Plasma Estrone Research Articles

Plasma hormone levels in beef heifers during prostaglandin-induced parturition

Plasma hormone levels were determined at frequent intervals in 12 two-year-old Hereford heifers after treatment with prostaglandin F2α on day 267 of gestation to induce parturition. Of the 12 animals, six also received a daily injection of estradiol-17β until calving occurred. An additional six heifers received no treatment and therefore served as a control group. The treatment with PGF2α was effective since the treated heifers calved a mean of 12 days sooner than the untreated heifers (P < .01). A metabolite of PGF2α, 13, 14-dihydro-15-keto PGF2α, rose to a peak level in the plasma within one hour after injection (im) of PGF2α then declined to a baseline level within four hours. The plasma progesterone level had fallen significantly within two hours after injection, but no change in plasma estradiol-17β or estrone was observed. In the eight heifers that responded, plasma estrogen levels were greater at the time of treatment than in the four heifers that did not respond.

Plasma concentrations of steroid hormones in sows infected experimentally with Leptospira pomona or porcine enterovirus strain T1 in late gestation

Plasma levels of progesterone, corticosteroids and oestrone were determined during the late stages of pregnancy in four sows experimentally infected with Leptospira pomona and in a group of three sows in which fetuses were inoculated in utero with a strain of porcine enterovirus. Only one of the seven infected sows farrowed at full term. All fetuses were dead and delivery was prolonged in litters infected with the virus. In the sows with leptospirosis almost all piglets were expelled dead or in a weak condition. The amounts of progesterone in plasma were within the normal range and showed a decrease shortly before abortion similar to that observed before parturition in normal animals. The elevation in plasma corticosteroids at normal parturtion was not seen at abortion. An irregular pattern with rising levels of plasma oestrone was found in most sows. Peak levels of oestrone were usually reached close to the time of delivery, but occured earlier in most sows which aborted well before term. In conclusion differences were noted between the endocrine patterns in normal parturition and in abortion caused by infectious agents in sows.

A Radioimmunological Method for Oestrone

A specific antiserum to oestrone has been used to develop a radioimmunoassay. No chromatographic separation step was included. A small amount of plasma (0.01--0.15 ml) was extracted once with diethyl ehter. The method was used to estimate plasma levels of non-conjugated oestrone in women during uncomplicated late pregnancy. The oestrone plasma concentrations showed a gradual increase from a mean of 4 ng/ml in the 22nd week to 11 ng/ml in the 41st week. Great individual variations were found. No systematic changes of unconjugated oestrone plasma concentrations were noticed during a 24-hour period in late pregnancy. Short term studies revealed that large and rapid fluctuations may appear in the levels of unconjugated oestrone during pregnancy.

Preparturient changes in plasma concentrations of estrone, estradiol-17β and estradiol-17α in the fetal calf: Effects of dexamethasone infusion

The concentrations of total estrogens in fetal calf plasma were determined during a 6–10 day period immediately before delivery. Comparison was made between levels found in untreated calves and calves infused with dexamethasone at the rate of 0.1, 1.0 and 10 mg/24 hours. In untreated calves the plasma estrone, estradiol-17β and estradiol-17α levels remained relatively constant at 38 ± 7 ng ml −1 (mean ± SEM n = 3), 46 ± 6 ng ml −1 and 29 ± 5 ng ml −1 respectively. Infusion with dexamethasone at 0.1 mg/24 hr (3 calves) and 1.0 mg/24 hr (3 calves) was without dramatic effect on plasma estrogen levels. However, in one fetus infused with 10.0 mg/24 hr the dexamethasone treatment may have caused a transitory rise in the levels of all estrogens examined.

Breast cancer in Britain and Japan: Plasma oestradiol-17β, oestrone and progesterone, and their urinary metabolites in normal British and Japanese women

The plasma concentrations of oestrone, oestradiol- 17β and progesterone, and the urinary excretion of oestrone, oestradiol- 17β, oestriol and pregnanediol have been determined in normal Japanese and British adolescent, pre-menopausal, menopausal and post-menopausal women. The amounts of plasma oestrogen in British and Japanese women were not significantly different except in the adolescent group. In this latter category the mean level of plasma oestrone and oestradiol- 17β in the luteal phase was significantly higher in Japanese compared with British women. The mean excretion of urinary oestrogens in the two races was similar for all age groups studied, as was plasma progesterone and urinary pregnanediol. The mean ratio of oestriol to oestrone and oestradiol- 17β for Japanese was higher than that for British women in the two pre-menopausal groups, although the difference was not statistically significant. The difference in the incidence rates of breast cancer in Britain and Japan does not appear to be related to differences in plasma levels of oestrogens or progesterone.

