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

As is obvious from the previous discussions, obesity is associated with a wide variety of changes in endocrine parameters (Table 1). Some of these changes, such as the reduction in SHBG without change in serum free testosterone levels, reflect merely laboratory abnormalities that may influence interpretation of diagnostic tests but have no important physiologic relevance. Other abnormalities have major clinical impact, such as hyperestrogenemia-endometrial carcinoma and hyperlipidemia-coronary artery disease. In some cases, endocrine changes in obesity are beneficial--that is, hyperestrogenemia leading to lower incidence of osteoporosis. In other cases, such as the profound suppression of growth hormone output in obesity, the physiologic relevance is unknown. Several endocrine changes in obesity, such as the impaired response of many hormones (growth hormone, prolactin, vasopressin, corticotropin) to insulin-induced hypoglycemia and elevated endorphin levels, suggest hypothalamic dysfunction. Furthermore, the failure of all of these abnormalities to be normalized after weight reduction raises the possibility of an underlying disorder leading to both endocrine dysfunction and obesity, rather than the endocrine dysfunction being simply a consequence of the obesity. Successful elucidation of the pathogenesis of obesity, which might then lead to much needed specific treatment modalities, may be advanced if we can solve some of these puzzles.
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PMID:Endocrine aspects of obesity. 264 1

Weanling, male and female, stroke-prone, spontaneously hypertensive rats (SP/SHR) were fed either a regular diet, a low protein diet derived from fish tissue + 1% saline drinking water, or the fish diet + 1% saline + daily injections of 0.1 mg Enovid/100 g bw/sc. After 48 days, the Enovid-treated animals developed acute and lethal strokes characterized by massive thrombonecrogenic lesions of the parietal lobe. The blood pressure of the Enovid-treated SP/SHR rose most acutely. The low protein fish diet was markedly catabolic and caused hyperlipidemia, hyperglycemia, elevated ACTH and beta-endorphin levels concomitant with reduced gonadotrophic function. Treatment with Enovid caused severe exacerbation of all of the foregoing changes. It is proposed that a low protein fish diet + 1% saline will accelerate the appearance of strokes in SP/SHR and that Enovid will enhance this effect through its anti-gonadotrophic activity and ability to stimulate increased pituitary-adrenal secretion.
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PMID:Enovid-induced exacerbation of the propensity for stroke in low protein fish diet-fed stroke-prone/SHR. 631 4

We report a young female case of alcoholic liver injury accompanied with various metabolic and endocrinological disorders. A 29 year-old woman was admitted because of general fatigue and hyperlipidemia. She was a heavy drinker. Laboratory data on admission revealed liver dysfunction and hyperlipidemia (type II b) with a quite high serum gamma-glutamyltranspeptidase (gamma GTP) level. The microscopic finding of the liver biopsy specimen showed fatty metamorphosis and ballooning of hepatocytes, and she was diagnosed as heavy alcoholic liver injury. The endocrinological examination revealed the elevated plasma cortisol level, though the urinary 17-hydroxycorticoids (17-OHCS) and 17-ketosteroids (17-KS) excretion and the plasma adrenocorticotropic hormone (ACTH) level were reduced. Cortisol secretion showed the normal circadian rhythm and the normal response to ACTH provocation. The levels of plasma triiodothyronine (T3), thyroxine (T4), and thyroid stimulating hormone (TSH) were also reduced. These endocrinological and metabolic disorders were normalized in company with recovery of the liver function by temperance, diet therapy and nutritional education. Thus, these abnormalities were considered to be resulted from the alcoholic liver injury and the effect of the ethanol to the hypothalamic-pituitary system.
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PMID:[Alcoholic liver injury accompanied with various metabolic and endocrinological disorders--a case report]. 822 58

