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Biomedical subjects

R E Oakey

Publications and source records attributed to R E Oakey.

At least 37 records · Page 2Linked to original sources
PubMed1985

Non-protein-bound oestradiol and progesterone in human peripheral plasma before labour and delivery.

Plasma samples were obtained at weekly intervals from the peripheral circulation of 12 women in the last 2-7 weeks of pregnancy. The concentrations of oestradiol and progesterone (isolated by chromatography) were measured by radioimmunoassay; the proportion of each hormone which was not bound to protein was measured by steady-state gel filtration. From these, the apparent concentration of the non-protein-bound form of each hormone was calculated. The mean proportion of oestradiol not bound to protein varied from 0.84 to 2.71% in the different subjects, but within each subject variation was within experimental error. For progesterone, the mean proportion not bound to protein in the different subjects varied from 1.76 to 2.77%; within individuals the proportion remained essentially constant. There was no consistent, recognizable trend as labour approached in the concentration of oestradiol; the concentration of progesterone; the concentrations of non-protein-bound oestradiol or non-protein-bound progesterone; the ratio of the concentrations of progesterone and oestradiol; the ratio of the concentrations of non-protein-bound progesterone and oestradiol. In nine out of 12 subjects, the ratio of the concentration of non-protein-bound progesterone to that of non-protein-bound oestradiol was greater than the corresponding ratio based on total hormone concentrations. These results therefore provide no support for the hypothesis that human labour is preceded by alteration in the progesterone to oestradiol ratio which can be detected by measurement of these hormones in peripheral blood.

Chromatography, Gel↗
PubMed1985

Hydrolysis of deoxycorticosterone-21-yl sulphate and dehydroepiandrosterone sulphate by microsomal preparations of human placentae: evidence for a common enzyme.

The human placenta can hydrolyse both dehydroepiandrosterone-3 beta-yl sulphate (DHASO4-) and deoxycorticosterone-21-yl sulphate (DOCSO4-). There is some uncertainty as to whether the same or different enzymes are responsible for hydrolysis of these substrates. As a fresh approach to this problem we have compared the quantities of DHASO4- and DOCSO4- hydrolysed by microsomal preparations of placentae obtained from 14 normal pregnancies and from 14 pregnancies complicated by steroid sulphatase deficiency. Under the conditions used, and standardizing the results to unit time and quantity of protein, 1380-8830 fmol DHASO4- were hydrolysed by 14 normal placentae whereas less than 1000 fmol DHASO4- were hydrolysed by the other 14 placentae, thereby designated as steroid sulphatase deficient. Net hydrolysis of DOCSO4- by the preparations of normal tissue was 9-52 fmol; hydrolysis of this substrate by steroid sulphatase-deficient tissues was indistinguishable from that by boiled tissue (less than 29 fmol). Thus preparations of placentae which hydrolysed DHASO4- also hydrolysed DOCSO4-; tissues which did not hydrolyse DHASO4- also failed to hydrolyse DOCSO4-. The quantities of DHASO4- and DOCSO4- hydrolysed by the 28 individual placentae showed a positive correlation (r = 0.91, P less than 0.001). The apparent Michaelis constants for hydrolysis of DHASO4- and DOCSO4- were 38 and 274 mumol/l respectively. These results are consistent with the proposal that these substrates are hydrolysed by a common enzyme.

Dehydroepiandrosterone↗
PubMed1984

Cycle initiation in amenorrhoea; the effect of progesterone and oestrogen administration on the pulsatile release of gonadotrophins.

