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Biomedical subjects

V H James

Publications and source records attributed to V H James.

At least 73 records · Page 4Linked to original sources
PubMed1986

The relation between aldosterone concentrations in plasma and saliva during pregnancy.

The concentrations of aldosterone and glucocorticoids (cortisol + cortisone) were measured in saliva and plasma samples obtained from healthy women during early (11-19 weeks), mid (24-29 weeks) and late (32-37 weeks) pregnancy. There was a progressive increase in mean aldosterone levels in both saliva and plasma throughout pregnancy, though at each stage of pregnancy the range was very wide. Glucocorticoid levels increased up to mid-pregnancy and then remained constant. At no stage were aldosterone and glucocorticoid levels significantly correlated. The proportion of free (non-protein bound) aldosterone in plasma, and the saliva:plasma ratio of aldosterone did not differ from the non-pregnant range at any stage of pregnancy. We conclude that measurement of aldosterone concentration in saliva is a convenient and valid method for the estimation of plasma free aldosterone in pregnancy and so provide a non-invasive technique for assessing aldosterone status throughout pregnancy.

Aldosterone↗
PubMed1986

Saliva aldosterone concentration in healthy infants.

Aldosterone and glucocorticoid (cortisol + cortisone) concentrations were measured in 106 saliva samples from healthy infants. Most aldosterone values fell within the adult range (0-0.15 nmol/l (0-5.4 micrograms/100 ml)), but 10 were greater than 0.2 nmol/l (7.2 micrograms/100 ml). Aldosterone concentration was not related to sex, ethnic origin, time of collection, distress, or cortisol concentration but decreased with age.

Adult↗
PubMed1985

The relationship between 17 beta hydroxysteroid dehydrogenase and breast tumour site and size.

The activity of 17 beta hydroxysteroid dehydrogenase (170HSD) was measured in adipose tissue adjacent to benign or malignant breast tumours. 170HSD activity was significantly correlated with tumour size in malignant tumours (r = 0.75) but not with benign tumours (r = 0.28). Enzyme activity was reduced in adipose tissue adjacent to tumours obtained from inferior breast quadrants.

17-Hydroxysteroid Dehydrogenases↗
PubMed1985

The distribution of oestradiol in plasma from postmenopausal women with or without breast cancer: relationships with metabolic clearance rates of oestradiol.

The distribution of oestradiol in plasma from postmenopausal women with or without breast cancer has been measured and related to the metabolic clearance rates of oestradiol (MCR-E2). All measurements were carried out preoperatively. No difference in the free fraction of oestradiol was found between women with breast cancer (1.8 +/- 0.4%, mean +/- SD) and normal women (1.6 +/- 0.3%). Approximately 40% of oestradiol in plasma was bound to albumin with 60% bound to sex hormone binding globulin (SHBG), but values were similar for women with or without breast cancer. Concentrations of total unconjugated oestradiol and free oestradiol (2.4 +/- 0.5 ng/100 ml and 44 +/- 12 pg/100 ml respectively, mean +/- SD, n = 9) were significantly higher in plasma from postmenopausal women with breast cancer compared with levels in plasma from normal postmenopausal women (1.8 +/- 0.5 ng/100 ml and 27 +/- 10 pg/100 ml, n = 8). A significant correlation was found between the free oestradiol fraction and MCR-E2 (r = 0.53, p less than 0.05). Correlations were also found between the fractions of oestradiol bound to albumin and MCR-E2 (r = 0.45). From correlations between the binding capacity of SHBG and MCR-E2 it appears that, for a given level of SHBG, MCR-E2 may be higher in women with breast cancer.

Body Weight↗
PubMed1985

Kinetic studies of oestradiol 17 beta-hydroxysteroid dehydrogenase in MCF-7 mammary cancer cells.

The kinetic properties of oestradiol 17 beta-dehydrogenase have been studied in the MCF-7 human breast cancer cell line. The activity of the enzyme was found to be linear with respect to time for at least 2 h and with respect to protein concentrations over the range 40-300 micrograms protein per tube. The enzyme was able to utilize both NAD and NADP as cofactors but at higher concentrations NAD was the more effective. The apparent Km was estimated to be 13.4 microM which is approximately two-fold higher than found for breast tumour tissue.

17-Hydroxysteroid Dehydrogenases↗
PubMed1985

The identification, quantification and possible origin of non-polar conjugates in human plasma.