There are several hypothalamic theories of aging, none of which has been validated. An approach to validation is to search for consequences of anatomic ablations of hypothalamic regions that are functional hallmarks of aging, or consequences of ablation that postpone the appearance of hallmarks of aging or extend longevity. Ablation of the hypothalamic ventromedial nucleus (VMN) in the weanling rat is associated with subsequent increased body fat, glucose intolerance, hyperlipidemia, and decreased renal function. Each of these consequences is characteristic of aging in humans and in several animal models of aging. Ablation of the hypothalamic dorsomedial nucleus (DMN) in the weanling rat leads to a symmetrically smaller animal with normal glucose and lipid metabolism, decreased body fat for size, and reduced risk of decreased renal function and circulating IGF-I levels. These are findings consistent with calorie restriction models in rodents that significantly extend life span. This review compares outcomes of lesions in the VMN, DMN, and lateral hypothalamic area (LHA) for relevance to aging. To establish a relationship between these anatomic areas of the hypothalamus and aging, it is concluded that the VMN, DMN, and LHA lesions should be examined for impact on longevity and compared with data obtained from simultaneously studied intact ad-lib-fed and 40% calorie-restricted animals. Lesioned animals also should be rigorously studied for neurotransmitters (e.g., neuropeptide Y, beta-endorphin, serotonin, corticotropin-releasing factor, and galanin), and for behavioral changes consistent with aging, for accumulation of specific tissue lipofuscin and amyloid that are associated with normal aging and for other age-dependent findings, such as incidence of tumors and cataract.
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PMID:Aging and the hypothalamus: research perspectives. 870 Sep 56

Hypothalamic neuropeptide Y (NPY) and corticotropin-releasing hormone (CRH) influence feeding and levels of plasma glucose, insulin, free fatty acids, and triglycerides. Treatment of genetically obese, ob/ob mice, with dopamine receptor D(1)/D(2) agonists normalizes hyperphagia, body weight gain, hyperglycemia, and hyperlipidemia. We therefore examined whether levels of NPY and CRH immunoreactivity in discrete hypothalamic nuclei are altered in ob/ob mice, and whether dopaminergic treatment reverses this alteration. Female ob/ob mice were treated daily at 1 h after light onset with the D(1)/D(2) agonists, SKF-38393 (20 mg/kg) and bromocriptine (15 mg/kg), respectively or vehicle for 2 weeks. Such treatment, while normalizing body weight gain and hyperglycemia, also significantly reduced elevated NPY immunoreactivity in the suprachiasmatic (by 39%), intergeniculate (by 43%), paraventricular (PVN; by 31%), and arcuate (by 41%) nuclei in obese mice to levels observed in lean mice. This treatment also caused a 45-50% decline in levels of CRH in the PVN and dorsomedial hypothalamus compared to obese controls to levels observed in lean mice. Taken together, these findings suggest that dopaminergic D(1)/D(2) receptor coactivation may improve hyperphagia, hyperglycemia, and obesity in the ob/ob mouse, in part, by normalizing elevated levels of both NPY and CRH.
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PMID:Dopaminergic agonists normalize elevated hypothalamic neuropeptide Y and corticotropin-releasing hormone, body weight gain, and hyperglycemia in ob/ob mice. 1064 1

