Biomedical subjects

V H James

Publications and source records attributed to V H James.

At least 55 records · Page 3Linked to original sources

PubMed1987

Determination of dehydroepiandrosterone and dehydroepiandrosterone sulphate in blood and tissue. Studies of normal women and women with breast or endometrial cancer.

Radioimmunoassay methods for measuring dehydroepiandrosterone (DHA) and its sulphate (DHAS) in human plasma and tissues were developed and validated. Plasma levels were measured in men, pre- and postmenopausal women, and patients with endometrial or breast cancer. In the patients, tissue concentrations were also measured. Plasma DHA levels fluctuated synchronously with cortisol, but DHAS levels were less labile, and reached maximum levels during the day and were lowest at night. No obvious pattern was seen in relation to the menstrual cycle. Both DHA and DHAS levels fell with age, but DHA levels reached a plateau at about 60 years. No significant effect of weight on plasma levels was found. Plasma levels in the cancer patients were not significantly different from age-matched controls either when single samples were compared, or when mean 24 h levels were used. Endometrial tissue levels of DHA fell with age, unlike DHAS. In breast tumour tissue, DHA, but not DHAS concentrations were higher than in normal breast tissue. A good correlation between plasma and tissue DHAS levels was found, and DHA levels were also correlated in plasma and tissue. The correlations between plasma and tissue were not observed in tumour tissue, which may be due to altered tissue metabolism.

Adult↗

PubMed1987

Diurnal fluctuation in saliva aldosterone concentration.

We have measured saliva aldosterone concentration (SA) at frequent intervals in subjects going about their normal daytime activities. Four hourly sampling sufficed to give a reasonable estimate of mean diurnal SA but hourly sampling is necessary if it is desired to study the temporal pattern of SA. In subjects with normal or elevated mean levels, SA fluctuated considerably suggestive of several distinct episodes of aldosterone secretion. Such fluctuations show little correlation with the concentrations in saliva of glucocorticoids (cortisol + cortisone) nor are they consistent with a circadian rhythm of aldosterone secretion. We suggest that they may represent responses to such stimuli as eating, drinking or physical activity, and possibly to other as yet unidentified factors. These observations show the importance of comprehensive diurnal assessment of aldosterone level in physiological and pathological investigations. Because of its non-invasive nature and the high productivity of the assay, measurement of SA is ideally suited for this purpose.

Aldosterone↗

PubMed1987

Peripheral oestrogen metabolism in postmenopausal women with or without breast cancer: the role of dietary lipids and growth factors.

Studies we have carried out have revealed significant differences in oestrogen production and metabolism between normal women and postmenopausal women with breast cancer. The free, biologically available fraction of oestradiol is elevated in plasma from women with breast cancer and we have found that metabolic clearance rates and production rates of oestradiol are also increased. In vitro studies have suggested that lipids can influence the distribution of sex steroids in plasma and we have therefore examined the effect of dietary lipids on the distribution of sex steroids in plasma in vivo. Consumption of a meal with a high saturated fat content or the oral or i.v. administration of "Intralipid", a stabilised emulsion of soya bean oil that is high in unsaturated free fatty acids, had little effect on the available fractions of oestradiol in plasma. However, results from a preliminary study suggest that long-term changes in dietary fat intake can alter the distribution of steroids in plasma. It is concluded that dietary lipids may influence the availability of sex steroids to tissues. Such a mechanism could account for the significant correlation that has been found between dietary fat consumption and the incidence of breast cancer on a world-wide basis.

Breast Neoplasms↗

PubMed1987

The distribution of oestradiol in plasma in relation to uterine cross-sectional area in women with polycystic or multifollicular ovaries.

