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PubMed1982

Serotonin metabolism and depression in oral contraceptive users.

Serotonin and nicotinic acid ribonucleotide metabolic pathways of tryptophan metabolism were studied before and after tryptophan load test in thirty women using oral contraceptive steroids for a period of 2 to 5 years. Ten of them were suffering from depression. Another ten healthy women participated in this study as a control group. Twenty-four-hour urinary excretion of serotonin, 5-hydroxyindole acetic acid and total 5-hydroxyindoles were estimated as indices of serotonin pathway metabolites, while xanthrenate excretion was determined as an index of tryptophan oxygenase pathway. Plasma cortisol, urinary 17-oxosteroids and 17-hydroxycorticosteroids were determined to assess adrenal cortical function. Urinary creatinine output was assayed to check the adequacy of 24-hr urine collection. The changes induced by oral contraceptive steroids on tryptophan and corticosteroid metabolism were correlated with the associated depression. Changes in serotonin metabolism were demonstrated in the depression group before and after tryptophan load test, while in the non-depression group before and after tryptophan load test, while in the non-depression group, these changes were only demonstrated after tryptophan load test. Results indicated the alteration in tryptophan metabolism are usually well compensated in the non-depression group but may accentuate or precipitate the development of depression in susceptible women.

Adult↗
PubMed1985

In vitro steroid biosynthesis by the adrenal gland of the female Lacerta vivipara Jacquin: the metabolism of exogenous precursors.

The synthesis of steroids in vitro by adrenal glands from female Lacerta vivipara J., using various labeled steroids as substrates, was studied. Effects of two enzymatic inhibitors (cyanoketone and elipten) on steroid synthesis was analyzed. As in other reptilian species, no 17-hydroxycorticosteroids were detected and the major biosynthetic pathway operating in vitro proved to be that of 17-deoxycorticosteroids. An important synthesis of an unidentified compound (X) was observed only from pregnenolone. Incubations of L. vivipara adrenal glands have been performed using [3H]pregnenolone plus [14C]progesterone at different phases of the annual cycle. Changes in adrenal steroid activity, related to season and physiological state of female, are quantitative rather than qualitative. High production in vitro of progesterone and 18-hydroxycorticosterone is associated with gestation whereas high production of deoxycorticosterone and corticosterone is observed during hibernation.

Adrenal Glands↗
PubMed1984

The stimulation by ACTH of 17 alpha-hydroxylation in cultures or rabbit adrenal cells.

Adrenal cells from control rabbits (control-cells) and from rabbits that had been injected twice daily for 3 days prior to sacrifice with 25 IU ACTH (ACTH-cells) were cultured both in the absence and presence of 100 mIU ACTH. Culture durations varied from 24 to 120 h in 24 h increments. The culture medium was changed daily and fresh ACTH added to appropriate vessels. At the time of the final media change 0.1 muCi [4-14C]pregnenolone was added. Twenty-four hours later the cultures were terminated and the products formed from the pregnenolone were isolated, quantified and identified by solvent extraction, chromatography and crystallization to constant specific activity. After 72 h ACTH-cells cultured in the presence of ACTH converted 18.5% of the pregnenolone substrate to 17-hydroxycorticosteroids (cortisol plus 11-deoxycortisol) while ACTH-cells cultured in the absence of ACTH converted a maximum of 1.6%. A similar but smaller difference, 10.9 vs 2.1%, was recorded with control cells cultured in the presence and absence of ACTH. Corticosterone production from [4-14C]pregnenolone in the 72-h cultures was increased to a lesser degree by ACTH exposure. In ACTH-cells the conversion climbed from 5.9 to 10.5% and from 9.6 to 12.0% in control cells. Microscopic examination of parallel cultures showed no significant differences in cell density between cells cultured in the presence or absence of ACTH. 17 alpha-Hydroxylase activity arising from the in vivo stimulation did not survive cell division in culture, but required the continual presence of ACTH. In conclusion, the data show that ACTH is capable of stimulating 17-hydroxycorticoid formation in rabbit adrenal cell cultures.

