Metabolism of cortisol in anorexia nervosa

1990 ◽  
Vol 122 (6) ◽  
pp. 753-758 ◽  
Author(s):  
H. Vierhapper ◽  
A. Kiss ◽  
P. Nowotny ◽  
S. Wiesnagrotzki ◽  
C. Monder ◽  
...  
Keyword(s):  
Anorexia Nervosa ◽  
Urinary Excretion ◽  
Plasma Concentrations ◽  
Adrenocortical Function ◽  
Acth Stimulation ◽  
Healthy Women ◽  
Rate Limiting Step ◽  
Enhanced Secretion ◽  
Excretion Rates ◽  
Steroid Excretion

Abstract. In patients with anorexia nervosa 24-h mean plasma concentration of cortisol were 0.44± 0.09 μmol/l (normal < 0.28 μmol/l). Following stimulation by ACTH (1–24) urinary excretion rates of cortisol were stimulated from 0.22 ± 0.08 to 4.85 ± 2.78 μmol/24 h. Similarly, plasma concentrations of the glucocorticoid metabolite, tetrahydrocortisone, increased from 23.3 ± 9.0 to 47.3 ± 30.2 nmol/l; urinary excretion rates of tetrahydrocortisone increased from 3.61 ± 0.90 to 8.40 ± 1.72 μmol/24 h. The relative share of the sulphate, glucuronide and free fractions of tetrahydrocortisone in the patients' urine did not indicate any defect in metabolization of this steroid metabolite. Excretion rates of the four glucocorticoid tetrahydro-metabolites, tetrahydrocortisone, allotetrahydrocortisone, tetrahydrocortisol, and allo-tetrahydrocortisol, expressed as percent of total steroid excretion, were similar in patients with anorexia and in healthy women under basal conditions (24 ± 6 vs 23 ± 6%) and during stimulation by ACTH (1–24) (36 ± 10 vs 45 ± 6%). The share of the two androgen metabolites, androsterone and etiocholanolone, was 24 ± 5% of total steroid excretion (basal; healthy women: 27 ± 8%) and 13 ± 2% (ACTH stimulation; healthy women: 12 ± 4%) in patients with anorexia nervosa. Thus, analysis of urinary steroid excretion rates did not indicate a shift in adrenocortical function. The results confirmed enhanced secretion of cortisol in patients with anorexia nervosa under basal conditions and during/following stimulation by ACTH. The ACTH-induced increase in the concentrations of the tetrahydro-glucocorticoid metabolites in urine was less pronounced than that of cortisol. The data strongly suggest a rate-limiting step in the transformation of cortisol into its main metabolites, most likely an impaired reduction of the double bond in positions C4/C5.

Effects of thyroparathyroidectomy, parathyroid hormone, and PTHrP on kidneys of ovine fetuses

1993 ◽  
Vol 264 (1) ◽  
pp. E37-E44 ◽  
Author(s):  
R. J. MacIsaac ◽  
R. S. Horne ◽  
I. W. Caple ◽  
T. J. Martin ◽  
E. M. Wintour
Keyword(s):  
Parathyroid Hormone ◽  
Urinary Excretion ◽  
Excretion Rate ◽  
Plasma Concentrations ◽  
Free Water ◽  
Total Calcium ◽  
Fetal Plasma ◽  
Parathyroid Hormone Related Protein ◽  
Fetal Urine ◽  
Excretion Rates

The fetal parathyroid glands and parathyroid hormone-related protein (PTHrP) have been shown to be important regulators of fetal calcium metabolism through their actions on the placenta and bone. This study examined the effects of fetal thyroparathyroidectomy (with thyroxine replacement) and exogenous infusion of human parathyroid hormone [PTH-(1–34)], PTHrP-(1–34), and PTHrP-(1–141) on the urinary excretion of calcium in chronically cannulated ovine fetuses during the last one-fifth of gestation. Fetal plasma total and ionized calcium concentrations were significantly lower in thyroparathyroidectomized (TxPTx) fetuses when compared with intact fetuses, but there were no significant differences in urinary excretion rates of total calcium. However, TxPTx produced a significant increase in the fractional excretion rate of total calcium and a significant decrease in the excretion of adenosine 3',5'-cyclic monophosphate (cAMP) compared with intact fetuses. Infusions of PTH-(1–34), PTHrP-(1–34), and PTHrP-(1–141) into the jugular vein of TxPTx fetuses (n = 5) at the rate of 1 nmol/h for 2 h, after a 1-nmol loading dose, significantly decreased the excretion rate of total calcium and increased the excretion rate of cAMP in fetal urine. Infusions of all three peptides resulted in significant increases in the concentration of total calcium in fetal plasma but had no effect on the plasma concentrations or urinary excretion rates of phosphate. Infusion of either PTH-(1–34), PTHrP-(1–34), or PTHrP-(1–141) also resulted in an increase in fetal urine osmolality and pH and a decrease in free water clearance in TxPTx fetuses.(ABSTRACT TRUNCATED AT 250 WORDS)

