UNIPROT:P01189 - FACTA Search

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Query: UNIPROT:P01189 (beta-endorphin)
21,003 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The study was aimed at characterizing the changes in hypothalamic-pituitary-adrenal (HPA) axis function during aging in monkey models (Papio hamadryas and Macaca mulatta). It has been established by specific radioimmunoassay and enzyme immunoassay that basal plasma levels of adrenal androgenes (dehydroepiandrosterone-DHEA, dehydroepiandrosterone sulfate-DHEAS) and the early precursors of steroid hormones (pregnenolone and 17-hydroxypregnenolone) progressively decrease with age in baboons and macaques, while cortisol and 11-desoxycortisol concentrations do not change. The old female rhesus monkeys exhibited a higher cortisol and corticosterone response, but a lower DHEAS response to corticotropin-releasing hormone (CRH) administration then the young monkeys. The aged rhesus monkeys also exhibited a decrease of the adrenal cortex resiliency, that was manifested in the deceleration of the decrease of cortisol concentrations after the peak values had been reached in response to ACTH 1-39 administration. At the same time the ACTH 1-24 depot test revealed no age-related changes in the maximum capacity of monkey adrenals to synthesize and secrete cortisol. The aged monkeys also developed less sensitivity of the HPA axis to dexametasone suppression test. The age-related hormonal changes may play an important role in the age-related involutive processes and in the disorders of the adaptive ability of old organisms.
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PMID:Effects of aging on hypothalamic-pituitary-adrenal system function in non-human primates. 1204 68

Adaptation to stressful stimuli, maintenance of homeostasis, and ultimately, survival require bidirectional feedback communication among components of the stress response and immune and endocrine systems. Substantial progress has been made in delineating molecular, cellular, and systemic physiologic mechanisms underlying this communication, particularly mechanisms that target the immune system. For example, our understanding of the immunomodulatory activities of numerous neuroendocrine mediators, such as cortisol, estrogen, testosterone, DHEA, catecholamines, corticotropin-releasing hormone, and adenosine, has advanced substantially. Substantial progress has also been made in defining how abnormalities involving these factors may contribute to the initiation, progression, and severity of autoimmune rheumatic diseases, particularly rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). For RA, the available data support the view that inflammatory and immune system inhibitory mechanisms, involving the hypothalamic-pituitary-adrenal (HPA) axis and sympathetic nervous system are deficient. Age, gender, and reproductive status acting, in part, through gonadal hormonal effects on disease susceptibility genes also appear likely to modulate the inhibitory stress response systems and immune function. Animal model data also have provided direct evidence that many autoimmune disease regulatory genes are gender influenced. For SLE, a growing body of recent data indicates that estrogens and androgens exert contrasting effects on B-lymphocytes (i.e., estrogens enhance and testosterone suppresses autoantibody production). These observations provide potential new insights into SLE pathogenesis and gender differences in prevalence. Continued investigation will refine our understanding of these observations and will uncover even more extensive interactions of the nervous, immune, and endocrine systems. Moreover, it is highly likely that improved understanding of these interactions will translate into improved therapy for the rheumatic diseases.
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PMID:Neuroimmunoendocrinology of the rheumatic diseases: past, present, and future. 1211 54

Steroid synthesis inhibitors are commonly used in the treatment of patients with Cushing's disease, but may also improve psychopathology in hypercortisolemic depressed patients. Since glucocorticoids exert a negative feedback at pituitary and supra-pituitary levels, the inhibition of steroid synthesis may lead to increased expression of corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP). We studied the effect of treatment with 800 mg ketoconazole (3 weeks) upon the concentrations of basal plasma cortisol in the evening, corticosteroid-binding globulin (CBG), dehydroepiandrosterone-sulfate (DHEA-S), and ACTH as well as the concentrations of cortisol, CRH, and AVP in cerebrospinal fluid (CSF) at 8.30 h in 10 healthy, male volunteers. While we found cortisol plasma concentrations to be unchanged, we noted a significant increase in ACTH (post: 45.1+/-43.5; pre: 14.2+/-5.2 pmol/l; F(1,8)=9.78, p<0.02) and CBG concentrations (post: 38.8+/-4.3; pre: 31.9+/-4.2 microg/l), but DHEA-S plasma concentrations declined (post: 1.75+/-1.83; pre: 2.75+/-2.80 mg/l; F(1,8)=7.9, p<0.03). CRH concentrations in CSF were unchanged after treatment (post: 62.5+/-15.9; pre: 63.7+/-13.9 pg/ml), while there was a trend for AVP concentrations to rise during treatment (post: 2.52+/-1.18; pre: 1.92+/-0.96 pg/ml; paired t=-1.9, p<0.1). Cortisol CSF concentrations declined in the elderly (pre: 52.5+/-23.2; post: 26.7+/-4.6 nmol/l), but not in the young subgroup (pre: 15.6+/-11.3; post: 27.7+/-9.4 nmol/l). We thus conclude that the treatment of healthy controls with steroid-synthesis inhibitors does not lead to a major increase in CRH secretion.
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PMID:Steroid synthesis inhibition with ketoconazole and its effect upon the regulation of the hypothalamus-pituitary-adrenal system in healthy humans. 1258 91