Estrone and Estradiol in Patients with Cirrhosis of the Liver: Effects of ACTH and Dexamethasone1

To study the influence of the adrenal gland on plasma estrogen levels in male patients with hepatic cirrhosis, estrone and estradiol were measured under a variety of experimental conditions. Compared to controls, estradiol levels were moderately elevated by 26% (P is less than 0.05) in patients with hepatic cirrhosis (28.5 +/- 5.4 vs. 36.0 +/- 4.7 pg/ml plasma; n: 12), whereas estrone levels exhibited a two- to threefold increase under basal conditions (32.5 +/- 5.6 vs. 67.8 +/- 20.8 pg/ml; P is less than 0.01). ACTH application resulted in a striking increase in plasma estrone levels in both patients with hepatic cirrhosis and in normal subjects (61.8 +/- 27.5 vs. 27.3 +/- 7.8 pg/ml). During stimulation with ACTH, estradiol levels showed no significant changes. After suppression of the adrenal gland by dexamethasone administered for 5 days, plasma concentrations of estrone and estradiol were found to be reduced. The absolute decrease of estrone was significantly greater in patients with hepatic cirrhosis than in healthy male subjects (35.5 +/- 12.6 vs. 21.3 +/- 6.0 pg/ml; P is less than 0.05; n: 8). Estrogen values, however, were still high in patients with hepatic cirrhosis after 5 days of dexamethasone administration (37.1 +/- 17.6 pg estrone/ml and 23.9 +/- 3.6 pg estradiol/ml plasma). It is suggested that elevated plasma values of estrogens in this disorder may be derived predominantly from adrenal production. Peripheral conversion of androgens to estrone rather than to estradiol appears to be more effective in sustaining plasma levels of estrogens in patients with hepatic cirrhosis.

Hormonal changes associated with experimentally produced cystic ovaries in the cow.

Cystic ovaries were experimentally produced by i.m. injection of 5 mg oestradiol valerate on Day 16 of the oestrous cycle or by s.c. injection of 100 ml antiserum to bovine LH before the onset of oestrus. The length of the cycle after both treatments was altered. The cysts formed after oestradiol injection were relatively small (2-5-3 cm diameter) and thin-walled, and were accompanied by relatively low plasma oestrone and high oestradiol levels; those after LH antiserum treatment were large (5-0-6-0 cm) and firm and associated with relatively low oestradiol and high oestrone levels. The results of the hormone assays after treatment support the theory that cystic ovaries could result from premature LH release or an insufficiency of LH at the time of ovulation.

Placental metabolism of dehydroepiandrosterone sulphate in normal pregnancy.

An intravenous injection of 50 mg dehydroepiandrosterone was given to 19 women at the 38th week of pregnancy. The concentration of androstenedione, testosterone, oestradiol and oestrone in plasma was measured at intervals following the injection. The concentration of androstenedione and testosterone rose rapidly; reaching a peak after 10 minutes and returning to near baseline level by 30 minutes. Oestradiol rose more slowly, reaching a peak after 45 minutes and being sustained at high levels for 3 1/2 hours before returning slowly to baseline. Oestrone rose yet more slowly and did not reach a peak until 2 1/2 hours after the injection. It is concluded that the steroid responses are too variable from one individual to another for this test to be useful in the clinical assessment of fetal wellbeing but that it was likely to be a powerful tool in the investigation of placental steroid biogenesis.

Further studies on sex hormones in male homosexuals.

Plasma estrone, dihydrotestosterone, luteinizing hormone (LH), and percentage-free testosterone levels were determined in 26 predominantly or exclusively homosexual males (20 to 33 years of age) and in an age-matched control group. Although the homosexual and control groups showed a broad overlapping for all hormonal factors measured, highly significant differences between the groups were found without exception. The medians of the homosexual group (control group) and the significance levels for the two-sample rank tests were as follows: estrone 3.07 (2.43) ng/100 ml, P less than .01; dihydrotestosterone 66.0 (49.2) ng/100 ml, P less than .01; percentage-free testosterone 10.7% (9.7%), P less than .02; LH 35.1 (24.9) ng/ml, P less than .001. These findings can in part be explained by the higher LH secretion in the homosexual subjects.