The existence and quantification of non-polar conjugates of pregnenolone, dehydroepiandrosterone (DHA) and androstenediol in human plasma is described. The plasma level of non-polar pregnenolone conjugate is 200% higher than that of pregnenolone but the conjugates of DHA and androstenediol are 10 and 5-10% respectively of the plasma levels of the unconjugated steroid. Non-polar pregnenolone conjugate concentrations were found to be highly elevated in the plasma of one pregnant subject, and elevated in the plasma of patients with acne and breast cancer. Non-polar DHA conjugate levels were significantly elevated in hirsute patients and were approaching significance for patients with acne. A subject taking the combined oral contraceptive pill had very low plasma DHA conjugate levels. No significant alterations in the plasma levels of the androstenediol conjugates were found. A role for the non-polar conjugates in the aetiology of hirsutism and acne is proposed.

Acne Vulgaris↗
PubMed1985

17 beta-hydroxysteroid dehydrogenase activity in leiomyoma and myometrium and its relationship to concentrations of oestrone, oestradiol and progesterone throughout the menstrual cycle.

The activity of the enzyme 17 beta-hydroxysteroid dehydrogenase (17 beta-OHSD) and concentrations of oestrone (E1), oestradiol (E2) and progesterone have been measured in leiomyoma and myometrium obtained at different stages of the menstrual cycle. Apart from conversion of E2 to E1 in the proliferative phase, no significant difference in enzyme activity was noted between normal and tumour tissue. However, interconversion in both tissues was shown to be higher in the secretory than the proliferative phase of the menstrual cycle. E1 concentrations were significantly higher (P less than 0.01) in leiomyoma than in myometrium, obtained during the proliferative phase. Concentrations of both oestrogens, in some tumour and normal tissues, were higher in the proliferative than the secretory phase. Secretory phase tissues contained higher concentrations of progesterone than those obtained in the proliferative phase of the menstrual cycle. Considerable differences in both enzyme activity and steroid concentrations were noted in different areas of the same tumour.

17-Hydroxysteroid Dehydrogenases↗
PubMed1985

Metabolism of adrenal androgens by human endometrium and adrenal cortex.

The enzyme 17 beta-hydroxysteroid dehydrogenase (17OHSD) was studied in human endometrium and adrenal cortex with respect to the metabolism of 5-androstene-3 beta,17 beta-diol (androstenediol) and dehydroepiandrosterone (DHA). The aim was to provide further information concerning the origin and biological significance of these androgens in endometrium, particularly the increased concentrations of the secretory phase and to compare the characteristics of the enzyme in the two tissues. In both endometrium and adrenal cortex the metabolism of androstenediol to DHA was linear with time and increasing enzyme concentration. The preferred cofactor was NAD and the apparent Km values were 3.4 +/- 0.2 (SD) microM (n = 3) for endometrium and 30.5 +/- 6.1 microM (n = 3) for adrenal cortex. In endometrium DHA was not metabolised to androstenediol in the presence of either NADH or NADPH whereas in the adrenal cortex both cofactors were utilised. However, the concentration of NADH required to achieve maximum enzyme activity was 10-fold higher (1 mM) than for NADPH (0.1 mM) and maximum activity with NADH was only 30% of that using NADPH. The apparent Km was 125 microM DHA (n = 2). The study indicates that androstenediol in endometrium does not arise from DHA metabolism but that its presence could be due to a binding protein particularly during the secretory phase. Our findings also suggest that the enzyme of endometrium differs from that of the adrenal cortex and that the kinetic properties may be related to the physiological requirements of the two tissues.

17-Hydroxysteroid Dehydrogenases↗
PubMed1985

Adrenocorticosteroids: chemistry, synthesis and disturbances in disease.

The biosynthesis of adrenocortical steroids is now a reasonably well understood process, which proceeds by discrete, enzyme directed steps from cholesterol to the various hormonal steroids. However, much of our knowledge derives from studies of animal tissues and there is a need for further studies of human glands. In particular, the details of individual enzyme systems, and the extent and significance of compartmentalization of steroid intermediates requires further exploration. The adrenal metabolic errors also merit further study, to clarify some aspects of congenital adrenal hyperplasia and to explain the relationship between biochemical and clinical observations. The advent of immunoassay methods for the measurement of steroid hormone levels in plasma has changed the approach to diagnostic steroid endocrinology, with less emphasis now on the measurement of urinary steroid metabolites, particularly in regard to androgens. The newer and sensitive methods available also allow the assay of steroid hormones in saliva, and the ready availability of this fluid, and the fact that sampling is a non-invasive technique makes salivary steroid assay an attractive alternative to other, traditional methods of investigation requiring blood or urine collection. Inhibitors of steroid biosynthesis and of steroid action have been used with considerable success in diagnostic techniques and to a limited extent in the treatment of steroid disorders. As our understanding of the details of steroid biosynthesis, mechanism of steroid action, and control of steroid secretion improve, further progress in designing clinically useful inhibitors should be possible.

3-Hydroxysteroid Dehydrogenases↗
PubMed1985

Conversion of estrone to estradiol and estradiol to estrone in postmenopausal women.