The uterine cross-sectional area (UXA) of women with polycystic (PCO) or multifollicular ovaries (MFO) is significantly larger and smaller, respectively, than those of normal women during the early-mid-follicular phase of the menstrual cycle. In the present study the distribution of oestradiol in plasma from normal women and women with PCO or MFO was measured to determine if differences in the available fractions of oestradiol could account for the differences in UXA of women with PCO or MFO. No differences in plasma levels of oestradiol were detected and the concentrations of oestradiol present in a free state or bound to albumin were similar in normal women and women with PCO or MFO. The concentration of oestrone was significantly higher in plasma from women with PCO (516 +/- 120 pmol/l, mean +/- SD) than in plasma from women with MFO (389 +/- 91 pmol/l) or normal women (376 +/- 89 pmol/l). Differences in UXA for women with PCO or MFO as compared with normal women cannot therefore be attributed to differences in available oestradiol concentrations. It is possible that abnormalities in oestrogen metabolism within uterine or other tissues may account for the UXA of women with PCO or MFO. Increased plasma oestrone levels in women with PCO may provide more substrate for conversion to oestradiol within the uterus whilst the smaller UXA of women with MFO may reflect both lack of normal cyclical increases of oestradiol and formation of biologically inactive oestradiol metabolites.

Body Constitution↗

PubMed1987

Dietary lipids: an additional regulator of plasma levels of sex hormone binding globulin.

The effect of dietary lipid consumption on plasma levels of sex-hormone binding globulin (SHBG), free testosterone and cholesterol was studied in 6 normal men. After consuming a diet with a high fat content (greater than 100 g fat/day) for two weeks, the mean plasma cholesterol level increased (p less than 0.02) while the mean SHBG level decreased (p less than 0.02). Changing the diet from one with a high fat to low fat content (less than 20 g fat/day) for a further two week period resulted in a significant reduction in mean plasma cholesterol level (p less than 0.001) while the mean SHBG level increased (p less than 0.01). The increase in plasma SHBG was associated with a significant decrease in the free testosterone fraction and free testosterone concentration. No significant changes were detected in plasma samples obtained from the same men during a control period. The results from this study demonstrate that dietary lipid intake is an additional factor involved in the regulation of plasma levels of SHBG.

Adult↗

PubMed1986

A comparison of the in vivo uptake and metabolism of 3H-oestrone and 3H-oestradiol by normal breast and breast tumour tissues in post-menopausal women.

After infusion of 3H-oestradiol or 3H-oestrone into post-menopausal women with breast cancer, there was a significant uptake of both steroids by breast tumour and normal tissue. The proportion of oestrogen present in tumour tissue as 3H-oestradiol after infusion of 3H-oestradiol (89.4 +/- 3.5%, mean +/- SD, n = 4) was significantly higher (p less than 0.001) than in normal breast tissue (72.8 +/- 3.3%) obtained from the same women. Similarly, after infusion of 3H-oestrone, the proportion of oestrogen present as 3H-oestradiol (48.4 +/- 14.4%) was significantly higher than in normal breast tissue (19.1 +/- 6.4%). These results suggest that conversion of oestrone to oestradiol is enhanced in breast tumour tissue with little metabolism of oestradiol. This would account for the higher concentrations of oestradiol reported in breast tumour tissue in the presence of increased oestradiol 17 beta-hydroxysteroid dehydrogenase activity.

Aged↗

PubMed1986

The regulation of the biologically available fractions of oestradiol and testosterone in plasma.

The albumin bound fractions of oestradiol and testosterone have been measured in samples of plasma obtained over a 24 h period from women with breast cancer or polycystic ovarian disease and from pre- and postmenopausal control subjects and related to plasma levels of free fatty acids. For most subjects changes in the fraction of oestradiol bound to albumin were related to changes in plasma levels of free fatty acids. A significant decrease in the albumin bound testosterone fraction during the night was associated with increased plasma levels of cortisol.

Biological Availability↗

PubMed1986

Metabolism of [3H]oestradiol in vivo by normal breast and tumour tissue in postmenopausal women.