Moderate dieting causes 5-HT 2C receptor supersensitivity

1996 ◽  
Vol 26 (6) ◽  
pp. 1155-1159 ◽  
Author(s):  
P. J. Cowen ◽  
E. M. Clifford ◽  
A. E. S. Walsh ◽  
C. Williams ◽  
C. G. Fairburn
Keyword(s):  
Eating Disorders ◽  
Anorexia Nervosa ◽  
Bulimia Nervosa ◽  
Receptor Agonist ◽  
Plasma Concentrations ◽  
Developed Countries ◽  
Receptor Supersensitivity ◽  
Healthy Women ◽  
Prolactin Response

SynopsisDieting is a widespread behaviour in developed countries, which in predisposed individuals can lead to the development of clinical eating disorders such as bulimia nervosa and anorexia nervosa. We studied the effect of moderate dieting in healthy women on the prolactin response to the serotonin (5-HT) receptor agonist, m-chlorophenylpiperazine (mCPP), a measure of the sensitivity of post-synaptic 5-HT2C receptors. Dieting significantly increased the prolactin response to mCPP and lowered plasma concentrations of the 5-HT precursor, tryptophan. We propose that dieting in women is associated with the development of functional supersensitivity of 5-HT2C receptors, probably in response to lowered levels of brain 5-HT. Alterations in brain 5-HT neurotransmission could play a part in dieting-induced dysregulation of eating and the development of clinical eating disorders in predisposed individuals.

Renal handling of circulating nitrates in anesthetized dogs

1998 ◽  
Vol 275 (1) ◽  
pp. F68-F73 ◽  
Author(s):  
Murrell Godfrey ◽  
Dewan S. A. Majid
Keyword(s):  
Urinary Excretion ◽  
Plasma Concentrations ◽  
Biological Tissues ◽  
The Body ◽  
No Production ◽  
Renal Handling ◽  
Enzymatic Reduction ◽  
Anesthetized Dogs ◽  
Excretion Rates ◽  
Synthase Inhibitor

Nitric oxide (NO) is rapidly oxidized to nitrite ([Formula: see text]) and then to nitrate ([Formula: see text]) in biological tissues. Although urinary excretion rates of[Formula: see text] are often used as an index of NO production in the body, very little is known regarding the kidney’s ability to excrete circulating [Formula: see text]. We have evaluated the renal responses to systemic administration of sodium nitrate (NaNO3) in eight anesthetized dogs treated with the NO synthase inhibitor, nitro-l-arginine (NLA; 50 μg ⋅ kg−1 ⋅ min−1), intrarenally to minimize renal production of NO. Urinary and plasma concentrations of[Formula: see text]/[Formula: see text](NOX) were determined by the Greiss reaction after enzymatic reduction of [Formula: see text] to[Formula: see text]. NLA treatment alone resulted in reductions in urinary NOX excretion rates (UNOXV, 1.13 ± 0.2 to 0.53 ± 0.1 nmol ⋅ min−1 ⋅ g−1) and an increase in fractional reabsorption of NOX (FRNOX, 93.8 ± 0.6 to 97 ± 0.6%) without changes in arterial plasma concentrations (ANOX, 18.7 ± 1.4 to 21.2 ± 3.7 μM). Administration of NaNO3(10, 20, 30, and 40 μg ⋅ kg−1 ⋅ min−1) resulted in dose-dependent increases in ANOX (34.5 ± 8.0, 46.4 ± 7.3, 60.7 ± 6.3, and 78.1 ± 6.3 μM), UNOXV (1.8 ± 0.7, 4.2 ± 1.8, 7.0 ± 2.0, and 11.4 ± 3.3 nmol ⋅ min−1 ⋅ g−1), and decreases in FRNOX (93.8 ± 2.3, 90.3 ± 3.5, 88.6 ± 3.2, and 84.6 ± 3.5%). Absolute net tubular reabsorption of [Formula: see text] showed a linear relationship with filtered loads, with no evidence of a transport maximum. These data show that, in the absence of additions from intrarenal sources, urinary excretion rates of nitrate increases progressively in response to increases in its circulating levels without exhibiting a transport maximum but with progressive decreases in fractional reabsorption.