The modulation of pulsatile gonadotrophin release by endogenous ovarian steroids during the normal menstrual cycle may be involved in the initiation of the following menstrual cycle. The absence of this cyclical variation may, in some cases, be the cause of, or contribute to the cause of, amenorrhoea. To assess this the modulatory effect of gonadal steroid administration on the pulsatile release of gonadotrophins was studied in fourteen amenorrhoeic and four oligomenorrhoeic women. Pulsatility was assessed by samples collected at 10 min intervals during a 4 h morning period before and after treatment with either progesterone or micronized oestradiol or a sequential combination of both. Ten patients with intact positive oestrogen-gonadotrophin feedback responded to progesterone treatment by both a significant reduction in LH pulse frequency, from a mean of 4.1 to a mean of 2.1 pulses within the 4 h study period and an increase in pulse amplitude. Progesterone therapy did not affect mean LH concentrations but there was a significant reduction in mean FSH concentrations. In the eight patients with absence of positive feedback, none of the treatment regimes elicited significant changes in LH release. No definable FSH pulses were detected before or after treatment in either group. Both the changes in LH and FSH concentrations and their release observed in this study, support the concept that cycle initiation may be related to a reduced pituitary exposure to LHRH associated with elevated progesterone concentration in the luteal phase of the cycle. This selectively induces FSH synthesis and storage. Release of this stored FSH may occur as a result of failure of the corpus luteum and falling progesterone concentrations.

Adult↗
PubMed1984

Pathological mechanisms in polycystic ovary syndrome: modulation of LH pulsatility by progesterone.

The pulsatile discharge of luteinizing hormone (LH) in nine patients with polycystic ovary syndrome (PCO) and nine patients with amenorrhoea but without PCO, who exhibited LH discharge in response to oestrogen provocation, were studied by 4-h measurement of gonadotrophin pulsatility before and after a course of progesterone injections. No significant differences were found in the gonadotrophin pulsatility patterns of the two groups, although the LH/FSH ratio rose significantly in the patients without PCO after progesterone but not in the patients with PCO, suggesting an abnormality of FSH storage. The ability to discharge gonadotrophins in response to oestrogen provocation has been reported to be present in patients with greater than or equal to 3 LH pulses in a 4-h study period. This, however, was not demonstrated in five of the nine PCO patients despite the presence of 'normal' gonadotrophin pulsatility patterns.

Adult↗
PubMed1984

Antenatal detection of placental steroid sulphatase deficiency: use of a dehydroepiandrosterone sulphate loading test.

Dehydroepiandrosterone sulphate (50 mg) was given intravenously to 15 women in the third trimester of pregnancy in which urinary oestrogen excretion was subnormal (less than 32 mumol/24 h) without recognizable clinical or therapeutic cause. In six patients, this procedure was followed by a marked increase in plasma oestradiol concentrations [mean (SD), nmol/l] before treatment: 44 (13) and 30 min after injection: 279 (31). After delivery, the placentas from all these patients showed steroid sulphatase activity in vitro (greater than 450 units). In the other nine patients, all of whom subsequently showed negligible placental steroid sulphatase activity in vitro (less than 10 units), mean plasma oestradiol concentrations increased only from 18 (9) to 26 (11) nmol/l. Changes in plasma oestradiol concentrations in late pregnancy after injection of dehydroepiandrosterone sulphate therefore readily permit identification of those patients in whom a placental enzyme deficiency is the cause of the subnormal oestrogen production. The defect was identified as steroid sulphatase deficiency by an in-vitro test of placental tissue after delivery.

Dehydroepiandrosterone↗
PubMed1983

Aromatase activity of steroid sulphatase-deficient placentae.

Aromatase activity was measured in homogenates from steroid sulphatase deficient and steroid sulphatase positive placentae. The activity of the aromatase complex was determined from the rate of formation of [14C] oestrone plus [14C] oestradiol when [14C] testosterone was incubated with a rate-limiting quantity of homogenate. A reduced level of aromatase activity was found in vitro in 70% of steroid sulphatase-deficient placentae tested, but the deficiency was much less complete than that of steroid sulphatase. The mean (+/- SD) aromatase activity of steroid sulphatase-deficient placentae was 380 +/- 180 pmol product/h/g tissue (n = 10), significantly lower (P less than 0.001, t-test) than the mean aromatase activity of steroid sulphatase positive placentae (701 +/- 70 pmol product/h/g tissue, n = 10). Seventy per cent of the steroid sulphatase deficient placentae showed lower aromatase activity than that of normal placentae stored for a comparable period of time. Assay imprecision and the sex of the foetus were excluded as reasons for the diminished aromatase activity found. It may arise through an abnormal gene product and consequent alterations in the structure of the microsomal membrane in which both aromatase complex and steroid sulphatase enzymes are retained.

