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Biomedical subjects

C R Edwards

Publications and source records attributed to C R Edwards.

At least 181 records · Page 10Linked to original sources
PubMed1982

Testosterone metabolism by the rat gastrointestinal tract, in vitro and in vivo.

We have shown previously that the capacity of the jejunal mucosa to oxidise testosterone to the weaker androgen, androstenedione, by the enzyme 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD), is considerable. The present study extends these earlier observations by measuring 17 beta-HSD activity in different regions of the gastrointestinal tract, by investigating the potential for testosterone metabolism by slices and everted sacs of rat jejunum, and estimating the contribution of intestinal testosterone metabolites to circulating levels of plasma androgens, by portal vein sampling in the rat, in vivo. 17 beta-HSD activity in homogenates of gastric and duodenal mucosa was significantly higher than that in jejunum, and was also present in ileum and colon. In addition to androstenedione, slices and everted sacs of rat jejunum produced various metabolites, one of which was probably dihydrotestosterone. It was not, however, a major metabolite in vivo. It is suggested that 5 alpha-reduction may be favoured in vitro by a lower oxidation-reduction potential resulting from tissue anoxia. The major portal vein metabolite was androstenedione, the same major metabolite produced by mucosal homogenates. We conclude that oxidation of testosterone is the major metabolic pathway in intestinal mucosa and the capacity of the gastrointestinal tract to reduce the potency of testosterone is considerable. Our findings suggest that the gut, rather than the liver, is responsible for the failure of oral testosterone to provide effective androgen replacement therapy. The qualitative difference in testosterone metabolism between in vitro and in vivo preparations emphasises the need for caution in the interpretation of similar in vitro experiments.

17-Hydroxysteroid Dehydrogenases↗
PubMed1982

Progesterone, prolactin, and gynaecomastia in men with liver disease.

Plasma progesterone was raised in 36 of 50 (72%) men with liver disease compared with 20 healthy male control subjects. Plasma progesterone was significantly higher in men with non-alcoholic cirrhosis with gynaecomastia than those without, but no similar relationship was found in men with alcoholic fatty change and alcoholic cirrhosis. Hyperprolactinaemia was found in 14% of men with liver disease but levels were unrelated to the presence of gynaecomastia. Increased circulating levels of progesterone and prolactin alone do not explain the development of gynaecomastia in patients with liver disease, but progesterone may be an additional factor acting in association with the known disturbances of other sex steroids.

Adult↗
PubMed1982

Male gonadal function in coeliac disease: 1. Sexual dysfunction, infertility, and semen quality.

The prevalence of hypogonadism, sexual dysfunction and abnormalities of semen quality was determined in 28 consecutive males with coeliac disease. These observations were related to jejunal morphology and nutritional status, and were compared with findings in 19 men with Crohn's disease of similar age and nutritional status. Two of the 28 coeliacs (7%) had clinical evidence of hypogonadism but impotence and decreased sexual activity occurred more commonly, the latter apparently improving after gluten withdrawal. Of the married coeliacs, 19% had infertile marriages, a value greater than expected in the general population. Hypogonadism and sexual dysfunction were not detected in our patients with Crohn's disease. Seminal analysis in coeliacs revealed marked abnormalities of sperm morphology and motility, but only the former appeared to improve after gluten withdrawal. Similar abnormalities, however, were also detected in patients with Crohn's disease, although, unlike the coeliacs, 46% also had reduced concentrations of spermatozoa. Semen quality in coeliac disease could not be clearly related to general or specific (serum vitamin B(12) and red cell folate) nutritional deficiencies or to fertility, although sperm motility was markedly reduced in two of the three coeliacs with infertile marriages. The presence of antisperm antibodies did not appear to be an important aetiological factor in male infertility in coeliac disease. The pathogenesis of infertility and sexual dysfunction in coeliac disease remains unclear, suggesting that factors such as endocrine dysfunction or other specific nutritional deficiency may be involved.

Adolescent↗
PubMed1981

Development and application of a simple radioimmunoassay for urinary aldosterone.

A simple, economical and direct assay was developed to measure aldosterone in urine, using aldosterone antibody of high specificity and gamma labelled ligand. The assay allows the direct measurement of aldosterone in 100 microliters aliquots of urine after acid hydrolysis. It does not require preliminary solvent extraction and purification steps and hence a large number of samples in a single batch can be assayed simultaneously. An excellent correlation was obtained between the results of the direct assay and the levels measured after extraction and paper chromatography. (Y = 0.97X + 0.89, r = 0.99, p less than 0.001) or after extraction alone (Y = 0.98X + 1.75, r = 0.99, p less than 0.001). The coefficients of variation for inter-assay and intra-assay determinations of samples from normal and high urine pools were 4.2-6.5% and 5.6-9.8%, respectively. Total urinary aldosterone excretion in 21 normal subjects on unrestricted sodium diet ranged from 3.8-20.2 micrograms/24 h (10.5-55.0 nmol/24 h) with a mean of 12.5 +/- 4.6 (SD) micrograms/24 h (34.7 +/- 12.8 (SD) nmol/24h).