The decline of plasma dehydroepiandrosterone (DHEA) and maintenance of glucocorticoid levels with increasing age contribute to excess body fat accumulation, hyperglycaemia, hyperlipidaemia, hyperinsulinaemia and cancer. Although opposing actions of DHEA and corticosterone have been proposed in a rat model, the effects and action mechanisms of DHEA on rat adrenal zona fasciculata-reticularis (ZFR) cells are still unclear. This study addressed the effects of DHEA on corticosterone release, cellular cAMP production, the functions of steroidogenic enzymes and the expression levels of steroidogenic acute regulatory protein (StAR) and cytochrome P450 side-chain cleavage enzyme (P450scc). ZFR cells were incubated with DHEA in the presence or absence of adrenocorticotropin (ACTH), 8-Br-cAMP, forskolin, 25-OH-cholesterol, pregnenolone, progesterone or deoxycorticosterone at 37 degrees C for 30 min, 1 h or 5 h and the concentration of corticosterone or pregnenolone measured subsequently in the media by RIA. The cells were used to measure the content of cAMP by RIA and to extract protein for Western blot or mRNA for RT-PCR analysis. The data demonstrated that (1) DHEA inhibited ACTH-, 8-Br-cAMP-, 25-OH-cholesterol-, pregnenolone-, progesterone- or deoxycorticosterone-stimulated corticosterone release; (2) DHEA increased 25-OH-cholesterol-stimulated pregnenolone release but not when 25-OH-cholesterol was combined with trilostane; (3) DHEA increased the K(m) of 11beta-hydroxylase but not P450scc; (4) DHEA affected the expression levels of StAR protein but not of P450scc. These results suggest that DHEA acts directly on rat ZFR cells to diminish corticosterone secretion by inhibition within the post-cAMP pathway, by inhibiting steroidogenic enzymes downstream from P450scc and by inhibiting StAR expression.
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PMID:Effects of dehydroepiandrosterone on corticosterone release in rat zona fasciculata-reticularis cells. 1461 81

Validation for canine serum of 2 commercially available time-resolved fluoroimmunoassays (TR-FIAs) designed for analysis of cortisol and free thyroxine (fT4) in human serum was carried out. Included was the study of interference by hemolysis, lipemia, and bilirubinemia. With the dissociation enhancement lanthanide fluoroimmunoassay kits, the intra-assay coefficient of variation (CV) ranged from 6.4% to 8.7% for cortisol and from 5.3% to 9.8% for fT4; the interassay CVs ranged from 5.8% to 10.8% and from 3.9% to 14.1%, respectively. Accuracy was evaluated by comparing cortisol and fT4 results obtained with TR-FIA and those obtained with a validated enzyme-linked immunosorbent assay (ELISA) and an equilibrium dialysis (ED) assay, respectively. The regression equations obtained were y = 0.57x + 1.18 (r2 = 0.90) for cortisol and y = 0.87x + 0.82 (r2 = 0.93) for fT4. The limits of detection for cortisol and fT4 were 4.84 nmol/L and 2.68 pmol/L, respectively. The results of adrenocorticotropin-stimulation and dexamethasone-suppression tests were similar to those published previously; likewise, serial dilution of a canine serum sample with a high cortisol content demonstrated that the TR-FIA was immunologically specific. Serial dilution of a serum sample with a high fT4 concentration showed a methodologic bias, a dependence on serum binding capacity, which indicates that the results obtained with this method should be interpreted with caution. Finally, hemolysis and lipemia significantly interfered with cortisol and fT4 measurements, whereas bilirubinemia did not affect the results.
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PMID:Cortisol and free thyroxine determination by time-resolved fluorometry in canine serum. 1518 53

The metabolic syndrome has several similarities with Cushing's syndrome (impaired glucose tolerance, hypertension, dyslipidemia, central obesity) suggesting that abnormalities in the regulation of the hypothalamic-pituitary-adrenal axis may have a link with the metabolic syndrome. Several studies suggested an association between the clinical signs of the metabolic syndrome and the increased hypothalamic-pituitary-adrenal axis activity based on increased cortisol concentration at 09.00 a.m. and increased cortisol response to corticotropin. According to the Barker hypothesis the fetal malnutrition could determine adult cardiovascular diseases (coronary heart disease, hypertension), some endocrine and metabolic disorders (obesity, type 2 diabetes and hyperlipidemia). The suggested mechanism of the phenomenon is that the suboptimal fetal nutrition results in glucocorticoid overproduction. The 11beta-hydroxysteroid dehydrogenase (converts biological inactive cortisone to cortisol and vice versa) is an important enzyme in cortisol metabolism. The increased expression of 11beta-hydroxysteroid dehydrogenase type 1 in fat tissue could lead to central obesity and impaired glucose tolerance. The hypothesis that increased corticotropin-releasing hormone production drives the overactive hypothalamo-pituitary-adrenal axis was not proven. Further investigations are needed to identify additional pathogenetic factors and to find new therapeutic possibilities.
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PMID:[Correlations between the hypothalamo-pituitary-adrenal axis and the metabolic syndrome]. 1572 52

