Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: UMLS:C0020473 (hyperlipidemia)
15,891 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

Male and female, young (2 months old) and mature (10 months old), obese and nonobese, spontaneously hypertensive rats (SHR) were treated with dexamethasone, 5 micrograms/rat and 10 micrograms/rat, respectively, subcutaneously (SC) 2 times daily for 5 months. Steroid treatment stilled the voracious appetite of the obese SHR, and the massively obese, mature animals were reduced to almost normal size. The young, steroid-treated, obese SHR did not develop their genetically programmed corpulency. The untreated, young and mature, obese SHR ate voraciously, became massively obese, and developed their characteristic Cushing's disease-like spectrum of degenerative changes, eg, hypertension, hyperlipidemia, hyperglycemia, muscle wasting, kidney stones, thin skin, and accelerated aging. The blood pressure of the steroid-treated animals was lowered concomitant with reduced levels of circulating ACTH, beta endorphin, insulin, triglycerides, and cholesterol. Dexamethasone caused hyperlipidemia, hyperglycemia, and increased BUN levels in young obese and nonobese SHR only. The mature obese SHR had giant-sized thymus glands that were further enlarged with steroid treatment; dexamethasone was thymolytic in young, obese and nonobese SHR. Dexamethasone caused severe reduction of pituitary and adrenal gland size, simulating the condition of hypophysectomy. These findings demonstrate that dexamethasone suppression of the pituitary-adrenal axis palliates and prevents the spontaneous development of Cushingoid degenerative changes in these genetically obese and hypertensive rats.
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PMID:Dexamethasone suppression of cushingoid degenerative changes in obese spontaneously hypertensive rats (SHR). 631 58

Pituitary and adrenal glands removed from male and female spontaneously hypertensive (SH) rat donors with high blood pressure were implanted in normotensive, Sprague-Dawley (S-D) recipients which had been hypophysectomized or adrenalectomized. The transplants were accepted readily and after 90 days the animals were necropsied. Maintenance of organs and body weights suggested that the pituitary glands of SH rats have an adequate content of growth hormone but there may be an intrinsic deficiency of gonadotrophic hormones in this strain. The blood pressure of the hypophysectomized and adrenalectomized recipients was well maintained, particularly by the Sh-rat adrenal transplants, but the blood pressure of the recipients did not become abnormally elevated. SH-rat pituitary and adrenal glands caused fatty infiltration of the liver and hyperlipidaemia indicative of a lipotrophic factor in the SH rat strain. The histopathological changes in the transplanted pituitary and adrenal glands, and in intact pituitary and adrenal glands of the recipients, suggested that SH-rat pituitary glands secrete extra quantities of ACTH, that the pituitary-adrenal axis of this strain is extra sensitive to stressful stimuli, and that the spectrum of adrenal steroids secreted by this strain may be different from that of most normotensive strains.
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PMID:Transplantation of pituitary and adrenal glands of spontaneously hypertensive rats into hypophysectomized or adrenalectomized, normotensive Sprague-Dawley rats. 742 92

Lipid metabolism was studied in 21 horses with hyperadrenocorticism. To be included in the study, horses had to have histologic evidence of a pars intermedia adenoma found at necropsy (n = 9), a baseline ACTH concentration greater than 400 pg/ml (n = 6), or a plasma cortisol concentration 2 hours after i.v. administration of 25 IU of ACTH greater than 413 nmol/L (n = 16). Mean +/- SD baseline plasma cortisol concentration was 338 +/- 261 nmol/L (n = 20), mean +/- SD plasma insulin concentration was 97 +/- 54 microU/ml (n = 15), mean +/- SD plasma beta-hydroxybutyrate concentration was 1.8 +/- 1.2 mg/dl (n = 21), and mean +/- SD plasma nonesterified fatty acids concentration was 6.2 +/- 6.4 mg/dl (n = 21). None of the horses had hyperlipemia. Compared with clinically normal horses, horses with hyperadrenocorticism had increased lipolysis and increased ketogenesis. It was concluded that cortisol cannot be the sole factor contributing to insulin resistance in horses with hyperadrenocorticism.
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PMID:Lipid metabolism in horses with hyperadrenocorticism. 776 7

The mechanisms behind secondary hyperlipidemia in patients with various chronic inflammatory diseases are not known in detail. We have recently demonstrated that ACTH exerts strong hypolipidemic effects in healthy volunteers. To test the clinical relevance of this finding, we administrated ACTH during three weeks to nine hyperlipidemic steroid-treated patients with kidney disease. Before administration of ACTH 1-24, plasma ACTH concentrations were low. Treatment with ACTH led to 20 to 50% reductions in serum concentrations of triglycerides, cholesterol, LDL cholesterol and Apo B as well as of Lp(a). HDL cholesterol and Apo A1 concentrations increased by 10 to 25%. HL activity in postheparin plasma decreased by about 40% and LPL activity, which was initially low, increased by about 140%. The effects of ACTH were similar in kidney transplant recipients and in patients with inflammatory kidney disease. Our results indicate that hyperlipidemia in steroid treated patients with kidney disease may at least partly be due to iatrogenic ACTH deficiency.
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PMID:ACTH lowers serum lipids in steroid-treated hyperlipemic patients with kidney disease. 884 Feb 83