scholarly journals Pharmacokinetics of recombinant human soluble thrombomodulin in disseminated intravascular coagulation patients with acute renal dysfunction

2017 ◽  
Vol 117 (05) ◽  
pp. 851-859 ◽  
Author(s):  
Shigeki Kushimoto ◽  
Eizo Watanabe ◽  
Koji Goto ◽  
Yasushi Suzuki ◽  
Toru Kotani ◽  
...  
Keyword(s):  
Urinary Excretion ◽  
Renal Dysfunction ◽  
Disseminated Intravascular Coagulation ◽  
Plasma Concentrations ◽  
Acute Renal Dysfunction ◽  
Soluble Thrombomodulin ◽  
Intravascular Coagulation ◽  
Renal Functions ◽  
Excretion Rates ◽  
Recombinant Human Soluble Thrombomodulin

SummaryRecombinant human soluble thrombomodulin (ART-123) is a novel anticoagulant for patients with disseminated intravascular coagulation (DIC). It is widely used in clinical settings throughout Japan. Furthermore, a global Phase 3 study is currently being conducted. In healthy subjects, ART-123 is excreted mainly via the kidneys. Therefore, ART-123 dose decrease was recommended in DIC patients with severe renal dysfunction. However, the pharmacokinetics of ART-123 in DIC patients with severe acute renal dysfunction has not been elucidated. In an open-label, multicentre, prospective, clinical pharmacological study, we investigated the pharmacokinetics and safety of ART-123 upon repeated administration to DIC patients. ART-123 was administered to patients at a dose of 130 or 380 U/kg/day for six consecutive days. Plasma concentrations of ART-123 were measured at 21 time points until eight days after the final administration. Urinary excretion rates during the first 24 hours (h) were calculated. Patient renal functions were evaluated by measuring 24-h creatinine clearance (Ccr). Forty-three patients were enrolled in the present study. The urinary excretion rates of ART-123 correlated closely with 24-h Ccr. Total body clearance of ART-123 was also weakly related with 24-h Ccr. However, the plasma concentrations of ART-123 were not considerably different among patients with different renal function. Two patients had subcutaneous haemorrhage as an adverse event related to ART-123. In conclusion, plasma concentrations of ART-123 may not be different among patients with different renal functions. ART-123 was well tolerated in these patients.

THE EFFECT OF EXOGENOUS CORTICOTROPHIN ON STEROID EXCRETION IN THE NEWBORN

1968 ◽  
Vol 58 (4) ◽  
pp. 655-663 ◽  
Author(s):  
C. Lauritzen ◽  
C. H. L. Shackleton ◽  
F. L. Mitchell
Keyword(s):  
Urinary Excretion ◽  
In Utero ◽  
Early Infancy ◽  
Average Increase ◽  
Acth Stimulation ◽  
Production Ratio ◽  
Before And After ◽  
The Individual ◽  
Steroid Excretion

ABSTRACT The urinary excretion of the individual 3β-hydroxy-Δ5 steroids together with cortisol and the chromatographic bands of material containing its tetrahydrometabolites, have been studied in early infancy before and after stimulation by exogenous corticotrophin (ACTH). The average increase in the excretion of the Δ5 steroids after stimulation is relatively small (less than 185%) compared with the increase in cortisol and its metabolites (greater than 600%) and it is suggested that ACTH stimulation cannot be solely responsible for the formation of the considerable quantities of Δ5 steroids in early infancy and the high Δ5 steroid/cortisol production ratio in utero.

scholarly journals Absorption and metabolism of isothiocyanates formed from broccoli glucosinolates: effects of BMI and daily consumption in a randomised clinical trial

2018 ◽  
Vol 120 (12) ◽  
pp. 1370-1379 ◽  
Author(s):  
Craig S. Charron ◽  
Bryan T. Vinyard ◽  
Sharon A. Ross ◽  
Harold E. Seifried ◽  
Elizabeth H. Jeffery ◽  
...  
Keyword(s):  
Urinary Excretion ◽  
Control Diet ◽  
Plasma Concentrations ◽  
Human Study ◽  
Randomised Clinical Trial ◽  
Preclinical Study ◽  
Daily Consumption ◽  
Anti Cancer ◽  
Median Plasma ◽  
Excretion Rates

