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Biomedical subjects

V H James

Publications and source records attributed to V H James.

At least 91 records · Page 5Linked to original sources
PubMed1984

17 Beta-hydroxysteroid dehydrogenase and aromatase activity in breast fat from women with benign and malignant breast tumours.

The activity of 17 beta-hydroxysteroid dehydrogenase and aromatase was studied in adipose tissue taken from women aged between 22 and 83 years with benign or malignant breast lesions. The benign and malignant groups showed no significant differences in the mean activities of either of the enzymes studied. Under the experimental conditions used, the rate of conversion of oestrone to oestradiol varied markedly between subjects (6-169 ng oestradiol/mg protein/h), and there was a positive correlation between oestrone reduction and the total body weight of the tissue donor. In contrast, although the apparent Km for oestradiol (0.1-2.6 mumol/l) was lower than that for oestrone (9-14 mumol/l) the maximum velocity for oestrone production was very low (10-50 pmol/mg protein/h), and there was no obvious correlation with the age or body weight of the tissue donor. Aromatase activity in breast fat was at the lower end of the normal range of activity previously reported for abdominal adipose tissue, and there was no correlation between oestrone production and age or body weight.

17-Hydroxysteroid Dehydrogenases↗
PubMed1984

Adrenal androgen concentrations in endometrium and plasma during the menstrual cycle.

Concentrations of 5-androstene-3 beta, 17 beta-diol (androstenediol), dehydroepiandrosterone (DHA) and DHA sulphate (DHAS) were measured in endometrium and plasma from normal premenopausal and perimenopausal women (average ages 37 and 48 years respectively) at different stages of the menstrual cycle. Plasma levels did not vary with the stage of the cycle for any of the three steroids. Mean plasma levels of androstenediol ranged between 2.03 and 2.92 nmol/l for premenopausal women and 1.38 and 1.58 nmol/l for perimenopausal women while mean concentrations of DHA were 20.80-36.41 nmol/l (premenopausal women) and 13.87-19.07 nmol/l (perimenopausal women). The values for DHAS were more variable and ranged between 3.20 and 4.56 and 2.94 and 4.25 mumol/l for pre- and perimenopausal women respectively. In premenopausal women endometrial tissue concentrations of androstenediol and DHA increased three to fourfold in the secretory phase while no increase was observed in DHAS. There was a similar increase in androstenediol but not DHA or DHAS during the secretory phase for perimenopausal women. A significant positive correlation was found for tissue androstenediol and DHA in both groups of women but the relationship between DHAS and the other androgens was significant only for perimenopausal women. We suggest that the increase in androstenediol and DHA concentrations could be due to an increase in a receptor or binding protein, possibly progesterone dependent, present in secretory phase endometrium.

Adult↗
PubMed1983

Aromatization of steroids in peripheral tissues.

The action of glucocorticoids on aromatase activity in human adipose tissue has been investigated. Oestrogen production was increased in tissue maintained in the presence of dexamethasone and cortisol. Dexamethasone was effective at concentrations as low as 1 nmol/l. In contrast, over the 40 h incubation period, cortisol was only effective at concentrations in excess of 500 nmol/l, although after conditions of prolonged incubation, induction of aromatase activity was measurable using cortisol concentrations as low as 28 nmol/l. There were apparent variations in both basal levels of aromatic activity and in response to glucocorticoids in adipose tissue taken from various sites within the body.

Adipose Tissue↗
PubMed1983

Inhibition of 17 beta-hydroxysteroid dehydrogenase activity in human endometrium by adrenal androgens.

The effect of dehydroepiandrosterone sulphate (DHA-S) and its metabolites dehydroepiandrosterone (DHA) and 5-androstene-3 beta, 17 beta-diol (ADIOL) on the activity of 17 beta-hydroxysteroid dehydrogenase in human endometrial tissue was investigated by an isotope ratio technique. The apparent KM for oestradiol was 1.59 X 10(-6) M. All three androgens inhibited the metabolism of oestradiol and the apparent Ki values were: ADIOL, 2.05 X 10(-6) M; DHA-S and DHA, 1.59 X 10(-6) M. However, ADIOL acted by direct competition with oestradiol for the active enzyme site whereas inhibition by DHA and its sulphate was non-competitive. DHA-S and DHA were more potent inhibitors of oestradiol metabolism than was ADIOL. These results support the hypothesis that adrenal androgens could be involved in the development of endometrial hyperplasia and adenocarcinoma. Inhibition of oestradiol metabolism could increase the concentration of oestradiol in endometrial tissue and if unopposed by progesterone, e.g. after the menopause or in subjects with ovulatory defects, could stimulate abnormal endometrial growth.

