Fever-Producing Steroids of Endogenous Origin in Man

Kappas, Attallah

doi:10.1001/archinte.1960.00270170039005

Cited by 40 publications

(8 citation statements)

References 8 publications

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“…In contrast, /3-orientation of the carbon 11 oxygen substituent in neutral steroids has little effect on fever-producing activity (4). The two dihydroxy bile acids found to have weak and irregular thermogenic action (ursodeoxycholic and hyodeoxycholic acids) have additional hydroxyl groups in the 7,/ and 6a positions, respectively, and although the equatorial orientation of both hydroxyls may account for incomplete suppression of fever-producing action, individual differences in response to injected steroids, noted previously (6), may be of some importance in determining the consistency of the pyrogenic reaction to these compounds.…”

Section: Methods and Resultsmentioning

confidence: 91%

“…The study was prompted by the structural similarity between these acidic steroids and the pyrogenic neutral steroids described previously (2)(3)(4)(5)(6)(7). In addition, it seemed important to establish whether the large quantities of steroid acids formed during the metabolism of cholesterol could serve as a source of endogenous compounds having fever-producing action in man.…”

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confidence: 99%

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Pyrogenic and Inflammatory Properties of Certain Bile Acids in Man*

Palmer¹,

Glickman²,

Kappas³

1962

J. Clin. Invest.

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This is a report on the pyrogenic and inflammatory properties of certain bile acids in man. The study was prompted by the structural similarity between these acidic steroids and the pyrogenic neutral steroids described previously (2-7). In addition, it seemed important to establish whether the large quantities of steroid acids formed during the metabolism of cholesterol could serve as a source of endogenous compounds having fever-producing action in man. METHODS AND RESULTSNineteen bile acids and derivatives were examined for fever-producing activity after their intramuscular administration to adult volunteer hospital patients. Lithocholic acid was repeatedly recrystallized to insure purity. The glycine, taurine, and acetyl derivatives of lithocholic acid were synthesized and purified in these laboratories; the other compounds were obtained commercially and used without additional purification. All bile acids were dissolved in propylene glycol, in concentrations of 12.5 and 25.0 mg per ml, and because of their acidity these solutions were neutralized with dilute base. The general details of the study, including precautions taken to exclude bacterial pyrogen contamination, were similar to those described in a previous report (3). The compounds examined, together with the incidence of pyrogenic responses which followed their injection, are listed below.

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Section: Methods and Resultsmentioning

confidence: 91%

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confidence: 99%

Pyrogenic and Inflammatory Properties of Certain Bile Acids in Man*

Palmer¹,

Glickman²,

Kappas³

1962

J. Clin. Invest.

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“…Therefore, although the injected mass of corticosterone metabolite was probably greater than the mass of aldosterone metabolite, the reabsorption of tritiated material represented in both cases an enterohepatic shunt of relatively large masses of metabolite. The physiologi¬ cal significance of this shunt is obscure, although there is some evidence to suggest that tetrahydro-derivatives of gonadal and adrenocortical steroids may act as regu¬ lators of body temperature and plasma cholesterol concentrations in man (Kappas, Soybel, Glickman & Fukushima, 1960;Hellman et al 1959).…”

Section: (B) \L2-3h\aldosterone-injected Birdsmentioning

confidence: 99%

The Distribution and Metabolism of Labelled Corticosteroids in the Duck (Anas Platyrhynchos)

Helton¹,

Holmes²

1973

Journal of Endocrinology

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After the injection of [1,2-3H]corticosterone into ducks, no unaltered free [1,2-3H]corticosterone was found in either bile, gut contents or cloacal fluid. All the [1,2-3H]corticosterone metabolites in cloacal fluid had similar chromatographic mobilities. A portion of these metabolites was steroid ester sulphate but enzymic hydrolysis suggested that only a small fraction of the sulphate was conjugated to [1,2-3H]corticosterone. The amount of ester sulphate in samples of cloacal fluid, however, was highly variable.After the injection of [1,2-3H]aldosterone one-fifth of the total radioactivity in urine was free [1,2-3H]aldosterone but none was found in the bile and gut contents. Chromatographic purification of the [1,2-3H]aldosterone metabolites in cloacal fluid showed two significant peaks and both peaks contained steroid ester sulphates. Enzymic hydrolysis of the tritiated material showed that each peak also contained a glucuronide of [1,2-3H]aldosterone.The effect of the entero-hepatic circulation on the excretion of tritiated metabolites by the kidney was also examined. Diversion of bile from the duodenum prevented the entry of radioactive material into the gut. The reduced reabsorption of tritiated corticosterone and tritiated aldosterone metabolites from the gut, however, did not affect the amount of tritium excreted by the kidneys. In the case of both hormones, some of the reabsorbed metabolite which had been extracted by the liver was released and re-entered the peripheral blood via the hepatic circulation. The stress of surgery in both the control birds and the birds with bile catheters caused the distribution of [1,2-3H]corticosterone and the tritiated corticosterone metabolites to change; a significantly smaller percentage of the injected radioactivity was recovered from the tissues and excretory fluids. This response to stress was not observed in the [1,2-3H]aldosterone injected birds.When partially purified metabolites of [1,2-2-3H]corticosterone and [ 1, 2\ x=r eq-\ 3H]aldosterone were injected into the lumen of the gut, the rate of uptake of the tritiated corticosterone metabolites was higher than that of the tritiated aldosterone metabolites. But, when the metabolites of [ 1, 2\ x=r eq-\ 3H]corticosterone and [1,2-3H]aldosterone were injected intravenously, and the rate of the intestinal reabsorption of the metabolites was not limiting, the rates of tritium excretion by the kidneys were the same. The volumes of distribution and metabolic clearance rates of the partially purified [1,2-3H]corticosterone and [1,2-3H]aldosterone metabolites were significantly different from one another and the metabolites could be readily distinguished physiologically as well as chromatographically. The pattern of distribution and the disappearance from plasma of i.v. administered synthetic [ 1, 2\ x=req-\ 3H]corticosterone-21-SO4 was also distinguishable from the naturally occurring metabolites of [1,2-3H]corticosterone.

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“…Received for publication 5 June 1967 and in revised form 11 September 1967. Yale University School of Tests with etiocholanolone and with steroids closely related in structure indicate that these agents produce fever only in man (4). Unlike fever induced by bacterial endotoxin, which develops within 1-11/ hr after intravenous injection, there is a delay of 416 hr before the onset of steroid-induced fever, which may then last for 12 hr or more (2).…”

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confidence: 99%

“…Unlike fever induced by bacterial endotoxin, which develops within 1-11/ hr after intravenous injection, there is a delay of 416 hr before the onset of steroid-induced fever, which may then last for 12 hr or more (2). Pyrogenic activity of various steroids is related to their particular structural features (5), and appears to depend on a 5,8-configuration (1).…”

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confidence: 99%