Effects of Indomethacin on Corpus Luteum Function and Pregnancy in Rhesus Monkeys

Indomethacin was administered during the luteal phase of the menstrual cycle and during late pregnancy in rhesus monkeys. The plasma indomethacin concentrations achieved were within the ranges effective in inhibiting the microsomal prostaglandin synthetase, even when allowances were made for 90% binding to plasma proteins. There were no significant differences in duration of the luteal phase of menses or in luteal phase progesterone concentrations with indomethacin treatment. Our findings do not support the hypothesis that endogenous prostaglandins are important luteolysins in primates. They provide indirect evidence that administration of prostaglandin synthetase inhibitors would have no therapeutic benefit in treatment of the "short luteal phase" syndrome in women. Indomethacin administration in late pregnancy had a significant effect in prolonging gestation. Uteri of treated animals remained flaccid and distended after fundal hysterotomy and removal of fetuses. Maternal plasma concentrations of unconjugated estradiol, estrone, and progesterone during indomethacin treatment were within the expected ranges for late pregnancy in rhesus monkey, although in two animals we found transient, unexplained, high concentrations of estrone in maternal plasma. Chronic indomethacin administration was associated with continuing fetal and placental growth, a 50% fetal mortality rate, oligohydramnios, and meconium staining, and maternal anemia but normal bleeding times. Severe oligohydramnios was noted in preterm as well as post-term fetuses, indicating that indomethacin per se alters regulation of amniotic fluid volume.

RADIOIMMUNOASSAY OF OESTRONE IN PLASMA

A radioimmunoassay (RIA) for oestrone (Oe1) in plasma was developed using an ether extraction, a partition between NaOH and light petroleum, and a TLC as sample purification and an antiserum cross-reacting with Oe2 for the final assay (Method A1). The reliability criteria are given in detail. In order to simplify this method a highly specific antiserum was developed by using Oe1-3-hemisuccinate-BSA as an antigen. Using this antiserum for the final assay but omitting the TLC (Method B) the Oe1 concentration in male plasma was 76% overestimated (Method B compared with Method A1). In pregnancy plasma Oe1 could specifically be determined after a simple ether extraction (Method C). It was concluded that the use of a highly specific antiserum (as determined by cross-reaction studies) for the final assay does not necessarily imply that a chromatographic sample purification can be omitted without loss in assay specificity. This appears to be true mainly in cases where the steroid concentration of the sample is low. Normal values of Oe1 from 80 healthy adult males were ascertained by Method A1. Age group I (22-61 years, n = 48) ranged from 1.22-5.60 ng/100 ml, median 2.81; age group II (67-90 years, n = 32) from 1.55-6.40, 100 median 3.41. The small increase of Oe1 with age was highly significant.

Oestrone, oestradiol and testosterone in normal and hypogonadal men following LH-RH or HCG stimulation.

oestrone, oestradiol-17beta and testosterone in serum were measured during a LH-RH infusion test and a Leydig cell function test with HCG in healthy men and in patients with primary or secondary hypogonadism. Following infusion of LH-RH increases of LH (+112%), oestradiol (+62%) and testosterone (+51%) were observed in normal men, while oestrone remained unchanged. Of the patients only those with Klinefelter's syndrome showed a significant increase in testosterone and oestradiol after LH-RH infusion. During the Leydig cell function test oestradiol and testosterone exhibited a largely parallel pattern under normal and pathological conditions as well as in subjects with experimental hypogonadism. Augmentations of plasma oestrone were usually smaller than those for oestradiol.

A Testosterone-Secreting, Gonadotropin-Responsive Pure Thecoma and Polycystic Ovarian Disease

A 31-yr-old hirsute female with oligoamenorrhea since menarche had markedly elevated peripheral plasma testosterone (T) concentrations of 250-255 ng/100 ml (normal 20-60 ng/100 ml), which lacked a diurnal rhythm, were not suppressed by dexamethasone, were decreased by ACTH, and were massively increased to 2,530 ng/100 ml by human chorionic gonadotropin (hCG). The binding capacity of T-binding globulin (TeBG) was 0.2 mug/100 ml (normal = 1.1-3.3 mug/100 ml). Plasma delta 4-androstenedione (A) was elevated at 374-681 ng/100 ml (normal = 90-135 ng/100 ml). Plasma estrone (E1) and estradiol (E2) were normal. The endometrium was proliferative. A T-secreting tumor was suspected because the plasma T levels were higher than those observed in polycystic ovarian disease. Exploratory surgery revealed bilateral polycystic ovaries and a pure thecoma in the right ovary which was not visible on surface examination. The thecoma did not contain granulosa cells. Plasma T in the right ovarian vein, draining the tumor, was 28,200 ng/100 ml and in the left ovarian vein was 2,600 ng/100 ml. Plasma A was elevated in both ovarian veins: 11,170 ng/100 ml on the left and 8,360 ng/100 ml on the right. The thecoma contained 1.35 mug/g of T and only 0.014 mug/g and 0.007 mug/g of E2 and E1, respectively. Plasma A and T after bilateral oophorectomy and removal of the thecoma were normal at 184 ng/100 ml and 40 ng/100 ml, respectively. 1) This pure thecoma produced primarily T rather than E1 OR E2 and was gonadotropin-responsive. 2) A very high plasma androgen level in a female is an important clue to the presence of a tumor. A T-secreting tumor should be ssupected when the peripheral plasma T is over 250 ng/100 ml and when plasma T increases to over 1,000 ng/100 ml following hCG stimulation. 3) Tumors cannot be classified as estrogenic or androgenic on the basis of the character of the endometrium.

