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)

Hypersecretion of corticotropin-releasing hormone (CRH) and resulting hypercortisolism have been implicated in the pathogenesis of major depression. To test this CRH hypersecretion hypothesis, cerebrospinal fluid (CSF) was continuously withdrawn from 11:00 AM to 5:00 PM via an indwelling subarachnoid catheter (placed at 8:00 AM), and immunoreactive CRH concentrations were determined at 10-min intervals in 10 depressed patients, the majority of whom exhibited at least one "atypical" symptom, and in 15 normal volunteers. CSF CRH was low, plasma adrenocorticotropin (ACTH) tended to be low, and plasma cortisol was normal in the depressed patients. Also, tobacco smokers had lower CSF CRH than nonsmokers. CRH increased acutely in response to lumbar puncture, had a brief half-life, showed rapid variability in concentration over time, and displayed a diurnal concentration rhythm that was preserved in fasting individuals and in most depressed patients. CSF CRH did not correlate with plasma ACTH or cortisol; this and its rapidly fluctuating levels suggest a primarily extrahypothalamic origin of lumbar CSF CRH.
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PMID:Low cerebrospinal fluid corticotropin-releasing hormone concentrations in eucortisolemic depression. 923 8

The hypothalamic-pituitary-adrenal (HPA) axis and the female reproductive system are intertwined and exhibit a complex relationship. Thus, the HPA axis exerts profound, mostly inhibitory effects, on the reproductive axis, with corticotropin-releasing hormone (CRH) and CRH-induced propiomelanocortin peptides inhibiting hypothalamic GnRH secretion, and with glucocorticoids inhibiting pituitary LH and ovarian estrogen and progesterone secretion and rendering estrogen-target tissues, such as the endometrium, resistant to the gonadal steroid. These effects of the HPA axis are responsible for the "hypothalamic" amenorrhea of stress, depression and eating disorders, and the hypogonadism of Cushing's syndrome. Conversely, estrogen directly stimulates the CRH gene, which may explain the slight hypercortisolism of females and the preponderance of depressive, anxiety, and eating disorders, as well as Cushing's disease in women. Interestingly, several components of the HPA axis and their receptors are present in reproductive tissues, as autocoid regulators of their various functions. These include ovarian and endometrial CRH, which may participate in the inflammatory processes of the ovary, that is, ovulation and luteolysis, and of the endometrium, that is, implantation and menstruation. Finally, the hypercortisolism of the latter half of pregnancy can be explained by high levels of placenta CRH in plasma. This hypercortisolism causes a transient adrenal suppression in the postpartum period, which may explain the postpartum blues/depression and autoimmune phenomena of this period.
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PMID:The hypothalamic-pituitary-adrenal axis and the female reproductive system. 923 54

A 17-year-old female with a large mass in the left thorax presenting with ectopic Cushing's syndrome is described. Biochemical evaluation revealed a corticotropin(ACTH)-dependent hypercortisol state. Surgical resection of the tumour resulted in clinical remission and correction of hypercortisolism and normal plasma ACTH levels. The histology was that of an atypical carcinoid. Bronchial carcinoid tumour is an extremely uncommon but well recognised cause of ectopic Cushing's syndrome. These patients may pose diagnostic dilemma in distinguishing form those with Cushing's disease because of the similarity in the clinical, biochemical and radiologic findings.
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PMID:Ectopic Cushing's syndrome in a young female with atypical [corrected] bronchial carcinoid tumour. 926 52

