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Biomedical subjects

M J Reed

Publications and source records attributed to M J Reed.

At least 181 records · Page 10Linked to original sources
PubMed1988

Paracrine influence of human breast stromal fibroblasts on breast epithelial cells: secretion of a polypeptide which stimulates reductive 17 beta-oestradiol dehydrogenase activity.

We have previously shown that a stroma-associated paracrine influence may occur in the human breast. In particular, human breast fibroblasts secrete a factor which stimulates reductive 17 beta-oestradiol dehydrogenase (HSD) activity, thereby regulating tissue concentrations of 17 beta-oestradiol. We report here the results of experiments designed to establish the nature of the enzyme activity stimulating factor. In vitro cell culture techniques were used, in which human breast fibroblast-conditioned medium was used to grow the human breast cancer cell line, MCF-7, for 6 days, after which the reductive HSD activity of the monolayers was assessed. The fibroblastic reductive HSD stimulating factor was found to be a trypsin-sensitive polypeptide. The polypeptide eluted from a Sephadex G-75 column as a peak corresponding to a molecular weight of about 50 kDa. The polypeptide exerts its effects by altering the Vmax of 2 of the cytosolic forms of HSD within MCF-7 cells. This is achieved by a protein-synthesis-dependent but calmodulin-independent mechanism. These results provide further evidence of a paracrine effect by stromal tissue within the human breast and have important implications with respect to the aetiology and treatment of breast cancer.

17-Hydroxysteroid Dehydrogenases↗
PubMed1988

The effects of androgens and cortisol on the in vivo metabolism of oestradiol.

We have examined the effect of co-administration of dehydroepiandrosterone sulphate, 5-androstenediol or cortisol on the metabolic clearance rate of oestradiol (MCR-E2) and conversion of oestradiol to oestrone (CRE2E1). Previous studies have shown that these androgens influence the metabolism of oestradiol in vitro while cortisol alters the distribution of oestradiol in plasma. The MCR-E2 and CRE2E1 were measured after 2.5 and 5 h of [3H]oestradiol infusion with co-infusion of androgen or cortisol starting after 2.5 h of tracer infusion. For one subject who did not receive co-infusion of another steroid no significant change in MCR-E2 or CRE2E1 occurred over the 5-h period. For other subjects, however, the MCR-E2 decreased by 18 +/- 7% (mean +/- SD) while the CRE2E1 increased by 45 +/- 12%. It is possible that these results are due to: changes in the distribution of oestradiol in plasma; differences in the metabolism of oestradiol bound to albumin or SHBG, or an effect of androgens or cortisol on the uptake of [3H]oestradiol by the liver.

Aged↗
PubMed1988

Anti-androgens in gynaecological practice.

Hirsutism and acne in women are common distressing problems. Unwanted hair growth, acne and seborrhoea result from the action of androgens on the skin. Such effects depend not only on increased androgen production by the ovary or adrenal gland but also on the bioavailability of androgen to peripheral tissues. This in turn is related to transport of androgens in plasma by specific binding proteins and to peripheral metabolism of testosterone and androstenedione to their more potent 5 alpha-reduced derivatives. An effective anti-androgen is one which blocks the androgen receptor-mediated actions of testosterone and DHT on skin. CPA, the treatment of choice in the UK, is a potent androgen receptor-blocking steroid which also has progestational properties. When combined with ethinyloestradiol it also suppresses ovarian function, thus reducing androgen production, and provides effective contraception.

Acne Vulgaris↗
PubMed1988

A direct assay for oestrone sulphate and its use to investigate the effect of ampicillin on plasma levels of oestrone sulphate.