Plasma estrone, prolactin, neurophysin, and sex steroid-binding globulin in chronic alcoholic men

The feminization frequently observed in men with alcoholic liver disease has not been satisfactorily explained by existing reports. We have measured plasma estrone, prolactin, estrogen-stimulated neuorphysin, and sex steroid-binding globulin concentrations in 50 men with chronic alcoholism and varying degrees of alcoholic liver disease in an effort to further elucidate possible hormonal mechanisms responsible for the observed feminization. Plasma concentrations of each of these parameters were at least two-fold elevated ( p ⪕ 0.01) when compared to values obtained for the same steroid or protein in plasma obtained from normal men. The plasma concentrations of estrone and prolactin in men studied with gynecomastia were significantly greater ( p ⪕ 0.01 and p ⪕ 0.05 , respectively) than were the concentrations of these two hormones in those without this physical sign. Similarly, those men with spider angiomata had significantly greater ( p ⪕ 0.01) plasma estrone levels than did the men without this cutaneous vascular abnormality. These significant hormone elevations may contribute to the pathogenesis of feminization so frequently observed in chronic alcoholic men.

Foetal plasma steroid concentrations related to gestational age and method of delivery

Levels of total corticosteroids and unconjugated oestrone and oestradiol-17β in human umbilical arterial and venous plasma at the time of delivery were measured, using competitive protein-binding methods. Increased corticosteroid levels were associated with the establishment of labour and, following delivery at term (38–40 weeks), corticosteroid levels were least when the mother was not in labour and greatest when the mother was in established spontaneous labour at the time of delivery. A surge and peak in corticosteroid levels was observed at 35–37 weeks of gestation in infants delivered by elective Caesarean section and per vaginam following spontaneous labour and thus was not related to labour. Oestrone and oestradiol-17β levels in umbilical venous plasma have also been shown to change with the establishment of labour, oestrone levels increasing and oestradiol-17β levels falling, so that oestrone predominates. Following spontaneous labour with vaginal delivery, there was a significant effect of parity upon oestrogen levels, higher levels of both oestrone and oestradiol-17β occurring in infants from primiparous mothers. This effect of parity was not observed following Caesarean section, either when in early labour or not in labour. It is concluded that fluctuations in corticosteroid and oestrogen levels in the feto-placental circulation are associated with the establishment of labour and may therefore have a regulatory role in human parturition.

AGE DEPENDENCE OF PLASMA OESTROGEN RESPONSE TO HCG AND ACTH IN MEN

Twelve men, 19-40 years old, and 12 men, 60-86 years old, were given ACTH and in a second test series, HCG. Oestrone, oestradiol-17beta and cortisol were measured in the plasma before and after stimulation. Under basal conditions oestrone and oestradiol as well as the percentage binding of testosterone increased significantly with age, whereas cortisol remained unchanged. The administration of HCG resulted in higher levels of both plasma oestrone and oestradiol in older subjects than in younger ones, although the percentage increase was smaller. ACTH stimulation leads to higher levels of oestrone in the older group, whereas oestradiol remained unchanged. Cortisol rose 3.5 fold in both groups. Regarding absolute concentrations of oestrone and oestradiol the ability of the adrenals and of the testes to respond to exogenous gonadotrophin and adrenocorticotrophin appeared to be preserved despite ageing, though the relative responses of oestrone and oestradiol after HCG and of oestrone after ACTH were decreased in old as compared to young men.

Indices of gonadal function in the human male. I. Plasma levels of unconjugated steroids and gonadotrophins under normal and pathological conditions.