It is widely accepted that the classical dose of 250.0 microg ACTH (1-24) (tetracosactin) is clearly supra-maximal while 1.0 and 0.03 microg have been shown as the maximal and the lowest stimulatory ACTH doses for cortisol (F) secretion in normal young subjects. Testing with low ACTH dose would better evaluate adrenal sensitivity to corticotropin. The aims of the present study were: a) to clarify the adrenal sensitivity to ACTH in patients with different duration of corticotroph insufficiency by testing with low and very low tetracosactin doses; and b) to evaluate diagnostic implication regarding the ability of ACTH tests to distinguish patients with corticotroph insufficiency from normal subjects. In 24 hypopituitaric patients (HYPOPIT, 15 male and 9 female, age 22-50 yr, BMI: 22-26 kg/m2) with corticotrophin deficiency we studied the F, DHEA and aldosterone (A) responses to challenges with low ACTH doses (0.06 or 0.5 microg iv at 0 min) followed by 250 microg iv (at +60 min). The results in HYPOPIT were compared with those recorded in 12 normal controls (NS, 6 male and 6 female, age 22-34 yr, BMI: 20-25 kg/m2). Basal F and DHEA levels in HYPOPIT were lower than in NS, while A levels were similar in both groups. The F responses to ACTH in HYPOPIT were dose-independent and markedly lower (p < 0.0001) than in NS. After the 0.06 and 0.5 microg ACTH dose, 16% of HYPOPIT patients showed AF peak within the range of normal response. No HYPOPIT showed AF peak within the normal range after 250 microg ACTH. The DHEA responses to ACTH in HYPOPIT were dose-independent and markedly lower than in NS (p < 0.0001). Overlap between individual DHEA responses in HYPOPIT and NS was present after 0.06 microg and 0.5 microg but not after 250 microg tetracosactin. The A responses in HYPOPIT were dose-dependent and overlapped with those in NS. The adrenal responses to ACTH in HYPOPIT were not associated with the duration of the disease. In conclusion, the present study shows that the mean F and DHEA but not the A responses to ACTH (1-24) are markedly impaired in hypopituitaric patients with corticotroph insufficiency independently of the duration of the disease. The impaired F and DHEA response to ACTH is also independent of the dose, suggesting the existence of relatively enhanced sensitivity of the fasciculata and reticularis adrenal zone to ACTH but meantime remarkable impairment of the adrenal function due to corticotrophin deficiency. In the present study, testing with submaximal ACTH doses did not distinguish patients with secondary adrenal insufficiency from normal subjects.
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PMID:Hypopituitaric patients with corticotropin insufficiency show marked impairment of the cortisol response to ACTH (1-24) independently of the duration of the disease. 1260 26

Dehydroepiandrosterone (DHEA) and its sulfated ester (DHEA-S) are corticotropin-dependent adrenal androgen precursors that are uniformly low in treated patients with corticotropin deficiency. There are no data investigating the diagnostic value of DHEA-S measurements in the prospective assessment of adrenal function. This study examined serum DHEA-S levels as possible markers for hypothalamic- pituitary-adrenal (HPA) function in patients with large pituitary adenomas. Patients were characterized to have normal HPA (n = 47) or abnormal HPA (ABN-HPA, n = 35) function based on their respective responses to insulin-induced hypoglycemia. Patients also underwent low-dose Cortrosyn (1 micro g, LDC) and standard-dose Cortrosyn stimulation testing. All patients with ABN-HPA had very low age- and gender-matched serum DHEA-S levels. When the normal response to LDC was set at a cortisol level of at least 18.1 micro g/dl, 10 of 31 patients with ABN-HPA exhibited normal responses. Receiver operating characteristic curves for baseline DHEA-S and for maximal cortisol responses to LDC had areas of 0.984 (confidence interval, 0.962-1.000) and 0.893 (confidence interval, 0.817-0.969), respectively. LDC- or SDC-stimulated serum cortisol levels have significant limitations in defining HPA function. A normal age- and gender-specific serum DHEA-S level makes the diagnosis of corticotropin deficiency extremely unlikely. However, when serum DHEA-S levels are low, further testing is necessary to define HPA function.
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PMID:The value of dehydroepiandrosterone sulfate measurements in the assessment of adrenal function. 1460 64