Adrenal Glands↗
PubMed1989

Corticosteroid sulfates in fetus plasma.

The sulfates of deoxycorticosterone (DOCS), corticosterone (BS), cortisone (ES) and cortisol (FS) were radioimmunoassayed in umbilical vein blood plasma samples collected in 97 fetuses between 19 and 32 weeks of gestation after extraction and chromatography on Sephadex LH 20 columns. While DOCS and BS displayed a decreasing pattern until 27-28 weeks, FS and ES did not show important variations throughout the period considered. All sulfates, excepted BS, increased at 29-30 weeks but this rise was only significant for FS and ES. Thereafter BS significantly increased while no significant difference could be displayed for the three others. In view of the difference between the patterns of 17-deoxy- and 17-hydroxycorticosteroids, one can speculate that, during this period of pregnancy, a shift in steroid biogenesis might occur towards a more important production of cortisol. DOCS was correlated with BS and with FS but not with ES. FS was correlated with the three other sulfates and with unconjugated F. ES was correlated with BS and FS but not with DOCS or unconjugated E. The significance of these correlations are discussed according to the origin and the metabolic interrelationships of the four steroid sulfates and unconjugated F and E.

Adrenal Cortex Hormones↗
PubMed1975

Clinical testing of the hypothalamic-pituitary-adrenocortical system in states of hypo- and hypercortisolism.

Cortisol production is appropriately maintained by a complex control system which involves primarily the hypothalamus, the pituitary, and the adrenal cortices. Very small quantities of ACTH stimulate cortisol production, and maximum stimulation occurs with serum concentrations of only 3 mU/100 ML. Under normal circumstances, cortisol is secreted in bursts about ten times each day and circulates predominately bound to a specific binding protein which is rather completely saturated. Radioimmunoassay of plasma cortisol is now generally available and is the assay method of choice, but because of the episodic nature of its secretion, random values of plasma cortisol must be interpreted with great reservation, and even the comparison of morning and evening values in assessing circadian rhythmicity is not often helpful. Urinary free cortisol determinations provide excellent discrimination between normal function and all forms of hypercortisolism. Although the response of the adrenal cortices to ACTH may be evaluated in a number of different ways, the simplest but most definitive procedure involves continuous intravenous administration over a 48-hr period. Of the various tests which indirectly assess the potential for ACTH secretion, the use of metyrapone is most helpful. In the test of greatest utility, plasma cortisol and 11-desoxycortisol are determined the morning after a single midnight oral dose of 30 mg/kg. The detection of all forms of pathologic hypercortisolism is still best accomplished by the oral administration of dexamethasone. Plasma cortisol can be determined the morning after a single midnight dose of 1 mg, or urinary 17-hydroxycorticosteroids can be determined after 2 days in which 0.5 mg is given at 6-hr intervals. Patients with hypercortisolism of hypothalamic-pituitary origin usually evidence appropriate suppression of urinary steroids if the dose is increased to 2.0 mg every 6 hr for another 48 hr. In patients who do not suppress on this or even higher doses of dexamethasone, the distinction between those with adrenal tumor and those with the ectopic ACTH syndrome can be accomplished most definitively by the assay of plasma ACTH where this determination is available.

Adrenal Cortex↗
PubMed1979

Cushing's syndrome: a review of diagnostic tests.

This review presents an analysis and interpretation of the published experimental data that form the basis for laboratory tests commonly used for screening, definitive diagnosis, and differential diagnosis in Cushing's syndrome. The single-dose overnight dexamethasone suppression test is excellent for screening outpatients since this test has a very low incidence of false-negative results (1.9% of 154 patients with Cushing's syndrome). The definitive diagnosis of Cushing's syndrome is best established by combining basal state measurements of the daily urine-free cortisol excretion and late evening plasma cortisol levels with the 2-mg low-dose dexamethasone suppression test. The etiology of Cushing's syndrome is best determined by combining measurements of basal state plasma adrenocorticotropin (ACTH) levels with the 8-mg high-dose dexamethasone suppression test. Under certain conditions, the basal state daily urine excretion of 17-hydroxycorticosteroids and 17-ketogenic steroids, the insulin tolerance test, and the metyrapone test may be useful in the definitive or differential diagnosis of Cushing's syndrome.