Aldosterone↗
PubMed1981

Circulating human pituitary pro-gamma-melanotropin enhances the adrenal response to ACTH.

The amino-terminal region of the common corticotropin/beta-lipotrophin (beta-LPH) precursor has been identified in the AtT-20 mouse tumor cells as a glycopeptide with an apparent molecular weight of 16,000 (the '16K fragment'). A third melanotropin core sequence or gamma-MSH similar to that found in ACTH and beta-LPH was predicted to occur in this glycopeptide from the complementary DNA sequence of mRNA isolated from bovine pituitary intermediate tissue. Recently, the mouse of 16K fragment has been found to have a small but significant potentiation on the corticosteroidogenesis elicited by ACTH in a static cell system, an effect that could be enhanced when the glycopeptide was pretreated with trypsin. This synergism could also be mimicked by synthetic gamma-MSH peptides in vitro and in vivo. We report here the potentiating properties of a naturally occurring human pro-gamma-MSH glycopeptide on the ACTH-induced steroidogenic response of isolated perfused rat and human adrenocortical cells.

Adrenal Cortex↗
PubMed1981

Magnetisable solid-phase separation fluoroimmunoassay for total oestriol in pregnancy serum.

A rapid separation fluoroimmunoassay for serum or plasma levels of total oestriol in pregnancy was established, based on the use of fluorescein-labelled oestriol and sheep anti-oestriol serum covalently linked to magnetisable particles. Equilibrium was attained within 10 min, and the fluorescence of the bound fraction of labelled ligand was quantitated fluorimetrically after elution from the magnetisable particles. Results for pregnancy serum samples correlated well with an established radioimmunoassay technique and the sensitivity, precision and accuracy were appropriate for clinical use. Advantages of this system as compared with radioimmunoassay include the speed and simplicity of end-point detection, prolonged shelf-life of the labelled reactant and absence of any health hazard. The separation step enabled the removal of any endogenous fluorophores or other interfering factors present in biological samples.

Animals↗
PubMed1981

The development and application of a direct radioimmunoassay for corticosterone.

A direct, simple and highly specific radioimmunoassay for corticosterone has been developed. The assay does not require preliminary solvent extraction of the sample or any chromatographic step. The assay utilises a highly specific antibody raised in rabbits against corticosterone-3-(0-carboxymethyl)-oxime-BSA immunogen and gamma-labeled corticosterone of high specific activity. An excellent correlation was obtained between results of the direct assay and those measured after paper chromatography (r = 0.99, P less than 0.001). The coefficients of variation for intra-assay and inter-assay determinations of samples from normal and high plasma pools were 4.6-6.2% and 6.4-8.2% respectively. The minimum limit of detection was 5 pg/assay tube (0.1 ng/ml). The assay has been applied to assess plasma corticosterone levels in various physiopathological and pathophysiological studies. It is extremely practical to the extent that a single technician can assay up to 1000 samples in a working week. Finally, the direct assay has been validated and employed for in vitro adrenal superfusion studies using either rat or human adrenal cells. The large numbers of samples produced by these studies would have exceeded the capacity of earlier radioimmunoassays requiring initial extraction and chromatography.

Adrenal Glands↗
PubMed1981

Evaluation of the mineralocorticoid activity of 18-hydroxycorticosterone.

1. The mineralocorticoid activity of 18-hydroxycorticosterone (18-OH-B) has been compared with that of aldosterone by using human bioassay in vivo with measurement of rectal potential difference and urinary log 10 Na+/K+ ratio. 2. A log-linear relationship was found between maximum change in rectal potential difference and increasing doses of aldosterone. 3. No mineralocorticoid activity could be demonstrated after an intravenous bolus and infusion of 18-OH-B. 4. The half-life of clearance of 18-OH-B was measured in three subjects and found to be 28, 48 and 24 min.

18-Hydroxycorticosterone↗
PubMed1981

Clinical experience with 75Se selenomethylcholesterol adrenal imaging.