17-Hydroxysteroid Dehydrogenases↗
PubMed1983

Endometrial tissue and plasma concentrations of 5-androstene-3 beta, 17 beta-diol during the menstrual cycle in normal premenopausal and perimenopausal women.

A radioimmunoassay for 5-androstene-3 beta, 17 beta-diol (ADIOL) in human endometrium and plasma is described. The recognised criteria of reliability have been fulfilled. Plasma and endometrial tissue concentrations of ADIOL were determined in samples obtained from normal premenopausal and perimenopausal women (average ages 37 and 48 years respectively) at different phases of the menstrual cycle. In perimenopausal women plasma concentrations of ADIOL did not vary throughout the cycle (proliferative phase: 411 +/- 95 (SEM) pg/ml; secretory phase: 462 +/- 28.5 (SEM) pg/ml). For the premenopausal group the pattern was similar (proliferative phase: 568.4 +/- 56.9 (SEM) pg/ml; secretory phase: 663.1 +/- 64.7 (SEM) pg/ml) although a significant difference (P less than 0.05) was noted between late proliferative and late secretory phase levels in these women. A different pattern was observed for endometrial tissue concentrations of ADIOL. In both groups of women a significant (3-4-fold) increase occurred during the secretory phase. There was no apparent relationship between plasma and tissue concentrations of ADIOL either during the proliferative or the secretory phase. There was, however, an age associated decrease for both tissue and plasma ADIOL. Theories are proposed to account for the increase in ADIOL concentration during the luteal phase.

Adult↗
PubMed1983

Inhibition of 3-beta-hydroxy steroid dehydrogenase activity in first trimester human pregnancy with trilostane and WIN 32729.

The effects of equivalent doses of two inhibitors of the 3-beta-hydroxy steroid dehydrogenase enzyme system--WIN 24540 (trilostane) and WIN 32729--on the secretion of progesterone in early human pregnancy are described. Patients and controls less than 12 weeks pregnant were given a single dose of either drug and the resultant hormonal changes monitored for 7 1/2 h. A consistent fall in plasma progesterone concentrations occurred at all doses and, at the highest dose, they fell to less than 50% of pre-treatment levels. However, whilst with trilostane the associated increase in plasma concentrations of pregnenolone was always accompanied by a rise in plasma DHA concentrations, with WIN 32729 there appeared to be no adrenal effect at the lower dosage levels. These data demonstrate inhibition of progesterone secretion in human pregnancy using non-hormonally active steroids. The pattern of steroid precursors indicates that while both drugs inhibit 3-beta-hydroxy steroid dehydrogenase activity, WIN 32729 is more selective and only interferes with adrenal steroid biosynthesis at high doses.

3-Hydroxysteroid Dehydrogenases↗
PubMed1983

The relationship between 17 beta-hydroxysteroid dehydrogenase activity and oestrogen concentrations in human breast tumours and in normal breast tissue.

The activity of 17 beta-hydroxysteroid dehydrogenase (17 beta HSD) was measured in human breast tumours and in normal breast tissue from premenopausal, perimenopausal and postmenopausal women. Enzyme activity was higher in tumour tissue than in normal tissue from the same breast and under the conditions of the assay the oxidation of oestradiol was higher than the reduction of oestrone. The physiological status of the women in the study did not relate to the activity of the enzyme in either normal or tumour tissue although fibroadenomas had less activity than adenocarcinomas. In postmenopausal women tumour tissue oestrogens were 2-3 fold higher than in normal tissue from the same breast. Furthermore, tumour tissue concentrations of oestradiol tended to be higher than those of oestrone although in normal tissue the two oestrogens were present in similar concentrations. In plasma from the same women oestrone was the predominant oestrogen. There appears to be no direct relationship between 17 beta HSD activity and oestrogen concentrations but the enzyme may play a part in determining the balance between oestrone and oestradiol according to substrate and cofactor availability.

17-Hydroxysteroid Dehydrogenases↗
PubMed1983

Plasma and salivary androstenedione and dihydrotestosterone in women with hyperandrogenism.