The conversion of estrone to estradiol and metabolism of estradiol to estrone have been measured in postmenopausal women to examine factors that influence these conversions. Transfer constants for the conversion of estrone to estradiol and estradiol to estrone were not significantly correlated with age (r = -.01 and r = .1, respectively) or subjects' percentage of ideal body weight (r = -.25 and r = -.22, respectively). There was a significant negative correlation between the transfer constants for the conversion of estradiol to estrone and plasma levels of dehydroepiandrosterone sulphate (r = -.45, P less than .05) but not plasma levels of progesterone. Transfer constants for the conversion of estrone to estradiol and metabolism of estradiol to estrone in women with breast or endometrial disease were similar to values in normal women, but metabolism of estradiol to estrone was elevated in two women with primary biliary cirrhosis.

Aged↗
PubMed1984

The direct determination of aldosterone in human saliva.

A method is described for the direct radioimmunoassay of aldosterone in human saliva without preliminary extraction or chromatographic purification. The method has been validated with respect to sensitivity, accuracy, precision, specificity and other criteria. Under basal conditions concentrations of aldosterone in saliva ranged from 10-63% those of plasma (mean +/- SD = 32.5 +/- 13.1%). When plasma aldosterone responded to such acute stimuli as postural change, exercise or ACTH infusion, this was promptly reflected in corresponding changes in saliva aldosterone concentration. In subjects going about their normal daily business saliva aldosterone concentration fluctuated markedly during the day. It is therefore difficult to define a normal range for saliva aldosterone concentration but present observations suggest an upper limit of 150 pmol/l under basal conditions.

Aldosterone↗
PubMed1984

The action of dexamethasone and prolactin on aromatase activity in human adipose tissue.

Using slices of human adipose tissue maintained in medium 199 for 40 h at 37 degrees C, it was observed that in the absence of any other additions, the presence of foetal calf serum (10%) inhibits basal levels of aromatase activity. Including dexamethasone (1 X 10(-7) M) in the medium increases aromatase activity approximately 10-fold in the presence of foetal calf serum but has only a small stimulatory effect in its absence. The combined addition of dexamethasone (1 X 10(-7) M) and human prolactin (0.8 ng/ml) has a marked additional incremental effect in the presence or absence of foetal calf serum. In contrast, the addition of prolactin to the medium without glucocorticoid did not stimulate oestrogen production. The possibility that prolactin could be the substance in foetal calf serum responsible for mediating the stimulatory effect of glucocorticoids on oestrogen production is considered.

Adipose Tissue↗
PubMed1984

The interrelationship between plasma 5-ene adrenal androgens in normal women.

Plasma concentrations of 5-androstene-3 beta,17 beta-diol (ADIOL) dehydroepiandrosterone (DHA) dehydroepiandrosterone sulphate (DHAS) and cortisol were measured by radioimmunoassay in a group of women aged between 27 and 88 years of age. There was a significant negative correlation with increased age for all three adrenal androgens but not for cortisol. The decrease in adrenal androgens was not related to an excessive divergence from ideal body weight. There was a highly significantly positive correlation between plasma concentrations of all three adrenal androgens which supports a metabolic interrelationship.

Adult↗
PubMed1984

Adrenal androgen concentrations in breast tumours and in normal breast tissue. The relationship to oestradiol metabolism.

Concentrations of ADIOL, DHA and DHAS were measured in human breast tumours and normal tissue from the same breast and related to 17 beta-hydroxysteroid dehydrogenase (17 beta HSD) activity in these tissues. ADIOL and DHA were significantly higher in tumour tissue compared to normal tissue from the same breast (paired t-test: P less than 0.05 and P less than 0.01 respectively) whereas the difference between concentrations of DHAS in normal tissue and tumour tissue was not significant. There was a positive correlation between ADIOL and DHA in both tissues (P less than 0.001) but for DHAS the relationship was only significant in normal tissue (ADIOL:DHAS, P less than 0.001; DHA:DHAS, P less than 0.002). An increase in 17 beta-HSD activity was associated with an increase in DHAS concentrations in both normal and tumour tissue (P less than 0.01 and P less than 0.001 respectively) and with an increase in DHA concentrations in normal tissue (P less than 0.05). These results might be explained by an impairment in the balance between sulphatase and sulphotransferase activity in breast tumours.

17-Hydroxysteroid Dehydrogenases↗
PubMed1984

Aromatase activity in uterine leiomyomata.

Of the 24 samples of leiomyoma tissues examined 14 were shown to have aromatase activity in vitro. In contrast only 1 of 12 samples of myometrium had any demonstrable activity. Measurements of tissue oestrogen levels showed no correlation with the amount of aromatase activity although oestradiol levels were consistently higher in the tumour tissues compared with the normal myometrium.

Androstenedione↗