Five premenopausal women were followed with measurements of androgens, oestrogens, gonadotrophins and sex hormone binding globulin (SHBG) after ovariectomy for benign disease. After a period of 6 weeks without treatment the women were treated with oestradiol 4 mg daily for 8 weeks, oestradiol 4 mg plus norethisterone acetate (NETA) 2 mg daily for 8 weeks and finally oestradiol 4 mg daily for another 8 weeks. The levels of androgens did not change during the various periods. As usual during oral treatment oestrone and oestrone sulphate were elevated while oestradiol levels were in the pre-operative range during treatment, regardless of the addition of NETA. SHBG was elevated during oestrogen-only treatment, while addition of NETA normalized the concentration of SHBG. In the combined NETA period concentrations of free oestradiol and non-SHBG-bound oestradiol were significantly elevated, and gonadotrophins returned to premenopausal levels, in contrast to the high levels in the oestrogen-only periods. Using oral oestrogen therapy it may be preferable to add a progestagen rather than elevate the oestrogen dose. Progestagen will result in more free oestradiol and give greater relief of symptoms, but the potentially harmful effect of progestagens on blood lipids must be considered.

The adrenal and gonadal steroid hormones may continue to regulate lymphoid cells in tissues of mammals throughout their life span. To examine quantitative interrelationships between the endocrine and immune systems, we measured weights of the organs and compared them. The results showed that: (1) The relative weight of the adrenals in adult male hamsters significantly exceeded that of age-matched females. The adult thymus and spleen were heavier in females. (2) Adult gonadectomy induced marked involution of the thymus and adrenal hypertrophy in both sexes. (3) A single oestrone injection at suckling has severe, long lasting effects, with gonadal atrophy and hypertrophy of lymphoid tissues in both sexes for I year. (4) Testosterone in the same way produced adrenal hypertrophy in female hamsters, and adrenal atrophy in males. (5) Thymectomy, at 3 weeks of age, resulted in marked atrophy of the gonads in late adulthood in both sexes. (6) Repeated pulses of cortisone acetate led to marked involution of the thymus and steroid organs, the adrenals and testes. The rather unexpected results, as in (2), (3) and (5), probably represent the ultimate consequence of serial interactions among these organs after treatment. These findings suggest that there is thymus-gonads interdependence even in adulthood, and that subtle counterbalancing co-operation between the adrenals and gonads may regulate lymphocyte functions in tissues. between the adrenals and gonads may regulate lymphocyte functions in tissues.

A case of ovarian arrhenoblastoma in a 14-year-old girl is reported. The patient presented with primary amenorrhea, severe diffuse hirsutism, moderate clitorial enlargement and slight decrease in breast size. Hormonal examinations revealed high plasma testosterone and androstenedione levels, normal plasma prolactin, drhydroepiandrosterone-sulphate, 17-alpha-hydroxyprogesterone, urinary 17 beta oestradiol, oestrone, FSH and LH. Androgen concentrations decreased under dexamethasone suppression test. Following tumor ablation menses occurred spontaneously and normal hormone patterns were observed.

The effect of treatment with the progestogen medroxyprogesterone acetate (MPA) on the peripheral conversion of androstenedione to oestrone and tumour aromatase activity has been examined in post-menopausal women with advanced breast cancer. In addition to being a potent progestational compound, MPA also possesses glucocorticoid properties and glucocorticoids have been shown to stimulate in vitro aromatase activity. While some evidence was obtained of an increase in aromatase activity in tumour tissue after treatment with MPA, peripheral conversion of androstenedione to oestrone was similar when measured before (2.12 +/- 0.67%) and after (1.89 +/- 0.16%) treatment. DNA polymerase alpha activity, measured as a marker of cellular proliferation, decreased from 331 +/- 145 to 156 +/- 93 pmol thymidine triphosphate (TTP)/mg protein per h (P less than 0.02) in tumour samples examined before and after treatment. It is concluded that treatment with high doses of MPA has no effect on the peripheral conversion of androstenedione to oestrone but results in a significant reduction in tumour DNA polymerase alpha activity.

Diurnal changes in the concentrations of oestrone (E1) and oestradiol (E2) in maternal peripheral plasma have been measured in samples of blood taken at one hour intervals from women at 30 to 31, 34 to 35 and 38 to 39 weeks of pregnancy. There was a significant effect of time of sampling on the plasma concentration of E1 at all stages of gestation, and circadian changes in the levels of E1 were apparent at 34 to 35 and 38 to 39 weeks. Peak values were measured around 0830 to 0930 hours, and troughs occurred between 0130 and 0530 hours. Significant effects of time of sampling on the plasma concentration of E2 were found at 34 to 35 and 38 to 39 weeks of pregnancy; night-time concentrations were lower than the peak values at 0730 to 0830 hours. The relation of these changes to the circadian rhythms in the concentrations of cortisol and oestriol in maternal plasma are discussed.