Sensitive radioimmunoassays (RIA) have been developed to measure salivary and plasma androstenedione and dihydrotestosterone levels in normal women, women with polycystic ovaries (PCO) and idiopathic hirsutism, and patients on antiandrogen therapy. There was a highly significant correlation (r = 0.92, P less than 0.001) between the concentration of androstenedione in saliva and the unbound concentration in plasma. The unbound plasma androstenedione was measured in the dialysate by RIA and ranged from 6.0-10.4% of the total concentration. Salivary and plasma androstenedione levels in patients with PCO (185 +/- 72 pg/ml (n = 11) and 3262 +/- 814 pg/ml (n = 12) respectively) and in those with hirsutism (151 +/- 110 pg/ml (n = 25) and 2177 +/- 1096 pg/ml (n = 25) were significantly higher than levels in normal women (78 +/- 30 pg/ml (n = 18) and 787 +/- 355 pg/ml (n = 18). A good correlation (r = 0.82, P less than 0.001) was also found between salivary and unbound plasma dihydrotestosterone concentrations. Salivary and plasma dihydrotestosterone levels in patients with PCO (8.2 +/- 3.3 pg/ml (n = 9) and 167 +/- 45 pg/ml (n = 11) respectively and hirsutism (6.0 +/- 2.1 pg/ml (n = 14) and 176 +/- 69 pg/ml (n = 17) were significantly higher than levels in normal women (4.5 +/- 1.3 pg/ml (n = 17) and 90 +/- 44 pg/ml (n = 16), although there was a large overlap between groups. A similar decrease was observed in salivary and plasma androstenedione levels after treatment with cyproterone acetate (CA) and ethinyl oestradiol (EE) for 3 months. Plasma dihydrotestosterone levels remained elevated in 47% of treated women whereas only 21% of cases had raised salivary dihydrotestosterone levels. It is concluded that, as with testosterone salivary androstenedione and dihydrotestosterone measurements give a good reflection of their biologically active levels in normal, hyperandrogenic and CA + EE treated women.

Adolescent↗
PubMed1983

Plasma levels of estrone, estrone sulfate, and estradiol and the percentage of unbound estradiol in postmenopausal women with and without breast disease.

To investigate the possibility of increased tissue exposure to estrogen in breast cancer patients, plasma levels of estrogens and the percentage of unbound estradiol were measured in postmenopausal women with benign or malignant breast disease and compared with levels in normal postmenopausal women. The percentage of unbound estradiol in breast cancer patients [1.85 +/- 0.35% (S.D.)] was significantly higher (p less than 0.001) than in normal postmenopausal women [1.52 +/- 0.33%] and was still significantly higher when patients were matched with control subjects for weight (p less than 0.001) or ideal body weight (p less than 0.001). The binding capacity of sex hormone binding globulin was similar in both groups of women. No significant differences in the plasma levels of estrone, estradiol, or estrone sulfate were detected between breast cancer and normal subjects. It is concluded that, given similar concentrations of estradiol in plasma of normal and breast cancer subjects, the significant increase found in the unbound estradiol fraction may result in a very small increment in tissue exposure to estrogens in breast cancer subjects. However, even such a small increase in tissue exposure to estradiol may be significant, given the length of time required for breast tumor development.

Aged↗
PubMed1982

Studies on the activity of 17 beta-hydroxysteroid dehydrogenase in human adipose tissue.

The activity of 17 beta-hydroxysteroid dehydrogenase has been investigated in human subcutaneous adipose tissue. Using oestrone as substrate, oestradiol formation was linear with time and the concentration of protein in the tissue homogenate. The optimum pH was 8.0 and the Km for oestrone was 2.5 x 10(-6) M. With NADH, the production of oestradiol was about 30% of that with NADPH. Oestradiol was also a substrate for the enzyme although under the experimental conditions used reduction of oestrone appeared to be favoured in adipose tissue. In the presence of progesterone (31.8 x 10(-6) M) the Km for oestrone was increased fivefold.

17-Hydroxysteroid Dehydrogenases↗
PubMed1982

Oestrogen production in adipose tissue from normal women and women with endometrial cancer in vitro.

