Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Seven males with liver cirrhosis associated with hepatitis and one with schistosomal liver fibrosis were studied for hypophyseal gonadal dysfunction and compared to six age matched controls. Cirrhotics as a group had higher serum 17 beta estradiol levels (22.1 +/- 6.3 vs 7.8 +/- 0.8 pg/ml, p less than 0.05) which did not rise after four days of human chorionic gonadotropin (hCG) stimulation. Conversely, there was an adequate rise in serum testosterone level after hCG stimulation (332.8 +/- 99.7 ng/dl baseline to 887.6 +/- 67.1 ng/dl, p less than 0.01). Compared to the controls, cirrhotics had lower baseline serum follicle stimulating hormone (FSH) (3.6 +/- 1.7 vs. 10.2 +/- 1.5 mIu/ml, p less than 0.02) and higher serum prolactin (13.5 +/- 2.5 vs. 6.8 +/- 1.0 ng/ml, p less than 0.05). Pituitary dynamic function testing in cirrhotics revealed blunted response of luteinizing hormone (LH) and FSH, to luteinizing hormone releasing hormone (LHRH) in four out of eight subjects tested. We conclude that the mechanism of hypogonadism in non-alcoholic cirrhosis is mostly hypogonadotropic in origin rather than primary gonadal injury which is common in alcoholic cirrhosis.
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PMID:Hypophyseal-gonadal dysfunction in men with non-alcoholic liver cirrhosis. 392 49

Impaired ability to excrete a water load occurs in a substantial number of patients with advanced cirrhosis and in animals with experimental cirrhosis. The nonosmotic stimulation of arginine vasopressin release from the pituitary has been implicated as an important factor in the abnormal water excretion in patients and animals with cirrhosis. In this study, arginine vasopressin hypothalamic gene expression was studied in cirrhotic rats. Cirrhosis was induced by a combination of phenobarbital treatment in drinking water and weekly intragastric administration of carbon tetrachloride for 13 to 15 wk. Severe cirrhosis was confirmed by morphological analysis and the presence of ascites. Plasma arginine vasopressin was also significantly higher in rats with cirrhosis (control = 1.77 +/- 0.16 and cirrhotic rats = 4.14 +/- 0.62 pg/ml, n = 9, p < 0.002). Hypothalamic arginine vasopressin messenger RNA was also significantly higher in cirrhotic rats (control = 762.1 +/- 132.3 and cirrhotic rats = 1,834.2 +/- 271.9 pg/hypothalamus, n = 9, p < 0.005). Pituitary arginine vasopressin content was significantly lowered in cirrhotic rats (control = 3.69 +/- 0.98 and cirrhotic rats = 1.57 +/- 0.09 micrograms/pituitary, n = 9, p < 0.05). No difference was seen in hypothalamic arginine vasopressin content between the two groups (control = 4.64 +/- 0.34 and cirrhotic rats = 4.23 +/- 0.33 ng/hypothalamus, n = 9, NS). Oxytocin messenger RNA in the hypothalamus was also not significantly different between the two groups (control = 8.61 +/- 0.68 and cirrhotic rats = 9.33 +/- 0.65 unit of density, n = 9, NS).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Vasopressin gene expression in rats with experimental cirrhosis. 842 35

Selective iron deposition in the zona glomerulosa of the adrenal cortex is observed in hemochromatosis. Hypoaldosteronism should be excluded before starting venesection, to avoid long-term volume depletion. We evaluated the aldosterone status in patients with hemochromatosis. As other endocrine organs can be affected by the disease as well, we simultaneously evaluated anterior pituitary, gonadal, thyroid and pancreatic beta-cell activity. Nine patients with hereditary or acquired hemochromatosis and highly increased plasma ferritin levels were investigated. In patients, liver cirrhosis had been confirmed histologically. Five patients complained of sexual dysfunction, and one had impaired glucose tolerance. Plasma aldosterone (PA) and renin activity (PRA) were measured after a period of normal (100 mmol/day) and low (10 mmol/day) sodium intake. A combined anterior pituitary function test and a glucagon stimulation test were undertaken to evaluate other endocrine functions. Both PA and PRA levels were decreased in one patient with liver cirrhosis, who also presented attenuated cortisol, prolactin and gonadotrophin secretion. No patients had signs of primary hypoaldosteronism with hyperreninemia. Hypogonadotropic hypogonadism was observed in 3 males and 1 female. Pituitary ACTH reserve was impaired in 2, GH and prolactin response in 1, and thyroid function in none of the patients. Glucagon-stimulated plasma C-peptide was impaired in one patient. In conclusion, primary aldosterone deficiency was not observed in patients with severe iron overload. Hyporeninemic hypoaldosteronism was found in one patient who also presented other endocrinopathies. Hypogonadotropic hypogonadism is the most frequent endocrine abnormality in hemochromatosis.
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PMID:Mineralocorticoid status and endocrine dysfunction in severe hemochromatosis. 1040 11

The Hypothalamic-Pituitary-Adrenal (HPA) axis has an important role in maintaining the physiological homeostasis in relation to external and internal stimuli. The HPA axis dysfunctions were extensively studied in neuroendocrine disorders such as depression and chronic fatigue syndrome but less so in hepatic cholestasis, cirrhosis or other liver diseases. The HPA axis controls many functions of the liver through neuroendocrine forward signaling pathways as well as negative feedback mechanisms, in health and disease. This review describes cell and molecular mechanisms of liver and HPA axis physiology and pathology. Evidence is presented from clinical and experimental model studies, demonstrating that dysfunctions of HPA axis are correlated with liver cholestatic disorders. The functional interactions of HPA axis with the liver and immune system in cases of bacterial and viral infections are also discussed. Proinflammatory cytokines stimulate glucocorticoid (GC) release by adrenals but they also inhibit bile acid (BA) efflux from liver. Chronic hepatic inflammation leads to cholestasis and impaired GC metabolism in the liver, so that HPA axis becomes depressed. Recently discovered interactions of GC with self-oscillating transcription factors that generate circadian rhythms of gene expression in brain and liver, in the context of GC replacement therapies, are also outlined.
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PMID:Hypothalamus-Pituitary-Adrenal Dysfunction in Cholestatic Liver Disease. 3048 16

Pituitary adenylate cyclase-activating peptide (PACAP) is a ubiquitous neuropeptide with diverse functions throughout the organism. Most abundantly investigated for its role in several neurological disorders as well as in circadian rhythms, other fields of medicine, including cardiology, have recently shown interest in the role of PACAP and its potential as a biomarker. Timely diagnosis and treatment of cirrhosis and its complications is a considerable challenge for health services world-wide and development of new areas of research is warranted. Direct and indirect evidence exists of PACAP involvement in the cascade of pathological events and processes ultimately leading to cirrhosis and its complications, but its exact role remains to be determined. Studies have documented PACAP involvement in immune function, metabolism, local vasoconstriction and dilatation and systemic vascular decompensation and there is ongoing research of a possible role in liver reperfusion injury. Considering these reports, PACAP could theoretically exude influence on the disease course of cirrhosis through the hypothalamus-pituitary-adrenal axis, chronic inflammation, fibrogenesis, vasodilation and reduced vascular resistance. The paucity of literature on the specific topic of PACAP and cirrhosis reflects complex mechanisms and difficulty in accurate measurements and sample taking. This does not detract from the need to further characterize and elucidate the role PACAP plays in the underdiagnosed and undertreated condition of cirrhosis.
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PMID:Pituitary adenylate cyclase-activating peptide: Potential roles in the pathophysiology and complications of cirrhosis. 3265 67