AbstractSulphoraphane originates from glucoraphanin in broccoli and is associated with anti-cancer effects. A preclinical study suggested that daily consumption of broccoli may increase the production of sulphoraphane and sulphoraphane metabolites available for absorption. The objective of this study was to determine whether daily broccoli consumption alters the absorption and metabolism of isothiocyanates derived from broccoli glucosinolates. We conducted a randomised cross-over human study (n18) balanced for BMI and glutathioneS-transferaseμ1 (GSTM1) genotype in which subjects consumed a control diet with no broccoli (NB) for 16 d or the same diet with 200 g of cooked broccoli and 20 g of raw daikon radish daily for 15 d (daily broccoli, DB) and 100 g of broccoli and 10 g of daikon radish on day 16. On day 17, all subjects consumed a meal of 200 g of broccoli and 20 g of daikon radish. Plasma and urine were collected for 24 h and analysed for sulphoraphane and metabolites of sulphoraphane and erucin by triple quadrupole tandem MS. For subjects with BMI >26 kg/m2(median), plasma AUC and urinary excretion rates of total metabolites were higher on the NB diet than on the DB diet, whereas for subjects with BMI <26 kg/m2, plasma AUC and urinary excretion rates were higher on the DB diet than on the NB diet. Daily consumption of broccoli interacted with BMI but notGSTM1genotype to affect plasma concentrations and urinary excretion of glucosinolate-derived compounds believed to confer protection against cancer. This trial was registered as NCT02346812.

ADRENOCORTICAL FUNCTION IN A PROTOTHERIAN MAMMAL, TACHYGLOSSUS ACULEATUS (SHAW)

1977 ◽  
Vol 72 (1) ◽  
pp. 41-52 ◽  
Author(s):  
C. SERNIA ◽  
I. R. McDONALD
Keyword(s):  
Plasma Concentrations ◽  
Adrenocortical Function ◽  
Metabolic Clearance ◽  
Production Rates ◽  
Acth Stimulation ◽  
Behavioural Activity ◽  
Constant Rate ◽  
Peripheral Blood Plasma ◽  
High Concentrations ◽  
Tachyglossus Aculeatus

SUMMARY The peripheral plasma concentrations and production rates of corticosterone and cortisol were measured in the conscious, unrestrained echidna (Tachyglossus aculeatus) under basal conditions and during maximal ACTH stimulation. Using Sephadex LH-20 column chromatography and radioligand assay, only cortisol and corticosterone could be detected in the peripheral blood plasma at very low concentrations of 0·07 ± 0·03 (s.e.m.) μg/100 ml and 0·14 ± 0·07 μg/100 ml respectively. Two-hourly sampling over periods of 36–48 h disclosed a diurnal periodicity in the combined plasma concentration of these corticosteroids, the high concentrations corresponding to periods of behavioural activity. Marked, short-term fluctuations in plasma corticosteroid concentration were also observed during periods of more frequent (20 min) sampling. Constant rate i.v. infusion of synthetic ACTH increased the plasma concentrations of both steroids to maximal values of 0·42 ± 0·23 μg cortisol/100 ml and 1·06 ± 0·56 μg corticosterone/100 ml at infusion rates of 1 i.u. ACTH/kg/h. This is approximately 1/160 of the potency of this ACTH in man. The production rates of corticosterone and cortisol, measured by isotope dilution during constant rate i.v. infusion of 3H-labelled tracers, were only 0·35 ± 0·21 and 0·56 ± 0·26 μg/kg/h respectively during saline infusion, and increased to 2·86 ± 3·47 and 2·74 ± 2·07 μg/kg/h during the infusion of 1 i.u. ACTH/kg/h. The metabolic clearance rate of cortisol was greater than that of corticosterone and both were depressed by ACTH. Plasma corticosteroid concentrations were increased after surgery during ether anaesthesia and in sick animals with heavy worm infestation. It is concluded that the adrenal cortex of echidnas responds to ACTH stimulation and stress in a similar way to eutherians, but the level of activity is much lower.