The in vitro conversion of androstenedione to oestrone and oestrone to oestradiol was investigated in human adipose tissue. Higher rates of oestrone (range 1.2-44.0 pg/mg protein/3h) and oestradiol (range 0.6-15.2 ng/mg protein/h) production were observed in tissue samples obtained from women aged 40-50 years compared with the rates measured using adipose tissue from younger women (range 0.7-7.7 pg oestrone/mg protein/3 h and 0.4-1.8 ng oestradiol/mg protein/h). Five subjects studied with endometrial cancer did not show a market increase in conversion of androstenedione to oestrone or oestrone to oestradiol in subcutaneous adipose tissue compared with normal women of similar age and weight. A sample of omental adipose tissue from one subject with endometrial cancer did show a high conversion rate of androstenedione to oestrone (104.0 pg oestrone/mg protein/3 h), although the rate of conversion of oestrone to oestradiol was lower than that observed in subcutaneous adipose tissue, indicating that steroid metabolism is not uniform in adipose tissue throughout the body.

Adipose Tissue↗
PubMed1982

Salivary testosterone: relationship to unbound plasma testosterone in normal and hyperandrogenic women.

A sensitive radioimmunoassay (RIA) was used to measure salivary testosterone levels in normal women, in patients with polycystic ovaries (PCO), and in women with hirsutism. There was a highly significant correlation (r = 0.79, P less than 0.001) between the concentration of testosterone in saliva [12.3 +/- 7.8 (SD) pg/ml] and the concentration of unbound testosterone in plasma (5.2 +/- 3.1 pg/ml) in matched samples collected from 56 women including normals, patients with clinical signs of hyperandrogenism, and women treated with a combination of cyproterone acetate (CA) and ethinyl oestradiol (EE). The unbound plasma testosterone was measured in the dialysate directly using a sensitive RIA. Salivary and plasma testosterone levels in patients with PCO (20.6 +/- 8.5 and 626 +/- 187 pg/ml respectively, n = 14) and in those with hirsutism (13.9 +/- 5.6 and 421 +/- 170 pg/ml, n = 30) were significantly higher (P less than 0.001) than levels in normal women (7.7 +/- 2.6 and 196 +/- 68 pg/ml, n = 36). Treatment for 3 months with CA and EE resulted in a decrease (mean 68%) in salivary testosterone levels in all patients studied (n = 15), but the suppression of plasma testosterone (mean 34%) was not observed in all cases. It is concluded that measurement of salivary testosterone gives a useful indication of levels of biologically available androgen in hyperandrogenic women, before and during CA/EE therapy.

Adolescent↗
PubMed1982

Failure of FSH to influence aromatization in human adipose tissue.

Since gonadotrophins are known to influence aromatase activity in gonadal tissue, an attempt was made to correlate serum gonadotrophin concentrations with the activity of aromatase enzyme in adipose tissue. No relationship between in-vitro measurements of adipose tissue aromatase activity and FSH or LH levels in serum was found. Four of five women studied with premature ovarian failure had low levels of aromatase activity despite having postmenopausal levels of serum gonadotrophins. In addition, FSH receptors could not be demonstrated on while adipose tissue, isolated fat cells or stromal vascular tissue.

Adipose Tissue↗
PubMed1981

Renin and aldosterone release during sympathetic stimulation in tetraplegia.

1. The effect of endogenous sympathetic stimulation (induced by urinary bladder stimulation) and intravenous infusion of noradrenaline and isoprenaline on blood pressure, heart rate and levels of plasma renin activity and plasma aldosterone were studied in six tetraplegic patients. Data from infusion studies were compared with data from six normal subjects studied in an identical manner. 2. Bladder stimulation in the tetraplegic patients caused a marked rise in blood pressure and fall in heart rate, but no change in plasma renin activity or plasma aldosterone. 3. Noradrenaline infusion resulted in an enchanced pressor response in the tetraplegic patients when compared with the normal subjects. Heart rate fell in both groups. Plasma renin activity and plasma aldosterone did not change in either group. 4. Isoprenaline infusion caused a fall in both systolic and diastolic blood pressure in the tetraplegic patients, unlike the normal subjects in whom there was a rise in systolic and a fall in diastolic blood pressure. Heart rate and plasma renin activity rose in both groups. Plasma aldosterone did not change in either group. 5. We conclude that in tetraplegic patients neither endogenous sympathetic stimulation by bladder stimulation nor infusion of noradrenaline raises plasma renin activity. Isoprenaline increases plasma renin activity to the same extent as in normal subjects. Renin release mechanisms in tetraplegic patients therefore do not appear to be hypersensitive to catecholamines. Plasma aldosterone is not influenced by any of the stimuli.

Adult↗