Tumour and normal breast tissue was obtained from postmenopausal breast cancer patients following [3H]oestradiol infusion (50 mu Ci over a 12 h period). The fraction of radioactivity present as oestradiol or oestrone was measured and the results expressed both as the ratio of oestradiol-oestrone and as the percentage oestrogen present as oestrone, and the findings compared with in vitro measurements of 17 beta-hydroxysteroid dehydrogenase activity. Concentrations of 5-androstene-3 beta, 17 beta-diol, dehydroepiandrosterone and its sulphate and testosterone were measured and related to oestradiol metabolism. The study demonstrated that tumour tissue is less able to metabolise oestradiol to oestrone than is normal breast tissue and indicated that the ability of the tissue to detoxify oestradiol may be dependent on cofactor availability. The results also supported the possibility that increased tissue concentrations of adrenal androgens inhibit oestradiol and thus increase tissue exposure to oestradiol.

Aged↗

PubMed1986

Free fatty acids: a possible regulator of the available oestradiol fractions in plasma.

Consumption of dietary fats has been linked to the high incidence of breast cancer found in Western women. In vitro studies we have carried out show that unsaturated free fatty acids can increase the biologically available oestradiol fractions in plasma. It is possible therefore that the increased risk for breast cancer associated with a diet high in fats may be related to an elevation in the biologically available oestradiol fractions in plasma.

Dietary Fats↗

PubMed1986

The role of tissue steroids in regulating aromatase and oestradiol 17 beta-hydroxysteroid dehydrogenase activities in breast and endometrial cancer.

We have observed that oestradiol concentrations in breast and endometrial tumours are relatively higher than oestrone, in contrast to peripheral tissues. Infusion of radiolabelled oestrogen also suggested there was a difference in metabolism between normal and tumour tissue. We have therefore looked for factors which could modulate tissue steroid metabolism and conclude that progesterone may influence aromatase, and that the adrenal androgens can inhibit oestradiol dehydrogenase activity. The latter mechanism, in particular, may be important in increasing tissue exposure to oestradiol.

Aromatase↗

PubMed1986

Aromatase activity and concentrations of cortisol, progesterone and testosterone in breast and abdominal adipose tissue.

Aromatase activity and concentrations of cortisol, progesterone and testosterone were measured in samples of breast and abdominal adipose tissue obtained from both pre- and postmenopausal subjects. Enzyme activity was determined by the incorporation of tritium from [1 beta-3H]androstenedione into water and found to be in close agreement to that measured when tritium labelled oestrone (E1) and oestradiol (E2) were isolated. No significant difference in enzyme activity was noted between breast and abdominal adipose tissue. Increased aromatase activity was not observed in adipose tissue taken from a subject with endometrial cancer. Cortisol concentrations were found to be significantly higher (P less than 0.05) in abdominal as compared to breast tissue. Without attaining statistical significance progesterone concentrations were higher in abdominal as compared to breast adipose tissue. Aromatase activity was not related to either cortisol or testosterone tissue concentration, but an inverse relationship between progesterone concentration and aromatase activity was observed (r = 0.542, P less than 0.02). On the basis of results obtained a hypothesis for the increased conversion of androgen to oestrogen as seen after the menopause has been proposed.

Abdomen↗

PubMed1986

The relationship between oestradiol metabolism and adrenal steroids in the endometrium of postmenopausal women with and without endometrial cancer.