Acetylation↗
PubMed1983

LH pulse frequency in relation to positive oestrogen-gonadotrophin feedback in amenorrhoea.

The relationship between the pattern of pulsatile LH release and the response to oestrogen provocation was studied in twenty amenorrhoeic or oligomenorrhoeic subjects. In 12 subjects with positive oestrogen-gonadotrophin feedback a definite pulsatile pattern of LH release was demonstrated with a pulse frequency of 60--80 min and an increase from nadir to peak ranging between 30 and 58%. The mean basal LH concentration was significantly higher in this group (P less than 0.001). Of eight subjects who had absence of positive feedback, five showed infrequent pulses, 1--2 during the four-hour period. These were of low amplitude and with a percentage increase of 45--70 from nadir to peak. The remaining three did not have a pulsatile pattern of LH release. Positive feedback, as demonstrated by an oestrogen provocation test was thus found only in patient having 3 or more LH pulses in the 4 h study period; an LH pulse frequency similar to that in the early follicular phase in regularly menstruating women.

Adult↗
PubMed1982

The role of antenatal oestrogen in post-partum human lactogenesis: evidence from oestrogen-deficient pregnancies.

Five women with severe ante-partum oestrogen deficiency (in four due to placental steroid sulphatase deficiency and in one due to an unknown cause) had low concentrations of PRL in peripheral plasma at delivery and in the puerperium. These women were unable to establish lactogenesis as assessed from plasma alpha-lactalbumin concentrations on day 4 post-partum. It is concluded that ante-partum oestrogen is required both to ensure adequate PRL secretion and to permit lactogenesis in breast tissue in response to PRL. A review of patients' records in another nine cases of placental steroid sulphatase deficiency indicates that failure to establish breast feeding is a common feature.

Estradiol↗
PubMed1982

Estrogen excretion in pregnant women with leprosy: evidence of diminished fetoplacental function.

Estrogen excretion was assayed in 64 women with leprosy and 15 healthy control women. The mean estrogen excretion was lower in women with leprosy than in controls and the incidence of subnormal estrogen values was higher in the leprosy patients than in the controls. There was an association between infant birth weight and frequency of subnormal estrogen excretion. These features were most marked in women with lepromatous leprosy and are further evidence of diminished fetoplacental function in women with leprosy.

Birth Weight↗
PubMed1981

Stimulation by polypeptides of dehydroepiandrosterone sulphate synthesis in human fetal adrenal slices.

Slices of human fetal adrenal glands (obtained after abortion at 10-18 weeks of gestation) were superfused sequentially with buffer or with buffer incorporating human ACTH, synthetic ACTH (1-24), human GH, human chorionic gonadotrophin, alpha-melanocyte stimulating hormone, metenkephalin, ovine prolactin, beta-lipotrophic hormone or corticotrophin-like intermediate lobe peptide in concentrations from 10(-6) to 10(-9) mol/l. Changes in the concentration of dehydroepiandrosterone sulphate (DHAS) in the effluent in response to addition or removal of the polypeptides were measured by radioimmunoassay. Comparison of the quantity of DHAS in the effluent collected during superfusion (5h) with that present in the tissue initially indicated that synthesis of this conjugated steroid occurred during superfusion. Increases in the concentration of DHAS in the effluent were provoked by exposure of the tissue to all the polypeptides except corticotrophin-like intermediate lobe peptide. These effects were unlikely to be non-specific since incorporation of gonadotrophins, albumin or dextran into the superfusate did not stimulate corticosteroid synthesis from viable bovine adrenal tissue. It was concluded that a number of pituitary polypeptides have the potential to provoke androgen sulphate synthesis by the human fetal gland in early gestation. Consequently there may be no single fetal corticotrophin at this stage and androgen production may be regulated by a number of trophic factors.

