is considered. The viscerosensory-motor integration associated with dehydration offers a useful model for investigating the role of peptides in neuronal function and motor architecture. Much of our work has concentrated on how peptide genes are regulated by alterations to fluid homeostasis, and these studies, along with those of other investigators, are described in this integrative context. Finally, consideration is given to the many studies that have addressed the impact of nonviscerosensory stimulation on neuropeptide gene expression.
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PMID:The impact of physiological stimuli on the expression of corticotropin-releasing hormone (CRH) and other neuropeptide genes. 881 98

We investigated the ability of various melanocortin peptides and corticosterone to influence habituation of prey-catching behavior in the toad, Bufo cognatus. Male toads were injected with various melanocortin peptide fragments or corticosterone 30 min prior to acquisition. Adrenocorticotropin (ACTH[1-39]), ACTH[4-10], and N-acetyl ACTH[1-13] amide (alpha-MSH) significantly decreased the number of turning reactions during acquisition in relation to controls. The effects of the noncorticotropic ACTH fragments were rapid and transient, occurring within the first 20 min of acquisition. Corticosterone caused a slight but significant decrease in the number of turning reactions. Neither des-acetyl alpha-MSH nor (Nle4, D-Phe7) alpha-MSH had any effect on acquisition. ACTH[1-39] was the only peptide that delayed extinction. The ability of alpha-MSH to facilitate acquisition was not observed in the presence of the alpha-MSH antagonist U-76188E. These data suggest that the effects of ACTH on habituation are, in part, independent of effects on glucocorticoid secretion. Apparently, similar structural requirements are necessary for the behavioral effects of melanocortins in amphibians and mammals.
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PMID:The effects of melanocortin peptides and corticosterone on habituation in the great plains toad, Bufo cognatus. 891 79

The subcutaneous injection of 5'-bromo-2' deoxyuridine (BrdU) was found to raise the plasma concentrations of ACTH, aldosterone and corticosterone in rats. The aldosterone response was observed at a lower dose of BrdU and lasted for a longer period than those of ACTH and corticosterone (1.25 versus 2.50 mg/100 g body weight; 48 versus 24 h). Corticosterone response to BrdU was partially reversed by the ACTH-receptor antagonist corticotropin-inhibiting peptide (CIP), and aldosterone response by the arginine vasopressin (AVP) V1-receptor antagonist [amino-Pen1, Val4,D-Arg8]-vasopressin (AVP-A). The angiotensin-II (ANG-II)-receptor antagonist [Sar1, Val5, Ala8]-ANG-II (SAR) was ineffective. CIP, AVP-A and SAR, when administered alone, did not alter basal levels of ACTH, aldosterone and corticosterone. In light of these findings the following conclusions can be drawn: (i) BrdU stimulates the hypothalamo-pituitary-adrenal axis in rats, and this effect may influence the results of cell-kinetics studies carried out with the BrdU-labelling technique, especially in those tissue that are highly responsive to glucocorticoids (e.g. pituitary, adrenal and lymphatic tissues); and (ii) different mechanisms underlie the aldosterone and corticosterone secretagogue effects of BrdU, the former being at least in part dependent on the stimulation of AVP release and the latter on the rise in ACTH secretion.
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PMID:Different mechanisms mediate the in vivo aldosterone and corticosterone responses to 5-bromo-2'-deoxyuridine in rats. 935 56

Senescence is accompanied by a reduced ability to respond to a variety of physical and behavioral stressors. A sizable literature has been devoted to the interplay between hypothalamic-pituitary-adrenocortical axis dysfunction and senescence; yet, the precise interactions remain an enigma. Adrenocorticotropic hormone (ACTH) is secreted in pulsatile bursts generating complex signals in the plasma compartment that must be "read" by adrenocortical cells in order to initiate appropriate secretory responses. We have previously demonstrated subtle differences between young and old rats in the pattern of fluctuations in plasma ACTH concentrations over time, despite no difference in mean levels. The present work addressed the physiological significance of these differences in the plasma ACTH signal by analyzing the corresponding plasma corticosterone concentration time series and the relationship between these two hormones over time. Time series of integrated 10-min ACTH and corticosterone concentrations were collected over 4 h at the time of diurnal activation and analyzed in the time and frequency domains. The time of onset of the diurnal surge occurred 20 min later in old rats, and the ratio of corticosterone to ACTH was less at the time of onset and peak of the diurnal surge. Corticosterone levels were lower in old rats and mean ACTH and corticosterone levels were correlated in young but not old rats, as were maximum levels of the two hormones. Cross-correlation of ACTH and corticosterone time series and comparison of spectra were consistent with smoother fluctuations in plasma corticosterone in old animals with less variability at time scales less than 55 min. We conclude that age may be associated with a delay in diurnal activation of the HPA axis, a loss of sensitivity of adrenal corticosterone secretion to plasma ACTH levels, and a relative loss of high frequency variability in the corticosterone signal, as seen in many physiological systems with age.
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PMID:Coincident plasma ACTH and corticosterone time series: comparisons between young and old rats. 943 15

The acute effects of thyroid hormones on glucocorticoid secretion were studied. Venous blood samples were collected from male rats after they received intravenous 3,5,3'-triiodothyronine (T3) or thyroxine (T4). Zona fasciculata-reticularis (ZFR) cells were treated with adrenocorticotropic hormone (ACTH), T3, T4, ACTH plus T3, or ACTH plus T4 at 37 degrees C for 2 h. Corticosterone concentrations in plasma and cell media, and also adenosine 3',5'-cyclic monophosphate (cAMP) production in ZFR cells in the presence of 3-isobutyl-1-methylxanthine, were determined. The effects of thyroid hormones on the activities of steroidogenic enzymes of ZFR cells were measured by the amounts of intermediate steroidal products separated by thin-layer chromatography. Administration of T3 and T4 suppressed the basal and the ACTH-stimulated levels of plasma corticosterone. In ZFR cells, both thyroid hormones inhibited ACTH-stimulated corticosterone secretion, but the basal corticosterone was inhibited only with T3 > 10(-10) M or T4 > 10(-8) M. Likewise, T3 or T4 at 10(-7) M inhibited the basal- and ACTH-stimulated levels of intracellular cAMP. Physiological doses of T3 and T4 decreased the activities of 3 beta-hydroxysteroid dehydrogenase, 21-hydroxylase, and 11 beta-hydroxylase. These results suggest that thyroid hormones counteract ACTH in adrenal steroidogenesis through their inhibition of cAMP production in ZFR cells.
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PMID:Acute effects of thyroid hormones on the production of adrenal cAMP and corticosterone in male rats. 948 53


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