Excretion Of Steroid Metabolites Research Articles

The effect of ibuprofen on the excretion of steroid metabolites

An inexpensive gas Chromatographic method is described that allows simultaneous measurement in urine of androsterone (A), aetiocholanolone (E), 11-hydroxyandrosterone (11-OA), 11-hydroxyaetiocholanolone (11-OE), pregnanediol (PD), pregnanetriol (PT), tetrahydrocortisone (THE) and tetrahydrocortisol (THF). Dehydroepiandrosterone was also resolved by the column. Ibuprofen was administered to five healthy normal males at a dose used therapeutically in rheumatoid arthritis (RA). The above urinary steroids were measured weekly during a control period, during a four week period of drug treatment and for four weeks after drug treatment had ceased. The excretion of A fell to a mean of 63% of the control value ( P < 0.02) and returned to the control value within two weeks. 11-OA, which showed a greater variability than A, fell to the same extent ( P < 0.1). No other steroid measured showed a change that could be related to the drug.

Licorice Raises Urinary Cortisol in Man*

The finding that urine cortisol excretion was increased in patients with hypokalaemic hypertension induced by licorice addiction led to this study on the effect of licorice in normal subjects. Thirteen normal volunteers ate either 100 or 200 g licorice for 1-4 weeks and assessment of pituitary-adrenal function was made before, during, and 1 week after cessation of licorice ingestion. Urine cortisol excretion more than doubled in 10 of 13 subjects (mean, 33.8 +/- 15.6 SD before and 83.3 +/- 56 SD micrograms/24 h at 1 week after commencing licorice) and excretion rates similar to those observed in Cushing's syndrome were seen in 7 subjects (range, 91-226, compared to normal range of 11-82 micrograms/24 h). Urine cortisol excretion remained significantly elevated (P less than 0.01) above control levels for at least 1 week after licorice was withdrawn. Despite these increases, urinary steroid metabolite (tetrahydrocortisol, tetrahydrocortisone, tetrahydro-11-deoxycortisol, 17-ketogenicsteroids, and 17-ketosteroids) excretion was not affected, plasma cortisol and ACTH values were unchanged, and normal 0800-1600-h diurnal variation of plasma cortisol was maintained. The direct intraadrenal infusion of the active mineralocorticoid component of licorice, glycyrrhetinic acid, in two sheep with autotransplanted adrenal glands failed to stimulate cortisol secretion acutely. It is concluded from these studies that the licorice-induced changes in cortisol excretion are not a result of adrenocoritcal stimulation but more likely represent a change in the renal handling of cortisol.

Steroid hormone metabolism in developing rats.

1 The metabolism of [4-14C]pregnenolone in male and female rats 9, 14, 21, 28, 35, 49, 63 and 85 days of age has been studied. Rats 9, 14 and 21 days of age excreted large amounts of monoand disulphurylated [4-14C]pregnenolone metabolites and no sexual differences were seen in the distribution of radioactive metabolites between free steroid, monosulphate and disulphate fractions. At the age of 28 days female rats excreted more steroid sulphates than male rats and in older rats this sexual difference became successively more apparent. 2 The excretion of endogenous steroid metabolites in faeces and urine from male and female rats 28–34, 35–41, 42–48 and 49–55 days of age has been investigated. Sexual differences were found already at an age of 28–34 days; at this time female rats excreted several metabolites identical to those previously described in faeces and urine from adult female rats. Female rats 42–48 and 49–55 days of age had a pattern of steroids identical to that in adult rats. Only small amounts of endogenous steroids were found in male rats; these compounds were not identified. 3 The capacity of adrenals and gonads from rats of various ages to oxidize pregnenolone into progesterone has been studied. The specific 3β-hydroxy-Δ5-steroid-oxidoreductase activity in adrenals from female and male rats as well as in ovaries increased about 5–10 fold from 7 to 56 days of age; the most pronounced increase occurred between 28 and 42 days. There was only a small increase in specific testicular 3β-hydroxy-Δ5-steroid-oxidoreductase activity with age. No significant sexual differences were found in the adrenal 3β-hydroxy-Δ5-steroid-oxidoreductase activity.

Thyroid and steroid hormones and their relation to serum lipid concentrations in man.

Serum levels of cholesterol, phospholipids, total lipids, free fatty acids and protein-bound iodine as well as urinary excretion of steroid metabolites were measured in healthy men and women of 3 age groups prior to and after administration of triiodothyronine. In older men and women, besides an increase in serum lipids, there was also found an elevated urinary etiocholanolone/androsterone ratio. Protein-bound iodine did not change with age, whereas urinary total 17-ketosteroids, but not 17-ketogenic steroids, were lowered. After administration of triiodothyronine the extent of changes of serum cholesterol, phospholipids and total lipids was found to depend on their initial level. No such correlation was found in the case of free fatty acids. Protein-bound iodine levels as well as the urinary etiocholanolone/androsterone ratio were decreased after triiodothyronine in all groups. The possible relation between the elevated etiocholanolone/androsterone ratio and thyroid hormones in old people is discussed. S...