Systemic aldosterone plays an important role in the development of the microvascular disease and glomerular damage of the kidney in patients with diabetes mellitus and hyperlipidemia. Here, we investigated the possibility of local production of aldosterone in the kidney, using human primary glomerular mesangial cells. These cells produced both pregnenolone and aldosterone measured by specific radioimmunoassay and/or gas chromatography/mass spectrometry (GC/MS) methods. The production of both steroids was significantly stimulated by treatment with LDL, while angiotensin II had a synergistic effect. Adrenocorticotropic hormone (ACTH) and (Bu)2cAMP, on the other hand, failed to stimulate aldosterone production by these cells, suggesting that the local production of this steroid by mesangial cells is regulated differently from that of adrenal zona glomerulosa cells. Mesangial cells expressed the mRNA of the LDL receptor and steroidogenic enzymes, such as P450scc, 3beta-hydroxysteroid dehydrogenase (3beta-HSD), 21-hydroxylase and CYP11B2. Mesangial cells also expressed mRNA of the mineralocorticoid receptor (MR), and LDL stimulated its abundance by three-fold, while spironolactone, a completive antagonist of aldosterone, completely abolished this LDL effect. Since MR is a known mineralocorticoid-responsive gene as well as an intracellular receptor molecule for this steroid, these results suggest that locally produced aldosterone is biologically active, stimulating the transcription rates of the mineralocorticoid-responsive genes by activating the MR in mesangial cells. These pieces of evidence indicate that human mesangial cells are an aldosterone-producing tissue in which LDL plays a major regulatory role. Therefore, human renal mesangial endocrine system may contribute to local aldosterone concentrations and effects in the renal glomerulus independently of the systemic renin--angiotensin--aldosterone system and may participate in the development and progression of glomerular damage in several pathologic conditions.
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PMID:Human renal mesangial cells produce aldosterone in response to low-density lipoprotein (LDL). 1599 78

Studies in our laboratory and elsewhere have demonstrated numerous abnormalities of steroid and polypeptide hormone secretion in obesity: hyperestrogenemia and hypogonadotropic hypogonadism in obese men; diminished SHBG levels in both sexes; elevated free testosterone and free estradiol in obese women; PCOS-like gonadotropin and sex-hormone abnormalities in obese women; elevated serum insulin in both sexes; blunted stimulability of prolactin, growth hormone, and vasopressin in both sexes; and elevated basal levels and blunted stimulability and suppressibility of beta-endorphin in both sexes. All of these abnormalities have been clearly shown to be partly or completely reversible with weight loss, with the exception of the endorphin abnormalities. In that area, four out of the five studies reported show no reversibility with weight loss. Reversibility of nearly all the hormonal abnormalities of obesity (i.e., all but the hyperendorphinemia) by weight loss suggests that none of them is causative of obesity. Nevertheless, some of the reversible abnormalities may secondarily amplify the morbidity associated with obesity: the hyperinsulinemia may be related to the increased risk of hypertension, hyperlipidemia, coronary disease, and Type II diabetes; the elevated levels of free estradiol in obese women may be related to their increased risk of breast and endometrial cancer. The role of hyperendorphinemia in obesity clearly requires further investigation, since it is the only observed hormonal abnormality that appears to be non-reversible by weight loss, and also since there seems to be increased sensitivity to beta-endorphin in obesity. The possibility that endorphin abnormalities may be causal in obesity cannot be ruled out.
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PMID:A perspective on the hormonal abnormalities of obesity: are they cause or effect? 1635 9


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