Pituitary function was assessed before and after transsphenoidal hypophysectomy in 39 dogs with pituitary-dependent hyperadrenocorticism (PDH). Anterior pituitary function was investigated using combined administration of four hypophysiotropic releasing hormones (corticotropin-releasing hormone (CRH), GHRH, GnRH, and TRH) with measurements of ACTH, cortisol, GH, LH, prolactin (PRL), and TSH Pars intermedia function was assessed by measurements of basal plasma alpha-MSH concentrations and adrenocortical function by baseline urinary corticoid/creatinine ratios. At eight weeks after hypophysectomy basal plasma ACTH, cortisol, GH, LH, PRL, and TSH concentrations were significantly lower than before surgery. In seven dogs with elevated alpha-MSH concentrations, the values returned to the normal level after surgery. In the combined anterior pituitary function test there were no plasma GH, LH, PRL, and TSH responses to stimulation, whereas plasma ACTH and cortisol responses were small but significant. Remission of hyperadrenocorticism was obtained in 35 dogs and recurrences occurred in 3 of these within 16 months postoperatively. At 8 weeks after hypophysectomy, these 3 dogs were not discernible, with respect to residual pituitary and adrenocortical function, from the 32 dogs with persisting remission. Urinary corticoid/creatinine ratios in the latter group of dogs did not increase during 22 months after hypophysectomy. In contrast to the presurgical findings, at 8 weeks after hypophysectomy there were significant positive correlations between baseline urinary corticoid/creatinine ratios and basal levels and responses for ACTH, indicating return to normal function of the pituitary-adrenocortical axis. It is concluded that among the adenohypophyseal cells present in the sella turcica after hypophysectomy, the corticotropes have a distinct behavior. Much more so than the other cell types, the unaffected corticotropes tend to remain functional, or a repressed reserve fraction of corticotropes may become functional. This may be due to the removal of the hypothalamic influence of a postulated corticotropin-release inhibiting factor or a diminished inhibitory influence of a postulated paracrine factor. The corticotropes may maintain normocorticism, but may also lead to mild recurrence after relatively long periods of remission.
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PMID:Residual pituitary function after transsphenoidal hypophysectomy in dogs with pituitary-dependent hyperadrenocorticism. 948 98

The rapid cosyntropin stimulation test offers a simple means for detecting adrenal insufficiency. In contrast, assessment of suspected hypercortisolism (Cushing's syndrome) is difficult because cortisol levels fluctuate with intermittent release of corticotropin from the pituitary or from tumors. Also, a number of medications affect cortisol levels, leading to false-positive or false-negative results. The classic low-dose followed by high-dose dexamethasone test is cumbersome, and other, simpler studies, such as the overnight high-dose dexamethasone suppression test, may prove more practical and cost-effective. With both high and low levels of adrenal glucocorticoids, awareness and early recognition of the symptoms are important. An endocrinologist should be consulted when the overnight dexamethasone suppression test or the 24-hour urine cortisol collection is abnormal or if clinical suspicion is high despite normal results on screening tests.
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PMID:Assessment of adrenal glucocorticoid function. Which tests are appropriate for screening? 967 62

Chronic food restriction (FR) of rats and mice results in moderate hyperadrenocorticism, which may play a role in activating cellular mechanisms that retard aging. Previously, we reported that the FR-induced hyperadrenocorticism is not due to an activated hypothalamo-pituitary unit. Therefore, we investigated in a series of experiments whether adrenal responsiveness to adrenocorticotropic hormone (ACTH), in vitro and in vivo, is enhanced by FR. Three mo-old male Fischer 344 rats were either given free access to food (AL rats) or restricted to 60% of food consumed by AL rats (FR rats) from 6 wk of age. They were killed by decapitation in the morning (AM) and afternoon (PM) when endogenously circulating corticosterone levels are at their nadir and peak, respectively. In vitro, adrenal glands from FR rats (1.5 mo FR) produced more corticosterone per mg at all doses of ACTH than those from AL rats in both the AM and PM (diet main effect, P < 0.001). FR (1.5 to 2.5 mo) also enhanced adrenal responsiveness to physiologic (diet main effect, P < 0.05) and superphysiologic (diet main effect, P < 0.001) levels of ACTH administered in vivo to dexamethasone-treated rats. ACTH-receptor (ACTH-R) mRNA, normalized to adrenal mass or to total RNA, was not influenced by FR (1.5 mo). However, adrenal ACTH-R mRNA, as well as adrenal mass, per unit body weight was greater in FR than in AL rats (diet main effect, P < 0.001). These results indicate that enhanced adrenocortical responsiveness to ACTH plays a major role in the hyperadrenocortical state of chronically FR rats.
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PMID:Adrenocortical responsiveness to adrenocorticotropic hormone is enhanced in chronically food-restricted rats. 973 99