Adrenal Cortex Hormones↗
PubMed1985

Endocrine and protein response to elective surgery: effect of nursing at two different environmental temperatures.

Twenty male patients undergoing elective abdominal surgery were studied on one control day pre-operatively and for the first 4 days postoperatively at an environmental temperature of either 20 degrees C or 28 degrees C. Glucose, insulin, growth hormone and urinary catecholamine levels all rose significantly on the first postoperative day returning to within normal limits by day 4. Urine nitrogen excretion also increased significantly postoperatively in both groups. Environmental temperature did not influence these responses. Concentrations of C-reactive protein and a1-antichymotrypsin increased significantly on the first postoperative day and were returning to normal by day 4 while concentrations of haptoglobin, a1-antitrypsin and a1-acid glycoprotein, which also showed a significant increase, remained elevated at the end of the study. Concentrations of albumin, transferrin, a2-macroglobulin, prealbumin and retinol binding protein all decreased significantly following operation. Elevated environmental temperature did not affect the protein response to surgery. Urine cortisol and 17-hydroxycorticosteroid excretion rose significantly postoperatively and remained elevated throughout the study. Patients nursed at 28 degrees C showed significantly lower postoperative excretion of both hormones than patients nursed at 20 degrees C.

Journal Article↗
PubMed1995

Endocrine and psychological evaluation of women with recent weight gain.

A group of 13 consecutive regularly menstruating women who gained at least 5 kg the previous year (Group I) was compared to a control group of similar age, parity, and social class (Group II). The two groups were similar in estimated and observed food intakes; pre- and postprandial gastrin levels; hourly 24-h profiles of cortisol and insulin; urinary cortisol and 17-hydroxycorticosteroids. Group I had higher serum prolactin concentrations at all times than Group II (mean values 14.60 micrograms/l vs. 8.84 micrograms/l; p = .0121). Galactorrhea was observed in 5 women from Group I and in none of the women from Group II (p < .05). Group I also differed from Group II in a higher incidence of meaningful life-events the year preceding the study, higher prevalence of sexual dysfunction (9/13 vs. 4/13; p < .01) and higher indexes (p < .05) of several parameters in the MMPI and SCL 90. Median serum cortisol and prolactin concentrations were negatively correlated, both in Group I (R = -.669; p = .012) and in the whole sample (R = -.453; p = .0298). It is suggested that the rapid weight gain is part of a neuroendocrine response to environmental stimuli also characterized by hyperprolactinemia. The significant negative correlation between serum prolactin and cortisol indicates that this response differs from, and is possibly an alternative to, the sympathoadrenal "stress" response.

Adult↗
PubMed1987

Application of high-performance liquid chromatography to the measurement of cortisol secretion rate.

After administration of [3H] cortisol, the specific radioactivity of the urinary cortisol metabolites is determined by chemical conversion of the 17-hydroxycorticosteroid conjugates to 17-ketosteroids, extraction with Sep-Pak C18 cartridges, derivatisation with 2,4-dinitrophenylhydrazine and isocratic reversed-phase high-performance liquid chromatography. This allows on-line measurement of ultra-violet absorbance; fractions are collected and 3H is measured by scintillation counting. Alternatively extraction and chromatography are done after enzymic hydrolysis of the steroid conjugates, and the major metabolites are determined colorimetrically in the fractions. The results from the two methods were consistent with each other and with published data.

Adult↗
PubMed1993

Biochemical effects of Catha edulis, cathine and cathinone on adrenocortical functions.