The selective uptake of high density lipoprotein (HDL) cholesteryl ester (CE) by the scavenger receptor class B type I (SR-BI) is well documented. However, the effect of altered HDL composition, such as occurs in hyperlipidemia, on this important process is not known. This study investigated the impact of variable CE and triglyceride (TG) content on selective uptake. CE selective uptake by Y1 and HepG2 cells was strongly affected by modification of either the CE or TG content of HDL. Importantly, TG, like CE, was selectively taken up by a dose-dependent, saturable process in these cells. As shown by ACTH up-regulation and receptor overexpression experiments, SR-BI mediated the selective uptake of both CE and TG. With in vitro modified HDLs of varying CE and TG composition, the selective uptake of CE and TG was dependent on the abundance of each lipid within the HDL particle. Furthermore, total selective uptake (CE + TG) remained constant, indicating that these lipids competed for cellular uptake. These data support a novel mechanism whereby SR-BI binds HDL and mediates the incorporation of a nonspecific portion of the HDL lipid core. In this way, TG directly affects the ability of HDL to donate CE to cells. Processes that raise the TG/CE ratio of HDL will impair the delivery of CE to cells via this receptor and may compromise the efficiency of sterol balancing pathways such as reverse cholesterol transport.
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PMID:Elevated triglyceride content diminishes the capacity of high density lipoprotein to deliver cholesteryl esters via the scavenger receptor class B type I (SR-BI). 1106 53

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

ACTH-independent macronodular adrenal hyperplasia (AIMAH) is a rare cause of Cushing's syndrome. Bilateral adrenalectomy is considered to be a standard therapy for AIMAH, although lifetime replacement of glucocorticoids is necessary after the procedure. This paper describes a subject with AIMAH who underwent unilateral adrenalectomy of the predominantly enlarged gland and subsequently displayed an improvement in insulin resistance and diabetes mellitus, the cardinal symptoms before the operation, concomitant with alleviation of abnormal cortisol secretion. The patient was a 61-year-old man with a body mass index of 25.6 kg/m2. He was diagnosed as having diabetes mellitus, hypertension, and hyperlipidemia at 50 years of age. Eight years after diagnosis, bilateral enlargement of the adrenal glands was revealed by chance upon computed tomography of the abdomen. Typical manifestations of Cushing's syndrome were not demonstrated. Basal levels of serum and urinary cortisol had not increased, although the serum cortisol level displayed no circadian rhythm and no response to the administration of dexamethasone. Despite sulfonylurea treatment, the patient's HbA1C level was as high as 7.6% (normal range 4.3-5.8%). Fasting insulin concentration was increased to 42.6 microU/ml, and the homeostasis model insulin resistance index (HOMA-R) was calculated to be 15.5 (with a normal range of less than 2.5), indicating severe insulin resistance. Unilateral adrenalectomy of the predominantly enlarged gland revealed that the resected gland consisted of multiple nodules of various sizes. Based on endocrinological, radiological, and pathological findings, a diagnosis of AIMAH was made. Ten months after the unilateral adrenalectomy, cortisol circadian rhythms were restored, and serum cortisol concentration was suppressed in response to the administration of low doses of dexamethasone, suggesting an improvement in the cortisol secretory pattern. Levels of HbA1C, fasting insulin, and HOMA-R decreased to 5.7%, 12.7 microU/ml, and 2.2, respectively. An improvement in hyperlipidemia was also observed. Insulin resistance and glucose intolerance are recognized as features of mild hypercortisolism. In the present case, unilateral adrenalectomy was effective in ameliorating insulin resistance and improving glycemic control. Unilateral adrenalectomy might be an alternative therapy for improvement of glucose and lipid metabolism in subjects with AIMAH.
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PMID:Unilateral adrenalectomy improves insulin resistance and diabetes mellitus in a patient with ACTH-independent macronodular adrenal hyperplasia. 1470 42

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

Adult patients with hypopituitarism are treated by the replacement of deficient hormones, although GH has not been substituted until March 2006 in Japan except for clinical trial. This study examines which hormonal status influences the prevalence of vascular risk disorders in hypopituitary adults. A sample of 263 adult patients with hypopituitarism was studied, among whom there were various hormonal status such as no deficiency, treated or untreated deficiency of each pituitary hormone. Analysis of adult patients with hypopituitarism showed that hypertension was more prevalent in the older than in younger patients and in male than in female patients. Hypercholesterolemia and hypertriglyceridemia were more prevalent in patients with TSH deficiency even with thyroxine substitution than those without TSH deficiency. Both obesity and hypertension were less prevalent in patients with treated ACTH deficiency than those without ACTH deficiency. Obesity was more prevalent in patients with treated vasopressin deficiency than those without vasopressin deficiency. These results provide evidence that glucocorticoid substitution in ACTH deficient adults was favorable to prevent obesity and hypertension but that the thyroxine substitution in TSH deficient adults appeared rather insufficient to prevent hyperlipidemia.
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PMID:Hormone replacement therapy and vascular risk disorders in adult hypopituitarism. 1728 80


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