The results of quantitative adrenal imaging using 75Se selenomethylcholesterol in sixty-two subjects are analysed. The adrenal area was localized by a renal scan, lateral views of which enabled adrenal depth to be estimated. The first nineteen cases were scanned with a rectilinear scanner and the remaining forty-three cases imaged with a gamma camera. Quantitation of adrenal uptake was performed on computer-stored static images obtained 7 and 14 days post-injection of 75Se selenomethylcholesterol (3 and 6 days in the first ten cases studied). Normal uptake was found to be 0.07-0.30% of the administered dose. Overall predictive accuracy of the type of adrenal disorder of thirty-two patients with Cushing's syndrome ws 90.6%, this included twelve cases of Cushing's disease (mean uptake 0.58%), seven ectopic ACTH syndromes (mean uptake 0.69%), five unilateral adenomata (mean uptake 0.93%), three post adrenalectomy regrowths (mean uptake 1.37%), three adrenal carcinomas (mean uptake 0.01%), one congenital hyperplasia (mean uptake 3.4%) and one unilateral nodular hyperplasia. Overall predictive accuracy of the cause of Conn's syndrome in twenty-two cases was 86.4%; this included thirteen cases of bilateral hyperplasia (mean uptake 0.34%), eight unilateral adenomata (mean uptake 0.47%) and one patient with mineralocorticoid excess in whom the cause has not been confirmed. The mean uptake in the normal adrenal in cases of unilateral adenoma was 0.19% (range 0.07-0.30%). Causes of unsatisfactory adrenal imaging are examined. The procedure is recommended as the localizing and lateralizing technique of choice in Cushing's syndrome except where due to adrenal carcinoma, and as an important non-invasive technique in Conn's syndrome for the lateralization of adenoma.

Adrenal Glands↗
PubMed1981

Nocturnal growth hormone and gonadotrophin secretion in growth retarded children with Crohn's disease.

Although impaired growth hormone secretion in response to pharmacological stimuli occurs in some growth retarded children with Crohn's disease, its relationship to past and future th is uncertain. We have therefore determined the growth hormone and gonadotrophin response to the physiological stimulus of sleep by continuous venous sampling in five severely gonadotrophin profiles, the mean plasma hormone concentrations during the first five hours of sleep were determined. In three of the five patients, five hour mean growth hormone levels were reduced (3.8, 5.0, and 8.5 mU/l) compared with levels reported previously in normal short children (10-43 mU/l), although the pulsatile pattern of growth hormone secretion was preserved in all. Nocturnal growth hormone secretion was unrelated to the growth velocities of these children during both pre- and post-treatment assessment periods but a significant correlation was found between growth hormone concentration and a disease activity score (r = 0.79, P less than 0.05), suggesting that growth hormone release by the pituitary was influenced by the severity of the disease. Nocturnal growth hormone secretion was also correlated with gonadotrophin secretion (luteinising hormones, r = 0.99, and follicle stimulating hormone, r = 0.96; p less than 0.01) indicating more extensive hypothalamic-pituitary disturbance. These findings suggest that hypothalamic-pituitary function is depressed in growth retarded children with Crohn's disease, but that abnormalities of growth hormone secretion are unlikely to be directly involved in the growth retardation seen in this condition.

Adolescent↗
PubMed1981

Effects of two different angiotensin II antagonists on aldosterone secretion by isolated perfused rat zona glomerulosa cells.

Isolated perfused rat zona glomerulosa cells have been used to determine the specificity of the angiotensin II antagonists, [Sar1,Ala8]angiotensin II and [Sar1,Ile8]angiotensin II. Both antagonists inhibited the aldosterone response to angiotensin II but did not affect serotonin- or potassium-induced aldosterone secretion. However, in contrast to [Sar1,Ala8]angiotensin II, [Sar1,Ile8]angiotensin II inhibited the aldosterone response to ACTH. These results suggest that there are differences in the specificity of these two analogs and that studies with [Sar1,Ile8]angiotensin II and its effect on aldosterone secretion should be interpreted with caution.

1-Sarcosine-8-Isoleucine Angiotensin II↗
PubMed1981

In vitro studies on the effects of ranitidine on isolated anterior pituitary and adrenal cells.

The effects of ranitidine on anterior pituitary and adrenal function have been studied using isolated perfused rat anterior pituitary and zona glomerulosa cells. Ranitidine did not have pituitary hormone releasing activity with respect to LH, TSH, GH and ACTH. It also did not alter prolactin secretion in experiments designed to test whether it acted as a dopamine agonist or antagonist. In the adrenal cell studies ranitidine infusion stimulated basal aldosterone secretion and inhibited the release of aldosterone in response to angiotensin II, but not to ACTH. These experiments suggest that ranitidine is unlikely to alter pituitary hormone secretion by a direct action on the pituitary. The drug, however, can affect aldosterone secretion in vitro and further in vivo studies are required to elucidate the significance of this.

Adrenal Cortex↗