THYROID AND ADRENOMEDULLARY REACTIONS DURING SLEEP DEPRIVATION

1979 ◽  
Vol 90 (2) ◽  
pp. 233-239 ◽  
Author(s):  
Jan Palmblad ◽  
Torbjörn Äkerstedt ◽  
Jan Fröberg ◽  
Arne Melander ◽  
Henning von Schenck
Keyword(s):  
Thyroid Hormone ◽  
Sleep Deprivation ◽  
Urinary Excretion ◽  
Plasma Concentrations ◽  
Young Male ◽  
Serum Concentrations ◽  
Male Volunteers ◽  
Enhanced Secretion ◽  
Noradrenaline And Adrenaline

ABSTRACT The possible influence of a 48 h period of sleep deprivation on the serum concentrations of total and unbound 3,5,3′,5′-thyroxine (T4) and 3,5,3′-triiodothyronine (T3), and of total 3,3′,5′-triiodothyronine (reverse T3, rT3) was studied in 12 young male volunteers. In addition, plasma concentrations of TSH and the urinary excretion of noradrenaline and adrenaline were examined. Both total S-T4, S-T3 and S-rT3, and unbound S-T4 and S-T3 (unbound rT3 was not calculated) were significantly enhanced following sleep deprivation. P-TSH showed a numerical but statistically not significant increase, while the catecholamines remained unaltered. The results suggest that sleep deprivation provokes enhanced secretion of thyroid hormone(s), supposedly via increased secretion of TSH.

STEROID EXCRETION IN ANOREXIA NERVOSA PATIENTS

1979 ◽  
Vol 90 (1) ◽  
pp. 133-138 ◽  
Author(s):  
E. Vanluchene ◽  
W. Aertsens ◽  
D. Vandekerckhove
Keyword(s):  
Anorexia Nervosa ◽  
Urinary Excretion ◽  
Metabolic Abnormalities ◽  
Steroid Excretion

ABSTRACT Seven anorexia nervosa (A. N.) patients had reduced urinary excretion values of tetrahydrocortisone (THE), androsterone (A) and 5α-tetrahydrocortisol (5α-THF). THE to tetrahydrocortisol (THF), A to aetiocholanolone (Ae) and 5α-THF to THF ratios were all significantly reduced. Six A. N. patients had oral metyrapone tests with quantitatively normal but delayed urinary 3α,17α,21-trihydroxy-5β-pregnan-20-one (THS) response. The steroid determinations were done by capillary gaschromatography, which proves to be of value in the study of the above mentioned metabolic abnormalities.

Serotoninergic regulation of corticosterone secretion in domestic fowl

1987 ◽  
Vol 113 (2) ◽  
pp. 159-165 ◽  
Author(s):  
A. Cheung ◽  
T. R. Hall ◽  
S. Harvey
Keyword(s):  
Domestic Fowl ◽  
Serotonin Receptor ◽  
Plasma Concentrations ◽  
Adrenocortical Function ◽  
Serotoninergic System ◽  
Acth Stimulation ◽  
Corticosterone Secretion ◽  
Corticosterone Release ◽  
Adrenal Corticosterone

ABSTRACT The effects of serotoninergic drugs on adrenocortical function in domestic fowl were examined. Administration of the serotonin receptor agonist 2-(1-piperazinyl)quinoline maleate (quipazine), an inhibitor of serotonin metabolism, N-methyl-N-2-propynylbenzylamine HCl (pargyline), as well as serotonin itself, all increased plasma concentrations of corticosterone. The maximum responses to serotonin and quipazine occurred 1 h after treatment. The quipazine-stimulated response was partly prevented by the serotonin antagonist cyproheptadine. Cockerels pretreated with dexamethasone, a synthetic steroid known to inhibit pituitary ACTH release, showed attenuated responses to subsequent quipazine, pargyline or serotonin injection. Serotonin, quipazine and cyproheptadine did not affect corticosterone release directly from the adrenal gland incubated in vitro, nor did they affect adrenal responsiveness to ACTH stimulation. The neurotoxin 5,6-dihydroxytryptamine injected into day-old chicks decreased plasma concentrations of corticosterone for up to 7 days after treatment, with corresponding decreases in the hypothalamic concentration of serotonin, but not dopamine or noradrenaline concentrations. These results show that adrenal corticosterone secretion is regulated by a central serotoninergic system, probably acting on the hypothalamo-pituitary-adrenal axis. J. Endocr. (1987) 113,159–165

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