A radioimmunoassay technique for the simultaneous measurement of eight unconjugated steroids (progesterone, pregnenolone, dehydroepiandrosterone, androstenedione, testosterone, dihydrotestosterone, oestrone and oestradiol) in the peripheral plasma of human males is described. Determinations of these steroids and of immunoreactive FSH and LH were carried out on the plasma of twenty-one normal individuals and the levels were compared to those of eleven and ten males exhibiting oligospermia and azoospermia, respectively. Mean values and tolerance limits for each hormone, based on a lognormal distribution of individual values, are presented for all groups. Oligospermia was associated with a significant reduction in plasma dihydrotestosterone and testosterone levels. Azoospermic subjects also exhibited decreased dihydrotestosterone levels but a normal range of testosterone concentrations. Mean peripheral plasma levels of FSH were significantly elevated in both pathological groups and this was paralleled in the azoospermic men by increased concentrations of plasma LH.

Indices of gonadal function in the human male. II. Seminal plasma levels of steroids in normal and pathological conditions.

A radioimmunoassay method developed previously for the measurement of unconjugated pregnenolone, dehydroepiandrosterone, androstenedione, testosterone, dihydrotestosterone and oestradiol in peripheral plasma was applied to the assay of these steroids in seminal plasma of normal, oligospermic and azoospermic males. It was not possible to use the plasma assay method for the determination of progesterone and oestrone in seminal plasma, because some of the reliability criteria were not fulfilled. A detailed analysis of these steroids in the peripheral plasma of the same subjects has been described previously. The levels of all steroids in seminal plasma were significantly lower than the corresponding blood levels. The ratios of blood plasma/seminal plasma levels of the various steroids varied from 37 (testosterone) to 1.7 (dihydrotestosterone). There was a positive correlation between the testosterone and dihydrotestosterone levels of the seminal plasma of normal and azoospermic subjects. The concentrations of dihydrotestosterone, pregnenolone and oestradiol were significantly lower in azoospermic subjects than in normals. The only pathological finding in the seminal plasma of oligospermic subjects was a diminished level of dihydrotestosterone. Enzymic hydrolysis of a seminal plasma pool resulted in a 3- to 8-fold increase in the concentration of pregnenolone, dehydroepiandrosterone, testosterone, dihydrotestosterone and oestradiol, indicating that human seminal plasma contains large amounts of steroid conjugates. It is suggested that the analysis of steroids in the seminal plasma in combination with determinations in peripheral plasma may be a valuable aid to the assessment of testicular function.

Hormonal control of delayed development in Macrotus waterhousii. II. Radioimmunoassay of plasma estrone and estradiol 17-β during pregnancy

The leaf-nosed bat is thought to exemplify the process of delayed development. Copulation occurs in late September through early October with an ensuing, uninterrupted gestation lasting until the following spring. Maternal plasma concentration of estrone ( E 1) and estradiol 17-β ( E 2) were measured at regular intervals in the 9-mo gestation period. A pattern was found consisting of relatively high concentrations ( E 1 = 15 pg/ml; E 2 = 60 pg/ml) during the first trimester while the following 5 mo of retarded development was characterized by much lower estrogen concentrations ( E 1 = 11 pg/ml; E 2 = 35 pg/ml). The last few weeks of pregnancy displayed drastic increases in hormone levels ( E 1 = 25 pg/ml; E 2 = 78 pg/ml). Our data lend support to a possible hormonal regulation of delayed development. The first estrogen peak is thought to correspond to the time of nidation or to the period shortly thereafter, the decreased estrogen levels occur during the period of embryonic diapause and the final estrogen peak corresponds to the culmination of fetal development and growth and parturition.

Determination of Conjugated and Free Estrogen in Male Plasma

Radioimmunoassay for conjugated and free estrone (E1), estradiol-17beta(E2) and estriol (E3) in male plasma was investigated, while no precise determination of conjugated estrogen in male plasma had been established. Each tritiated estrogen glucuronides for determining the recovery was added to 3 ml of plasma samples. These plasma samples were extracted with acetone, hydrolyzed with 15 vol% HCl at 100 degrees C for 60 minutes, and resulting free estrogens were extracted with ether. These extracts were washed with 1% NaOH and 1% NaHCO3, and applied to microcolumn of Sephadex LH-20. Then they were determined by the radioimmunoassay as the same method of evaluation for free estrogen. Each mean values of plasma free and conjugated estrogen in 10 normal adult males was as follows: 36.0 +/- 9.81 pg/ml(free E1), 29.5 +/- 11.0 pg/ml(free E2), 1.80 +/- 1.27 pg/ml (free E3), 31.0 +/- 12.6 pg/ml (conjugated E1), 36.0 +/- 14.2 pg/ml (conjugated E2), 30.6 +/- 8.35 pg/ml (conjugated E3). Conjugated estrogen to free estrogen ratio was 1.45.