Adrenal Glands↗
PubMed1980

Maternal estrogen excretion before perinatal death.

As the value of urinary estrogen measurement in prevention of perinatal death has been questioned, a series of 626 consecutive perinatal deaths was studied to identify possible failures of the technique. 101 deaths related to singleton pregnancies during which urinary estrogen excretion had been measured; 32 deaths were preceded by normal estrogen excretion but no antepartum death from chronic placental failure occurred in this group, whereas 28 of the 69 deaths preceded by abnormal excretion were attributed to this cause. Most of these deaths were for various reasons regarded as unavoidable. There was one death possibly due to induction of labor done because of abnormal estrogen excretion. 4 deaths following abnormal results might have been avoided by appropriate action. 13 deaths might have been prevented if the assays had been performed in cases in which indications were present. It is concluded that urinary estrogen excretion is abnormal before fetal death from chronic placental failure. Other techniques to detect risk of fetal death have not undergone such extensive validation.

Estrogens↗
PubMed1980

The utilization of an estrogen assay system in obstetric practice.

Subsequent to reviewing 626 perinatal deaths in relation to estrogen assay, 1500 consecutive pregnancies were analyzed in detail in regard to utilization of urinary estrogen assays. 2710 assays were performed on 456 cases. The perinatal mortality rate in this high-risk group was 8.8 per 1000 compared with the overall hospital rate of 15.1. Estrogen assays give efficient aid to pregnancy management economically; ways in which their contribution could be improved are suggested.

Cost-Benefit Analysis↗
PubMed1980

Oestrone sulphate in plasma from postmenopausal women and the effects of oestrogen and androgen therapy.

The concentration of oestrone sulphate in peripheral plasma from postmenopausal women was investigated using a method which involved extraction of the conjugate, which was then hydrolysed with acid, and determination (by radioimmunoassay) of the purified oestrone fraction obtained. The concentration of unconjugated oestrone in the same plasma samples was also measured. Postmenopausal women had concentrations of oestrone sulphate in plasma (1.1 +/- 0.36 nmol/l, mean +/- SD, n = 39) similar to those found in women in the follicular phase of the menstrual cycle and less than those found in males (3.2 +/- 0.61 nmol/l, n = 21). The mean ratio of the concentration of oestrone sulphate to that of oestrone in plasma from postmenopausal women (7.9 +/- 3.3) was significantly lower (P less than 0.001, t test) than the mean ratio in men (19.8 +/- 3.8). Treatment with conjugated oestrogens, oestradiol in a cream, oestradiol valerate or ethinyl oestradiol, increased the concentration of oestrone sulphate in the peripheral circulation. In contrast, chronic corticosteroid therapy reduced the level of oestrone sulphate (0.5 +/- 0.11 nmol/l, n = 10) but this was partly restored (to 0.7 +/- 0.13 nmol/l) by concomitant oral dehydroepiandrosterone. Ingestion of piperazine oestrone sulphate (Harmogen, 1.5 mg) by three fasting postmenopausal women was followed 4 h later by oestrone sulphate concentrations five to ten times those found at midcycle.

Adrenal Cortex Hormones↗
PubMed1980

Oestrogen determinations in urine from pregnant women: a review of six years' quality assessment in the United Kingdom.

Since 1974 laboratory performance in the estimation of oestrogens in urine from pregnant women has been assessed in about 150 laboratories by analysis, at intervals of three weeks, of samples of freeze-dried urine. An index of discrimination, delta (= 2.7 SD derived from results reported on six pairs of duplicates), was calculated for each participant laboratory to provide a measure of between-batch precision. There has been a gradual improvement in laboratory performance assessed in this way. Initially, only 45% of the participants were able to discriminate between two 24-hour urine samples, differing in oestrogen by at least 20 mumol, when analyses were performed on different days. In the final period ending March 1980, 61% of participants achieved this standard.

Autoanalysis↗