The objectives of the study were to characterise the peripheral plasma oestrone (E1) and oestradiol-17beta (E2) concentrations throughout gestation in the cow and to correlate this with the stage of gestation and fetal number. Cows (n = 10) were equally divided into two groups after non-surgical embryo transfer of in-vitro matured and in-vitro fertilised (IVM - IVF) embryos; Group 1 received a single embryo, Group 2 received twin embryos. Blood was collected about every third day from day 0 (day 0 was defined as first day of standing oestrus), then daily for the last 10 days of gestation and sampling was stopped one day post partum. Plasma E1 concentration exceeded that of E2 throughout gestation in both groups of cows. The time trend concentrations of plasma E1 were significantly affected by the stage of gestation (P < 0.01) and fetal number (P < 0.01) in the last two trimesters of gestation. The time trend concentrations of plasma E2 were significantly affected by the stage of gestation (P<0.01) but not foetal number (P = 0.09). In both groups there was marked preparturient increase in E1 and E2 concentrations. Plasma E2 profile between days 10 prepartum to parturition paralleled E1 in cows carrying a single foetus but was disparate during the same period in the twin-bearing cows. To conclude, our results indicate that although plasma E1 concentration was greater than E2 throughout gestation, both were related to the stage of gestation and that fetal number was correlated with circulating E1 levels in the last two trimesters of gestation.

A cardiodepressant factor (CDF) able to decrease contractile activity of cultured rat heart cells was determined to be located in the lipid-soluble fraction of sera from men in septic shock. This heat-stable CDF has a molecular weight under 1000. Repeated fractionations of sera gave evidence of an oestrone-like chromatographic behaviour. Oestrone, oestradiol and cortisol were immunologically quantified in two groups (recovery and death) of men in septic shock. All of them were elevated in sera from patients with shock. Highest levels of oestrone 4330 pmol 1(-1), (SEM +/- 851, n = 15), oestradiol 1030 pmol 1(-1), (SEM +/- 220, n = 15) and cortisol 1096 pmol 1(-1), (SEM +/- 94, n = 15), were found in patients who failed to recover from shock. However, oestrone levels were the most striking, especially in the male. This study gives evidence for a polarity relationship between the CDF and oestrone, but natural oestrone does not appear to be a direct CDF. Moreover, this study shows that radioimmunoassay of oestrone could be an important index evaluating the severeness of septic shock.

The middle uterine artery of gilts was occluded unilaterally or bilaterally from Days 25 to 70 after mating. The results showed that vascular occlusion of one (N = 7) or both (N = 6) middle uterine arteries during mid-pregnancy markedly reduced, compared with sham-operated controls (N = 7), development of the conceptuses and decreased peripheral oestrogen (oestrone + oestradiol-17 beta) concentrations in maternal blood.

The time course of free oestradiol and oestrone as well as of total (free and conjugated) oestrone was determined in plasma of women after oral ingestion of 3.75 mg conjugated equine oestrogens, or 9.74 micromol of oestrone sulfate, oestrone, and oestradiol, respectively. All these oestrogen preparations led to transiently increased plasma oestrogen levels which fell to normal values after 48 h. The main difference observed between administration of free oestrone or oestradiol and of conjugated oestrogens (oestrone sulfate or equine oestrogens) was a much more protracted influx of oestrogens from the intestine into the plasma compartment, with a tendency to more sustained plasma levels, if conjugated oestrogens were administered. There was a consistent discontinuity in plasma oestrogen levels 10--12 h after oral ingestion of all the preparations examined indicating enterohepatic circulation. Comparison of "areas under the curve" obtained with the present preparations to similar previous studies on ethinyl oestradiol indicated that the bioavailability of the non-ethinyl oestrogens is by more than one order of magnitude less than that of ethinyl oestradiol after oral administration. The ratio of oestrone/oestradiol was the highest with free oestrone and similar among the other three preparations indicating an increased metabolism of sulfoconjugated oestrone to oestradiol after oral application when compared with free oestrone.

Oestrogen treatment of climacteric disorders, chiefly with formulations based on oestradiol or oestrone, which cause much less metabolic disturbance than synthetic oestrogens, is now widely accepted. Physiological replacement requires a blood production rate approaching 0.5 mg/day. Deleterious effects of oestrogen loss are known, but the appropriate scale of long-term prophylaxis with oestrogens is controversial. Evidence for a risk of endometrial carcinoma from unopposed oestrogen therapy is inconclusive but has focused attention on the concurrent use of progestogens, which is rising rapidly but is at present no more than 10%.