In the rat, high-dose corticosterone (Cort) administration, the hypercortisolism of starvation, and adrenalectomy are all associated with decreased food intake and weight loss. We report here a study of the effects of high-dose Cort administration, starvation, and adrenalectomy on two peripheral hormones known to influence food intake and energy use, insulin and leptin. We also studied the impact of these interventions on the levels of type 2 corticotropin-releasing hormone receptor (CRHR-2) mRNA in the hypothalamic paraventricular nucleus (PVN) and ventromedial hypothalamus (VMH). The VMH is classically referred to as the satiety center because electrical stimulation of the VMH leads to inhibition of food intake, whereas CRHR-2 are thought to transduce the profound anorexogenic effects of CRH or its related peptide urocortin. Starvation and adrenalectomy each lowered plasma insulin and leptin levels and were associated with decrements in CRHR-2 mRNA levels in the VMH. Cort administration increased plasma leptin levels profoundly, as well as plasma insulin levels and the levels of VMH CRHR-2 mRNA. Under all experimental conditions, a positive correlation was seen between plasma leptin levels and VMH CRHR-2 mRNA. These data suggest that decreased food intake and weight loss after high-dose Cort administration at least partially depend on the profound impact of Cort on plasma leptin secretion in the rat; they suggest, moreover, an additional mechanism for the satiety-inducing effects of leptin, namely increasing CRHR-2 in the VMH. The concordance of a fall in plasma insulin and leptin levels with the fall in VMH CRHR-2 mRNA levels further supports the idea that compensatory responses during starvation and adrenalectomy include not only the disinhibiting effects of reduced insulin and leptin levels on appetite through already-described mechanisms but also via an effect of leptin on VMH CRHR-2. Neither Cort administration, starvation, nor adrenalectomy influenced the levels of CRHR-2 mRNA in the PVN, suggesting that these receptors are differentially regulated in different hypothalamic regions.
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PMID:Altered expression of type 2 CRH receptor mRNA in the VMH by glucocorticoids and starvation. 975 44

Corticotropin (ACTH) pharmacokinetics was assessed in 10 normal dogs receiving exogenous ACTH (0.5 U/kg, i.v.). A two-compartment open model was most appropriate for description of exogenous ACTH pharmacokinetics. The apparent distribution and elimination rate constants (alpha and beta) were 7.4 +/- 2.7 x 10(-2) min(-1) and 5.5 +/- 3.8 x 10(-3) min(-1), respectively. Area under the concentration-time curve (AUC) was 2.91 +/- 0.78 x 10(4) pg x min/mL, mean residence time (MRT) was 45.0 +/- 12.2 min, the distribution half-life (t1/2alpha) was 9.4 min (harmonic mean), and the elimination half-life (t1/2beta) was 128 min (harmonic mean). The total body clearance of ACTH (ClB) was 1.83 +/- 0.46 x 10(4) mL x min/kg and volume of distribution (Vd(area)) was 30 +/- 15 L/kg. Corticotropin pharmacokinetics was also assessed in 12 client owned dogs, six dogs with non adrenal illness (NAI) and six dogs with hyperadrenocorticism (HAC), receiving exogenous ACTH (0.5 U/kg, i.v.). For these patients, data was best fitted to a one-compartment open model. In dogs with NAI, the AUC was 6.23 +/- 0.62 x 10(5) pg x min/mL, MRT was 38.7 +/- 12 min, the apparent elimination rate constant (k(el)) was 0.26 +/- 0.0017 min(-1) elimination half-life was 26.7 min, ClB was 0.84 +/- 0.1 x 10(4) mL/min/kg, and Vd(area) was 31.9 +/- 5.7 L/kg. In dogs with HAC, AUC was 4.74 +/- 0.23 x 10(5) pg x min/mL, MRT was 20.4 min, k(el) was 0.034 +/- 0.009 min(-1), half-life was 20.4 min, CIB was 1.06 +/- 6.0 x 10(4) mL/min/kg and Vd(area) was 29.7 +/- 6.7 L/kg. Dogs with pituitary-dependent hyperadrenocorticism showed more rapid elimination and clearance of exogenous corticotropin than dogs with NAI.
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PMID:Pharmacokinetics of exogenous corticotropin in normal dogs, hospitalized dogs with non adrenal illness and adrenopathic dogs. 981 37