Catha edulis is a plant that grows in certain areas of East Africa and the Arab Peninsula. The stimulating properties of fresh material were described more than seven centuries ago and today the habit of inducing a state of euphoria and subjective well-being by chewing Catha edulis prevails among the inhabitants of these regions. Oral administration of this plant and its active constituents (cathine and cathione) on experimental animals might have stimulating effects on adrenocortical function. This was indicated by the significant decrease in adrenal cholesterol, ascorbic acid, glycogen, and the increase in adrenal phosphorylase activity. In addition, the level of urinary 17-hydroxycorticosteroids and plasma free fatty acids were increased.

Adrenal Cortex↗
PubMed1995

Disparate circadian variations of blood pressure and body temperature in bedridden elderly patients with cerebral atrophy.

Twenty bedridden elderly patients with normal sleep-wake cycles were studied to evaluate the circadian variations of blood pressure, pulse rate, body core temperature, cortisol, and catecholamines with a focus on their relation to cerebral atrophy. Twenty-four-hour blood pressure (BP) and pulse rate monitorings were done with simultaneous measurement of urinary bladder temperature. Urine was also collected every 4 h to measure 17-hydroxycorticosterone and catecholamines. Based on the brain CT, frontal horn index (FHI: maximal distance between bilateral frontal horns/the corresponding width of the skull) was calculated as an index of cerebral atrophy. Analysis by the cosinor method revealed that the significant circadian rhythm with nocturnal decline was observed in only 9 patients (45%) for BP and in 13 patients (65%) for pulse rate. In contrast, 19 of 20 patients (95%) showed significant circadian rhythms of bladder temperature, with the nadirs appearing between 00:06 and 06:54. In the subgroup of mild cerebral atrophy (FHI < 0.30, n = 11), BP and pulse rate fell modestly but significantly during nighttime, whereas they did not fall in the subgroup of moderate to severe cerebral atrophy (FHI > or = 0.30, n = 9). The possibility could not be excluded that the sleep disturbance might result in the relatively high BP during nighttime. Bladder temperature, 17-hydroxycorticosteroids, and catecholamines showed significant nocturnal falls in both groups. In conclusion, nocturnal fall of BP disappeared in the bedridden elderly patients with cerebral atrophy, which cannot be explained by the change in the circadian variation of the sympathetic nervous system, cortisol, or body core temperature.

Aged↗
PubMed1975

Acomparative study of two methods of urine preservation.

In preparation for the conduct of biochemical experiments in the Skylab Orbital Workshop a study was performed on the stability of various chemical constituents in urine in 2 different techniques for preservation and storage. Urine samples were either vacuum dried or frozen and maintained in storage at minus 20 degrees for periods of up to 10 weeks. The urinary constituents studied included aldosterone, antidiuretic hormone, epinephrine, norepinephrine, urea, nitrogen, creatine, hydroxyproline, 17-hydroxycorticosteroids, calcium, sodium potassium, chloride, magnesium and phosphate. Some degradation of urinary compounds was observed after both treatments. The rate and variability of destruction following the vacuum drying treatment, however, was greater than for freezing. It was concluded that only the freezing treatment could be used to preserve with predictable loss the urinary samples which would be returned to earth following the conclusion of each Skylab flight.

Aldosterone↗
PubMed2001

TNF-alpha enhances intracellular glucocorticoid availability.

For understanding the mechanism(s) relating inflammation to corticosteroid action, the effect of tumour necrosis factor-alpha (TNF-alpha) on 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2), the enzyme regulating access of 11beta-hydroxycorticosteroids to receptors, was studied in LLC-PK(1) cells. We observed (i) NAD-dependent enzyme activity and mRNA for 11beta-HSD2, but not 11beta-HSD1, (ii) increasing 11beta-HSD2 activity with increasing degree of differentiation and (iii) a concentration-dependent down-regulation by TNF-alpha, phorbol myristate acetate (PMA) or glucose of activity and mRNA of 11beta-HSD2. The decrease of activity and mRNA by glucose and PMA, but not that by TNF-alpha, was abrogated by the protein kinase C inhibitor GF-109203X. The effect of TNF-alpha on 11beta-HSD2 was reversed by inhibiting the mitogen-activated protein kinases ERK with PD-098050 and p38 by SB-202190, or by activating protein kinase A with forskolin. Overexpression of MEK1, an ERK activator, down-regulated the 11beta-HSD2 activity. In conclusion, TNF-alpha decreases 11beta-HSD2 activity and thereby enhances glucocorticoid access to glucocorticoid receptors to modulate the inflammatory response.