The central nervous system (CNS) is one of the main target tissues for sex steroid hormones, which act both through genomic mechanisms, modulating synthesis, release, and metabolism of many neuropeptides and neurotransmitters, and through nongenomic mechanisms, influencing electrical excitability, synaptic function, and morphological features. The identification of the brain as a de novo source of neurosteroids modulating cerebral function, suggests that the modifications in mood and cognitive performances occurring in postmenopausal women could also be related to a modification in the levels of neurosteroids, particularly allopregnanolone and DHEA, GABA-A agonist, and antagonist, respectively. The selective estrogen receptor modulators (SERMs) are compounds that activate the estrogen receptors with different estrogenic and antiestrogenic tissue-specific effects. In addition to the effects of the classic steroid hormones on the CNS, the study of selective estrogen receptor modulators impact on the neuroendocrine system has recently provided encouraging results, indicating that raloxifene analog LY 117018 and the new generation SERM EM-652 have an estrogen-like action on beta-endorphin and on allopregnanolone in ovariectomized rats, while they exert an anti-estrogenic effect in fertile rats and in ovariectomized rats treated with estrogens. In addition, raloxifene administration in postmenopausal women plays an estrogen-like effect on circulating beta-EP and allopregnanolone levels, and it restores the response of beta-EP and allopregnanolone to neuroendocrine tests. In conclusion, the positive effects of HRT on mood and cognition in postmenopausal women occur via the modulation of neuroendocrine pathways and probably also of neurosteroidogenesis. The effects of raloxifene on mood and cognition encourage the efforts in the research of an ideal estrogen replacement therapy, showing all the positive effects of estrogens and fewer side effects.
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PMID:CNS: sex steroids and SERMs. 1464 45

Hyperactivity of hypothalamus-pituitary-adrenal (HPA) axis in anorexia nervosa (AN) has been demonstrated and is likely to reflect a central nervous system (CNS)-mediated effect of starvation. Alterations in the adrenal response to ACTH in AN have also been reported by some authors. In order to define the adrenal sensitivity to ACTH in this condition, we studied cortisol (F), aldosterone (A) and DHEA responses to the sequential administration of low and supramaximal ACTH 1-24 doses (0.06 microg/m2 ACTH 1-24 iv at 0 min and 250 microg ACTH 1-24 iv at +60 min, respectively) in 10 young women with AN [ANW, age 21.2 +/- 0.9 yr, body mass index (BMI) 15.7 +/- 0.6 kg/m2]. The results in this group were compared with those recorded in 10 healthy normal women (HW, 23.4 +/- 1.1 yr, 21.9 +/- 0.9 kg/m2). In ANW urinary F levels were similar to those in HW. Basal serum F, A and DHEA levels in ANW were not significantly different from those in HW. In HW the lowest ACTH dose induced a significant (p<0.05) increase of F, A and DHEA. The maximal ACTH dose induced F, A and DHEA increases greater (p<0.05) than those induced by the lowest ACTH dose. In ANW both ACTH doses induced significant (p<0.05) F and DHEA increases which were not significantly different from those in HW, though a trend toward a lower cortisol response after ACTH 0.06 microg/m2 in ANW was present. Like in HW, in ANW the maximal ACTH dose induced F and DHEA increases greater (p<0.01) than those induced by the lowest dose. Unlike HW, in ANW A levels did not increase after the lowest ACTH dose while they increased after the maximal one overlapping the response in HW. In conclusion, the cortisol and DHEA responses to a very low and a supra-maximal ACTH dose in patients with AN were similar to those in healthy subjects, indicating that the sensitivity to ACTH of the fasciculata and reticularis adrenal zones is preserved in this condition. On the other hand, a reduced sensitivity to ACTH of the glomerularis adrenal zone in patients with AN is suggested by the lack of aldosterone response to the lowest corticotropin dose.
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PMID:The adrenal sensitivity to ACTH stimulation is preserved in anorexia nervosa. 1527 75

Dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS) are the principal C19 steroids produced by the human adrenals. Their plasma levels decline to less than 20% of their maximal value during aging. Because these steroids appear to play a role in the maintenance of immunity, musculoskeletal integrity, and cardiovascular health, age-associated declines in adrenal androgen production may contribute to decreased immune function, osteoporosis, and atherosclerosis. Production of DHEA and DHEAS has been localized to the zona reticularis (ZR) of the adrenal cortex and can be modulated by intra-adrenal or extra-adrenal modulators. Extra-adrenal modulators include corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), insulin, and transforming growth factor beta (TGF-beta). Intra-adrenal regulators include enzymes and proteins involved in the steroidogenic pathway, specifically 17,20 lyase activity and DHEA sulfotransferase (DST). The natural histories of the emergence of adrenal androgen production and the ontogeny of the ZR appear to correlate closely. In addition, aging results in a decline in adrenal androgen production, and our data suggest a parallel diminution in the area represented by the ZR. This decline in the ZR may result from apoptosis, cellular and humoral immunity, or a reduction in the replicative capacity of the cells of the ZR.
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PMID:Adrenal androgens and aging. 1563 95

Dehydroepiandrosterone (DHEA) and its sulfate (DHEAS) are the main adrenal androgens (AAs) produced in humans. Production of these steroids, like that of cortisol, is under the control of hypothalamic corticotropin-releasing hormone (CRH) and pituitary ACTH. Other factors, however, appear to be involved in AA secretion because there are many instances in which their circulating levels do not change in parallel to those of cortisol. Apart from physiological alterations associated with fetal adrenal regression, adrenarche and aging, the main instances of divergence in AA production compared with those of corticosteroids occur when immune function is activated or is aberrant. Relative reductions in DHEA and DHEAS have been noted in subjects with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), human immunodeficiency virus (HIV) and autoimmune deficiency syndrome (AIDS), sepsis, and trauma. In some instances, differences in the AA responses have been linked to a clinical course. The mechanisms for impairments in AA production in the absence of suppressed corticoid secretion are unclear but may involve circulating cytokines or locally released mediators from immune system cells in the adrenal gland. There also is evidence that DHEA and DHEAS play a role in immune competence, displaying biological effects opposite to those of corticosteroids.
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PMID:Adrenal androgens and the immune system. 1563 95

Dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS) age-related withdrawal is very likely to be involved in the aging process and the onset of age-related diseases, giving rise to the question of whether preventing or compensating the decline of these steroids may have endocrine and clinical benefits. The aim of the present trial was to evaluate the endocrine, neuroendocrine and clinical consequences of a long-term (1 year), low-dose (25 mg/day) replacement therapy in a group of aging men who presented the clinical characteristics of partial androgen deficiency (PADAM). Circulating DHEA, DHEAS, androstenedione, total testosterone and free testosterone, dihydrotestosterone (DHT), progesterone, 17-hydroxyprogesterone, allopregnanolone, estrone, estradiol, sex hormone binding globulin (SHBG), cortisol, follicle stimulating hormone (FSH), luteinizing hormone (LH), growth hormone (GH) and insulin-like growth factor 1 (IGF-1) levels were evaluated monthly to assess the endocrine effects of the therapy, while beta-endorphin values were used as a marker of the neuroendocrine effects. A Kupperman questionnaire was performed to evaluate the subjective symptoms before and after treatment. The results showed a great modification of the endocrine profile; with the exception of cortisol levels, which remained unchanged, DHEA, DHEAS, androstenedione, total and free testosterone, DHT, progesterone, 17-hydroxyprogesterone, estrone, estradiol, GH, IGF-1 and beta-endorphin levels increased significantly with respect to baseline values, while FSH, LH and SHBG levels showed a significant decrease. The Kupperman score indicated a progressive improvement in mood, fatigue and joint pain. In conclusion, the present study demonstrates that 25 mg/day of DHEA is able to cause significant changes in the hormonal profile and clinical symptoms and can counteract the age-related decline of endocrine and neuroendocrine functions. Restoring DHEA levels to young adult values seems to benefit the age-related decline in physiological functions but, however promising, placebo-controlled trials are required to confirm these preliminary results.
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PMID:Long-term low-dose dehydroepiandrosterone replacement therapy in aging males with partial androgen deficiency. 1567 38

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