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Biomedical subjects

M J Reed

Publications and source records attributed to M J Reed.

At least 199 records · Page 11Linked to original sources
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

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↗
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

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

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↗