11-beta-Hydroxysteroid Dehydrogenase Type 2↗
PubMed1998

Down-regulation of hepatic and renal 11 beta-hydroxysteroid dehydrogenase in rats with liver cirrhosis.

BACKGROUND & AIMS: 11 beta-Hydroxysteroid dehydrogenase (11 beta-OHSD) enzymes are responsible for the interconversion of active 11 beta-hydroxycorticosteroids into inactive 11-ketoglucocorticosteroids and by that mechanism regulate the intracellular access of the steroids to the cognate receptor. A down-regulation of the shuttle of active to inactive glucocorticoids enhances access of glucocorticosteroids to both the glucocorticoid and the mineralocorticoid receptors. In liver cirrhosis, enhanced mineralocorticoid and glucocorticoid effects are observed. We therefore investigated the impact of liver cirrhosis after bile duct ligation on the transcription and activity of 11 beta-OHSD1 and 11 beta-OHSD2 in the corresponding tissues. METHODS: Messenger RNA from 11 beta-OHSD1 and 11 beta-OHSD2 was assessed by reverse-transcription polymerase chain reaction; activity was assessed by measuring the interconversion of corticosterone to dehydrocorticosterone. The effect of bile and bile salts was determined using COS-1 cells transfected with 11 beta-OHSD1 or 11 beta-OHSD2. RESULTS: In liver tissue, the messenger RNA ratios of 11 beta-OHSD1 to glyceraldehyde-3-phosphate dehydrogenase (GAPDH) levels and, in kidney tissue, the ratios of 11 beta-OHSD2 to GAPDH levels decreased after induction of liver cirrhosis. The 11 beta-OHSD activities were correspondingly reduced. Bile and individual bile salts inhibited 11 beta-OHSD1 and 11 beta-OHSD2 oxidative activity in transfected COS-1 cells. CONCLUSIONS: These findings indicate that in liver cirrhosis the mineralocorticoid and glucocorticoid receptor-protecting effects by the 11 beta-OHSD isoenzymes are down-regulated and that by the same mechanism the glucocorticoid and mineralocorticoid effects are enhanced.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1992

The value of adrenal autotransplantation with attached blood vessels for the treatment of Cushing's disease: a preliminary report.

We treated 5 patients with Cushing's disease by total adrenalectomy and left adrenal autotransplantation with attached blood vessels. An end-to-end vascular anastomosis was made between the adrenal central vein and the inferior epigastric artery, and the saphenous vein and adrenal middle artery were anastomosed by intussuscepting the artery into the vein in 4 patients. Steroid replacement was withdrawn 7 to 90 days after bilateral total adrenalectomy. The patients were followed for 1 to 4 years. Repeated measurement of plasma cortisol, 24-hour urinary 17-hydroxycorticosteroid and 17-ketosteroid levels in all cases was normal. As soon as the adrenal central vein and inferior epigastric artery were anastomosed part of the adrenal gland was then excised. Oozing of blood from the cut surface was retained and the adrenal gland was then embedded into the inguinal muscle in 1 patient. Small doses of steroid replacement (12.5 mg. cortisone per day) were still necessary 1 year postoperatively. The result thus indicates that this procedure is feasible and valuable for the treatment of patients with Cushing's disease and no evidence of pituitary adenoma on magnetic resonance imaging or computerized tomography.

Adrenal Glands↗
PubMed1989

Adrenal autotransplantation with attached blood vessels for treatment of Cushing's disease.