A direct radioimmunoassay for measuring plasma levels of oestrone sulphate has been developed using 8-anilino-2-naphthalene sulphonic acid to displace oestrone sulphate from plasma binding proteins. Oestrone sulphate was assayed by using an antiserum raised against glucuronide which cross-reacted 100% with oestrone sulphate. The direct assay gave a good analytical recovery of oestrone sulphate and there was a good correlation (r = 0.82, P less than 0.001) for plasma levels of oestrone sulphate measured by the direct assay and a method involving steroid conjugate extraction and enzyme hydrolysis. The mean (+/- S.D.) plasma level of oestrone sulphate in men was 1100 +/- 280 pg/ml. The effect of taking the antibiotic, Ampicillin, on plasma levels of oestrone sulphate was investigated in four men. Plasma levels of oestrone sulphate were significantly reduced after taking Ampicillin for 5 days. Ampicillin may act to lower plasma levels of oestrone sulphate by reducing the growth of bacteria in the gut or by inhibiting oestrogen sulphotransferase activity.

Ampicillin↗
PubMed1988

Mechanism and management of ovulatory failure in women with polycystic ovary syndrome.

Polycystic ovary syndrome is the most important cause of chronic anovulation. In women who fail to respond to clomiphene, low-dose FSH given in a step-wise fashion can induce normal follicular growth and ovulation. The failure of the action of endogenous FSH in these women may be related to reduced biological activity of circulating FSH, but may also involve inhibition of its action at follicular level by polypeptide growth factors such as EGF.

Androgens↗
PubMed1988

Serum androstanediol glucuronide concentrations in normal and hirsute women and patients with thyroid dysfunction.

There is currently much interest in measurements of 5 alpha-androstane-3 alpha, 17 beta-diol glucuronide (AdiolG) as a marker of peripheral androgen metabolism. We have therefore developed an assay to measure serum AdiolG levels and report that mean concentrations in hirsute (2.9 +/- 1.9 nmol/l, mean +/- SD, n = 15) and non-hirsute (1.9 +/- 0.6 nmol/l, n = 7) women with polycystic ovaries do not differ significantly from concentrations in normal women (2.2 +/- 0.8 nmol/l, n = 20). However, a correlation was found between serum AdiolG levels and Body Mass Index (r = 0.48, P less than 0.05) for women with polycystic ovaries, suggesting that weight may be an important factor in determining concentrations of this steroid conjugate. Serum AdiolG levels were significantly reduced in hypothyroid women (0.6 +/- 0.4 nmol/l, n = 5) and women receiving oral contraceptive therapy (0.6 +/- 0.4 nmol/l, n = 28) but increased in hyperthyroid women (4.0 +/- 0.6 nmol/l, n = 5). The results from this study do not support the hypothesis that serum AdiolG levels provide a marker of peripheral androgen metabolism in hirsute women and show that it is essential to exclude from such investigations any women with thyroid abnormalities or receiving oral contraceptive therapy.

Adult↗
PubMed1988

Muscle glycogen storage after different amounts of carbohydrate ingestion.

The purpose of this study was to determine whether the rate of muscle glycogen storage could be enhanced during the initial 4-h period postexercise by substantially increasing the amount of the carbohydrate consumed. Eight subjects cycled for 2 h on three separate occasions to deplete their muscle glycogen stores. Immediately and 2 h after exercise they consumed either 0 (P), 1.5 (L), or 3.0 g glucose/kg body wt (H) from a 50% glucose polymer solution. Blood samples were drawn from an antecubital vein before exercise, during exercise, and throughout recovery. Muscle biopsies were taken from the vastus lateralis immediately, 2 h, and 4 h after exercise. Blood glucose and insulin declined significantly during exercise in each of the three treatments. They remained below the preexercise concentrations during recovery in the P treatment but increased significantly above the preexercise concentrations during the L and H treatments. By the end of the 4 h-recovery period, blood glucose and insulin were still significantly above the preexercise concentrations in both treatments. Muscle glycogen storage was significantly increased above the basal rate (P, 0.5 mumol.g wet wt-1.h-1) after ingestion of either glucose polymer supplement. The rates of muscle glycogen storage, however, were not different between the L and H treatments during the first 2 h (L, 5.2 +/- 0.9 vs. H, 5.8 +/- 0.7 mumol.g wet wt-1.h-1) or the second 2 h of recovery (L, 4.0 +/- 0.9 vs. H, 4.5 +/- 0.6 mumol.g wet wt-1. h-1).(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Glucose↗
PubMed1988

Oestradiol assays: applications and guidelines for the provision of a clinical biochemistry service.