The effects of some steroid hypocholesterolaemic agents on urinary steroid excretion

The urinary excretion of steroid metabolites in hypercholesterolaemic patients prior to and after the administration of dehydroepiandrosterone (3β -hydroxyandrost-5-ene-17-one) and Atromide/androsterone (3α -hydroxy-5α -androstan-17-one) and ethyl-α -p-chlorophenoxyisobutyrate/have been examined. Not only the anticipated rise in C 19-metabolites was found but also a significant rise in the excretion of 17-ketogenic steroids and of some individual C 21-metabolites occured. After cessation of the medication the excretion levels return radiply to normal values. It is suggested that the administred androgens interfere with the metabolism of adrenocortical hormones. There are several possible routes which may explain the mechanism of this action.

Steroid excretion in idlopathic hirsutism.

SUMMARY The excretion of urinary steroids and their response to corticotrophin has been studied in a group of patients with idiopathic hirsutism. The mean resting levels of 17-oxosteroids and 17-hydroxycorticosteroids were higher, and the response to corticotrophin was greater, in the patients as compared to control subjects. Fractionation of 17-oxosteroids in eight patients showed an elevated or abnormally high excretion of steroid metabolites which were presumably being derived from androgen. This appeared to be associated with an adequate production of cortisol, as judged from urinary excretion studies.

Effects of semistarvation and water deprivation on adrenal cortical function and corticosteroid metabolism.

The urinary excretion of 17-KS and 17-OH-CS and the level of circulating unconjugated 17-OH-CS in the plasma were determined in 12 healthy young subjects during a 16-day period of acute undernutrition. In half the group, the intake of water was also significantly restricted during the first 5 1/2 days. The data indicate that although the urinary excretion of steroid metabolites decreased rapidly during the first 6 days of undernutrition and then stabilized at a level approximately half that seen in the control period, the level of circulating unconjugated 17-OH-CS in the plasma was not depressed by this degree of acute undernutrition and protein deprivation. Dehydration increased the level of circulating unconjugated 17-OH-CS, indicating that the pituitary-adrenal axis could respond to ‘stress’ when the diet was calorically inadequate and protein-deficient. These findings have been interpreted as indicating that acute undernutrition and protein deprivation alter the catabolism of adrenal steroids, but that the level of circulating hormonally-active corticosteroids reaching the tissues of the organism is probably adequate. Submitted on July 28, 1958

A comparative study of the disappearance of radioactive sodium from human uterine muscle in normal and abnormal pregnancy

The pioneering work of several British investigators1–4 on placental and myometrial circulation has provided a new approach to the study of normal and abnormal physiology in the human gravid uterus. Their methods consist of injecting a tracer amount of radioactive sodium into the intervillous space and/or the myometrium and recording the time for one half of the radioactivity to disappear. Their experimental results show that there is a delay in the disappearance of radioactive sodium from the injected sites in cases of toxemia as compared to normal controls. They interpret these data to indicate reduced placental and myometrial circulation in the toxemias of pregnancy.With the use of this same tracer technique, preliminary studies5, 6 performed in this department indicated that premature labor was associated with three rather constant factors: reduced urinary excretion of steroid metabolites, increased uterine contractility, and delayed disappearance of radioactive sodium from the myometrium. These changes were observed most frequently in complicated prematurity, but were found also in patients who were delivered prematurely without apparent cause. This study was designed to establish the pattern of disappearance of radioactive sodium from the myometrium during the last half of normal pregnancy and to compare these data with those from abnormal pregnancy, both full term and premature.

Effect of Steroid Administration on Excretion of $aL-Ketolic Steroids and Sulfur in Cats

Summary1. Administration of Δ1-cortisone and 9$aL-fluorohydrocortisone changes normal urinary excretion of steroid metabolites, indicating adrenal depression or altered steroid metabolism. 2. Only a small proportion of administered 9$aL-fluorohydrocortisone is excreted as $aL-ketolic metabolites; Δ1-cortisone also is converted to a great extent to non-$aL-ketolic elements. 3. Elemental sulfur has been found to give a positive reaction with blue tetrazolium. This interferes with the quantitative determination of $aL-ketols in extracts of cat urines. 4. The $aL-ketols and sulfur can be separated by chromatography and each determined quantitatively by the blue tetrazolium reaction, using a modified method. 5. Administration of Δ1E and 9$aL-fluorohydrocortisone causes an increase in urinary excretion of sulfur-containing compounds in cats, which leads us to conclude that these steroids alter sulfur metabolism.