The aim of the present study was to investigate the hypothesis that adrenal androgens are contributory to the development of endometrial cancer either by the oestrogenic action of 5-androstene-3 beta, 17 beta-diol (androstenediol) or through the inhibition of oestradiol metabolism. Concentrations of androstenediol, dehydroepiandrosterone (DHA), DHA sulphate (DHAS), oestrone and oestradiol were measured in plasma and endometrium from postmenopausal women with and without endometrial cancer. There was no difference between normal postmenopausal women and endometrial cancer patients with respect to either tissue or plasma adrenal androgens although there was a tendency for plasma DHAS levels to be increased in cancer patients (normal women: 640 +/- 156 ng/ml; cancer patients: 808 +/- 159 ng/ml). There was a positive correlation between endometrial tissue concentrations of androstenediol and DHA in both normal women (P less than 0.05) and cancer patients (P less than 0.01) but for DHAS the relationship was only significant for non-malignant tissue (androstenediol: DHAS, P less than 0.05; DHA: DHAS, P less than 0.02). A significant positive correlation was found between all three plasma adrenal androgens for both groups. In cancer patients there was a trend towards an inverse correlation between endometrial tissue concentrations of DHAS and the enzyme 17 beta-hydroxysteroid dehydrogenase (17OHSD) although the relationship was not significant (r = 0.49). In endometrium, oestradiol was present in significantly higher concentrations than oestrone whereas in plasma the reverse was the case. There was also a tendency for plasma oestradiol levels to be elevated in the cancer subjects. These data do not support a substantial role for adrenal androgens in endometrial cancer but suggest that a relationship may exist between DHAS and 17OHSD and that an imbalance between sulphatase and sulphotransferase activities may be involved.

17-Hydroxysteroid Dehydrogenases↗

PubMed1986

Estrogen production and metabolism in normal postmenopausal women and postmenopausal women with breast or endometrial cancer.

The metabolic clearance rates of estradiol in postmenopausal women with breast cancer (1269 +/- 370 1/24 hr, mean +/- S.D.) or endometrial cancer (1320 +/- 238 1/24 hr) were significantly higher than in normal postmenopausal women (922 +/- 238 1/24 hr). The metabolic clearance rates of estrone were elevated in women with endometrial cancer (2012 +/- 749 1/24 hr) or with conditions associated with an increased risk for breast or endometrial cancer (1830 +/- 413 1/24 hr) compared with values for normal postmenopausal women (1321 +/- 301 1/24 hr). The production rate of estradiol was only increased in women with breast cancer. Significant correlations were found between subjects' percentage of ideal body wt and the metabolic clearance rates of estrone and estradiol and also the production rate of estrone. The increased clearance rates may reflect differences in either the binding of estrogens to plasma proteins or the tissue metabolism of estrogens in cancer patients.

Aged↗

PubMed1986

The effect of epidermal growth factor, transforming growth factor and breast tumour homogenates on the activity of oestradiol 17 beta hydroxysteroid dehydrogenase in cultured adipose tissue.

The effect of epidermal growth factor (EGF), transforming growth factor (TGF alpha) and breast tumour homogenates on oestradiol 17 beta hydroxysteroid dehydrogenase (E2DH) activity has been examined using cultured human breast adipose tissue. EGF (100-1000 ng/ml) inhibited E2DH activity (E1----E2) in a dose dependent manner. TGF alpha (250 and 500 ng/ml) stimulated E2DH activity, with conversion of E1----E2 increasing to a greater degree than E2----E1 activity. Breast tumour homogenates (2-10% w/v) also influenced E2DH activity. It is concluded that growth factors, produced by breast tumours, may modulate E2DH activity in tissues surrounding the tumour and thereby influence tumour growth.

17-Hydroxysteroid Dehydrogenases↗

PubMed1986

Oestrogen production and metabolism in peri-menopausal women.

The metabolic clearance rates and production rates of oestrone and oestradiol have been measured in a group of peri-menopausal women either with breast or endometrial cancer or having an increased risk of developing one of these diseases. The results were compared with values for normal post-menopausal women in whom the menopause was established. The transfer constants for the conversion of oestrone to oestradiol and of oestradiol to oestrone were also measured. Metabolic clearance rates for oestrone (1946 +/- 406 1/24 h) and oestradiol (1296 +/- 261 1/24 h) for peri-menopausal women, and production rates of oestrone (90 +/- 38 micrograms/24 h) and oestradiol (45 +/- 33 micrograms/24 h) were significantly higher than for normal post-menopausal women. Transfer constants for the conversion of oestrone to oestradiol and of oestradiol to oestrone were similar in the peri- and post-menopausal women. Plasma progesterone concentrations were less than 0.4 ng/ml in both groups of women. It is possible that the higher oestrogen production and clearance rates of peri-menopausal women, at a time when progesterone production is greatly reduced, may in part account for the higher risk that post-menopausal women have for developing breast or endometrial cancer.