This paper reports on the provision of a clinical biochemistry service for serum oestradiol. The pathophysiology and recognised applications of oestradiol assays are discussed and the current availability of assay reagents and methodologies reviewed. Data are presented on the analytical performance of assays for serum oestradiol in the UK External Quality Assessment Scheme (UKEQAS) and general guidance is offered to laboratories providing a diagnostic service for this analyte.

Adult↗
PubMed1988

Serum 11 beta-hydroxyandrostenedione as an indicator of the source of excess androgen production in women with polycystic ovaries.

Serum 11 beta-hydroxyandrostenedione levels (11-OHA) were measured in normal women and women with polycystic ovaries (PCO) to assess their value in localizing the source of excessive androgen production in women with PCO. Serum 11-OHA was undetectable (less than 1.5 nmol/L) in an adrenalectomized woman, a woman with 11-hydroxylase deficiency, and a woman receiving chronic dexamethasone therapy, confirming the specificity of the antiserum used in this study. Serum 11-OHA concentrations were similar in normal women [mean, 5.0 +/- 2.3 (+/- SD) nmol/L] and women with PCO (5.0 +/- 2.1 nmol/L); serum androstenedione concentrations were increased in women with PCO. Thus, the ratio of androstenedione to 11-OHA was significantly higher (P less than 0.001) in women with PCO (2.0 +/- 0.7) than in normal women (1.1 +/- 0.5). Serum 11-OHA levels after adrenal suppression or stimulation were similar in women with PCO who had an ovulatory response and those who failed to ovulate after clomiphene administration. Administration of dexamethasone (1 mg) and injection of ACTH (250 micrograms) were associated with marked suppression and subsequent stimulation of serum 11-OHA levels in both normal women and women with PCO, and the responses were similar in the two groups. Also, the hour to hour and diurnal variations in serum 11-OHA were similar to those of androstenedione and cortisol during a 24-h period, indicating the adrenal origin of 11-OHA. Our finding of similar serum 11-OHA levels in the presence of increased serum androstenedione levels in women with PCO supports the concept that the ovary is the major source of excess androgen production in women with PCO.

Adrenal Glands↗
PubMed1988

Androstenedione concentrations following dexamethasone suppression: correlation with clomiphene responsiveness in women with polycystic ovary syndrome.

It is difficult to predict clomiphene responsiveness in women with polycystic ovary syndrome (PCOS) but it has been suggested that women with evidence of excess adrenal androgen are less likely to respond to clomiphene. To investigate this further we performed a short Synacthen test following overnight dexamethasone suppression, using 11 beta-hydroxyandrostenedione (11-OHA) as a specific marker of adrenal androgen secretion in women with anovulatory infertility due to PCOS (n = 19) compared with a normal group (n = 7). Women with PCOS were subsequently divided into 2 groups according to whether or not they ovulated after clomiphene. On day 1 blood was taken at 9.00 hours for measurement of androstenedione (A), 11-OHA and cortisol, and 1 mg dexamethasone was given at 22.00 hours. On day 2 blood was taken at 9.00 hours and at 30 and 60 minutes after intravenous administration of 250 micrograms Synacthen. Before dexamethasone was given, concentrations of A but not of 11-OHA or cortisol were significantly higher in women with PCOS than in controls but there was no difference in A levels between clomiphene responders and non-responders. After 1 mg dexamethasone had been given, concentrations of A, 11-OHA and cortisol were suppressed in all 3 groups and there were no differences between the groups in the post-dexamethasone concentrations of 11-OHA or cortisol.(ABSTRACT TRUNCATED AT 250 WORDS)

Amenorrhea↗
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↗