A case of Cushing's disease was treated successfully by staged total adrenalectomy, left adrenal autotransplantation with the attached blood vessels and pituitary irradiation. In the first stage the left adrenal gland was removed with its attached blood vessels intact, and adrenal autotransplantation then was performed. An end-to-end anastomosis was made between the adrenal central vein and the right inferior epigastric artery. The anastomosis between the right saphenous vein and the adrenal middle artery was accomplished by intussuscepting the artery into the vein followed by suturing. The second stage operation was total right adrenalectomy. Steroid replacement therapy was stopped 7 days postoperatively and all laboratory studies were normal. Two months after total right adrenalectomy the patient had a sensation of facial fullness. Plasma cortisol and 24-hour urinary 17-hydroxycorticosteroid levels were elevated. Part of the graft was excised with the patient under local anesthesia. The symptoms disappeared and the laboratory studies returned to normal. Pituitary irradiation was administered as supplementary treatment of Cushing's disease. This method for the treatment of Cushing's disease has proved feasible. The inguinal region is the optimal site for adrenal autotransplantation.

Adrenal Glands↗
PubMed1995

Endocrinological and clinical evaluation of exemestane, a new steroidal aromatase inhibitor.

The androstenedione derivative, exemestane (FCE 24304), is a new orally active irreversible aromatase inhibitor. Fifty-six post-menopausal advanced breast cancer patients entered this study to evaluate the activity of four low exemestane doses in reducing oestrogen levels. The drug's tolerability and clinical efficacy were also assessed. Exemestane was orally administered to four consecutive groups at daily doses of 25, 12.5, 5 and 2.5 mg, and the changes in oestrogen, gonadotrophins, sex-hormone binding globulin and dehydroepiandrosterone sulphate levels were evaluated. Drug selectivity was studied by measuring 17-hydroxycorticosteroid urinary levels. After 7 days of treatment, mean oestrone and oestradiol levels had decreased by respectively 64% and 65% (a decrease which was maintained over time); in the 2.5 mg group, oestrone sulphate levels also decreased by 74%. Gonadotrophin levels were significantly higher, whereas no changes in the other serum hormone levels or any interference with adrenal synthesis were detected. Treatment tolerability was satisfactory: nausea and dyspepsia were reported in 16% of patients. The overall objective response rate was 18%. In conclusion, exemestane is effective in reducing oestrogen levels at all of the tested doses and shows interesting clinical activity.

Adult↗
PubMed1993

A crossover comparison of progression of chronic renal failure: ketoacids versus amino acids.

Rates of progression of chronic renal failure were compared in patients receiving alternately an amino acid supplement (AA) and a ketoacid supplement (KA) to a very low protein (0.3 g/kg), low phosphorus (7 to 9 mg/kg) diet. The first supplement was randomly chosen. Bias due to carryover effects was minimized by delaying the regression analysis until one month after starting or changing supplements. In order to minimize possible bias caused by initiating the two supplements at differing levels of severity, a multiple crossover design was used (ABA, BAB, ABAB, or BABA) with at least four GFR's in each treatment period (except for three GFR's in one instance). Sixteen patients completed the protocol; five dropped out. Average starting GFR's were nearly identical for the two supplements (15.4 and 15.9 ml/min). For each patient, mean progression on KA was compared with mean progression on AA. Thirteen out of 16 patients progressed more slowly on KA than AA. On the average, progression on KA was significantly slower (95% confidence limits = -0.36 to 0.09 ml/min/month) than on AA (-0.91 to -0.41 ml/min/month; P = 0.024). There was no significant difference in estimated protein intake, phosphate excretion, or mean arterial pressure between KA and AA periods. Serum triglyceride concentration was significantly lower on KA (P = 0.0026). 17-hydroxycorticosteroid excretion was also lower (P = 0.031). We conclude that KA slow progression, relative to AA, independently of protein or phosphorus intake, in patients on this regimen.

Adult↗