Breast Neoplasms↗

PubMed1986

The effect of glucocorticoids on the in vivo conversion of androstenedione to oestrone.

In vitro studies have previously shown that the activity of the aromatase enzyme system, which is responsible for the conversion of androstenedione to oestrone, can be stimulated by natural and synthetic glucocorticoids and also by ACTH. In view of the potential physiological importance of such a regulatory mechanism we have examined the effect of administration of dexamethasone, and of ACTH on the conversion of androstenedione to oestrone in vivo. The transfer constants for the conversion of androstenedione to oestrone [( rho]AEBU) measured in two women before administration of dexamethasone were 1.0% and 1.1% and after were 0.9% and 1.2%. Similarly no increase in conversion of androstenedione to oestrone [( rho]AE1BB) was detected after ACTH stimulation (pre = 0.74%, post = 0.77%). It is concluded from this study that glucocorticoids and ACTH do not have a role in regulating aromatase activity in vivo.

Adrenocorticotropic Hormone↗

PubMed1986

The use of nonradiolabelled steroid infusions to investigate the origin of oestrone sulphate in postmenopausal women.

Infusion of nonradiolabelled dehydroepiandrosterone sulphate (DHA-S) has been used to investigate the possible formation of oestrone sulphate via a sulphated conjugate of androstenedione. The metabolic clearance rate (MCR) of DHA-S also was measured and the mean value (25 1/24h) was similar to values reported using isotopic techniques. Although conversion of DHA-S to 5-androstenediol, a steroid with oestrogenic properties, was detected during infusion of DHA-S, there were no significant increases in plasma levels of conjugated androstenedione or oestrone sulphate. The MCR's oestrone sulphate measured using infusion of nonradiolabelled steroid in two menopausal women were 99 1/24h and 121 1/24h. For one woman, the production rate of oestrone sulphate, calculated from the conversion of oestrone and oestradiol to oestrone sulphate (151 nmol/day) was similar to the measured production rate of oestrone sulphate (144 nmol/day). It is concluded that in menopausal women, oestrone sulphate is derived from conversion of oestrone and oestradiol with no formation occurring via conjugated androstenedione.

Androstenediols↗

PubMed1986

The relationship between salivary aldosterone and plasma free aldosterone concentrations.

The proportion of aldosterone in plasma not bound to proteins (% plasma free aldosterone, %PFA) was measured using an equilibrium dialysis technique and was found to lie predominantly in the range 25-40% although extremes of 20% and 60% were encountered. From this value and the total concentration of aldosterone in plasma (plasma aldosterone, PA) the concentration of free aldosterone in plasma (PFA) was calculated. Percentage PFA was not affected by the in-vitro addition of aldosterone (up to the equivalent of 2000 pmol/l) but the incremental addition of cortisol (up to the equivalent of 550 nmol/l) resulted in a linear increase in % PFA from 26% to 34%. Percentage PFA was found to be significantly, negatively correlated with serum albumin concentration (r = -0.87; P less than 0.001) but it was only when this was less than 15 milligrams that % PFA was abnormally high. Salivary aldosterone concentration (SA) was more highly correlated with PFA (r = 0.84) than with PA (r = 0.75), which indicates that even modest variance in %PFA has a discernible effect upon the overall SA-PA relationship. We conclude that measurement of salivary aldosterone concentrations gives a useful estimate of plasma free aldosterone level. Variations in the latter are determined more by changes in the total concentration of aldosterone in plasma than by variations in the degree of binding by plasma proteins.

Albumins↗