Leptin, the protein product of the obese (ob) gene, has been suggested to play a role in the regulation of food intake. As depressive episodes are frequently characterized by loss of appetite, reduced food intake and weight loss, altered leptin secretion might also be expected in patients with depression. Therefore, we examined nocturnal (10.00 p.m. to 7.00 a.m.) secretion of leptin, cortisol, ACTH and growth hormone (GH) in a group of 15 patients with depression and age- and sex-matched controls (age range 23-71 years). In addition, the effects of pulsatile administration of growth hormone-releasing hormone (GHRH), thought to be an endogenous antagonist of corticotropin-releasing hormone (CRH), which in turn is believed to play a critical role for the pathophysiology of depression, on nocturnal hormone secretion were assessed. Patients with depression showed a trend towards elevated nocturnal cortisol secretion (F = 3.8, p < 0.05). Nocturnal serum leptin was significantly higher in patients, despite a reported weight loss (F = 8, p < 0.05), but showed the same sexual dimorphism as in controls (F = 20.9, p < 0.01). No significant differences were seen between patients and controls with regard to plasma GH and ACTH. GHRH treatment increased GH secretion in both patients and controls, while the other hormones were not affected. Furthermore, serum leptin was correlated with body mass index (BMI) in controls, but not in patients with depression, supporting an altered regulation of leptin secretion in depressive illness. Finally, we provide some evidence that in young female patients the normal nocturnal leptin surge is blunted. As glucocorticoids can prevent the fasting-induced decline in serum leptin, we propose that hypercortisolism in depression might counteract the reduction in leptin secretion caused by decreased food intake and weight loss. Elevated serum leptin in depression might in turn further promote CRH release, as shown in animals and, hence, contribute to HPA system hyperactivity seen in depression.
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PMID:Elevated nocturnal profiles of serum leptin in patients with depression. 984 57

The cardinal clinical manifestations of major depression with melancholic features include sustained anxiety and dread for the future as well as evidence of physiological hyperarousal (e.g., sustained hyperactivity of the two principal effectors of the stress response, the corticotropin-releasing-hormone, or CRH, system, and the locus ceruleus-norepinephrine, or LC-NE, system). Sustained stress system activation in melancholic depression is thought to confer both behavioral arousal as well as the hypercortisolism, sympathetic nervous system activation, and inhibition of programs for growth and reproduction that consistently occur in this disorder. Data also suggest that activation of the CRH and LC systems in melancholia are involved in the long-term medical consequences of depression such as premature coronary artery disease and osteoporosis, the two-three-fold preponderance of females in the incidence of major depression, and the mechanism of action of antidepressant drugs. In addition, recent data reveal important bidirectional interactions between stress-system hormonal factors in depression and neural substrates implicated in many discrete behavioral alterations in depression (e.g., the medial prefrontal cortex, important in shifting affect based on internal and external cues, the mesolimbic dopaminergic reward system, and the amygdala fear system). We have also advanced data indicating that the hypersomnia, hyperphagia, lethargy, fatigue, and relative apathy of the syndrome of atypical depression are associated with concomitant hypofunctioning of the CRH and LC-NE systems. These data indicate the need for an entirely different therapeutic strategy than that used in melancholia for the treatment of atypical depression, and they suggest that this subtype of major depression will be associated with its own unique repertoire of long-term medical consequences.
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PMID:The endocrinology of melancholic and atypical depression: relation to neurocircuitry and somatic consequences. 989 54


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