Conjugated equine oestrogens (0.625 mg) were administered daily and intravaginally to 7 postmenopausal women (aged 70-93 yr) for 14 days. Blood samples were taken at days 1 and 14 immediately before and 2, 4 and 6 h after oestrogen application and at days 4, 6, 8, 11 and 13, 4 h after application. Serum samples were analyzed with respect to total oestrone (E1), unconjugated 17 beta-oestradiol (E2), FSH and LH. Serum total E1 and E2 increased rapidly at day 1 to luteal and follicular phase levels respectively. After that total E1 levels decreased to a plateau corresponding to follicular phase values and remained at that level throughout the treatment period. Serum E2 remained at the follicular phase level during the entire period of treatment. No increase in serum oestrogens could be detected after oestrogen application at day 14. Serum gonadotrophins were already suppressed at day 4 and further decreased to premenopausal values during the latter half of the treatment period. It is speculated that the effects of oestrogens upon a post-menopausal vaginal mucosa involves a diminished resorption of conjugated oestrogens. This effect is, however, not sufficient to avoid systemic effects at the dosage used.

In vitro incubation of pituitary, hypothalamus and cerebral cortex with [3H]oestrogens revealed that the oestrogens are actively metabolized by these tissues. The covalent binding of oestrone and oestradiol to acid precipitable proteins was observed. Pituitary from male rats exhibited higher covalent binding of oestrogens than females. The 2-hydroxylation was found to be greater than 16-hydroxylation. Furthermore, male pituitary exhibited higher 2-hydroxylation of oestrogens than females. No such sexual dimorphism was observed in 16-hydroxylation. C17-reduction was found to be greater than oxidation in these tissues. Furthermore, the C17-reduction in pituitary and hypothalamus from females was greater than males, which is in contradistinction to protein binding and 2-hydroxylation of oestrogens. In both male and female animals the pituitary was metabolically more active than hypothalamus and cortex. In addition, oestradiol was hydroxylated more than oestrone either at 2- or 16-positions. These results indicate that in central nervous system and pituitary the oestrogens are metabolized preferentially by 2-hydroxylation pathway and it is suggested that the in situ metabolism of oestrogens in neuroendocrine tissues may be important in the control of oestrogen effects on neuroendocrine function and sex behaviour.

Competitive protein binding studies, using oestrone as the inhibitor, demonstrated that mouse amniotic fluid contains a high affinity oestradiol-binding component precipitable by monospecific rabbit anti-alpha-foetoprotein (AFP) in a double-antibody radio-immunoassay. On disc gel radio-electrophoresis the oestrogen-binding entity migrated as an alpha-1 protein which was immunoreactive to anti-AFP serum. Immunoprecipitation of protein-bound [3H]-oestradiol from solution was proportional to anti-AFP immunoglobulin G concentration. Rabbit antisera directed against other major proteins in amniotic fluid did not produce significant precipitation of radioactivity. Only when anti-AFP antiserum was the complexing protein and AFP, either crude or purified, was the binding protein did a substantial [3H]-oestradiol precipitate form. Our data suggest that oestradiol and anti-AFP do not bind at the same sites on the AFP molecule and that estradiol does not serve as a hapten in the production of anti-AFP serum in rabbits.

Prolactin, oestrone, oestradiol, FSH and LH concentrations have been determined in postmenopausal women receiving different forms of hormone replacement therapy. While the serum oestrogen levels achieved were sufficient to cause a significant decrease in circulating FSH and LH levels, no significant change in prolactin concentrations was found. Two other findings are of interest: despite the absolute concentrations achieved, the ratio of FSH to LH and the ratio of oestradiol to oestrone did not change significantly on any of the hormone formulations used; and while FSH and LH were both suppressed to a significant degree on therapy neither was suppressed to premenopausal values suggesting the possibility of a 'female inhibin' in the normal regulation of gonadotrophin secretion.

Urine collections (24 hr) were made at weekly intervals from four Pony mares from the 3rd or 4th month of pregnancy until parturition. Separation of oestrogens on Celite columns was followed by Kober measurements of oestrone and equilin. Individual differences were noted in peak amounts of total oestrogens excreted (200 to 800 mg/day), when oestrone constituted 80 to 95% at the 6th to 7th months. Although equilin increased in later gestation, oestrone remained the major product. Total oestrogen values decreased rapidly from the peak and then more gradually towards the end of pregnancy. During the last 3 weeks the decline in the ratio of oestrone to equilin was reversed in all mares.

Concentrations of oestrogens in the blood plasma and seminal plasma of mature boars are high. However, little is known about their concentrations after reaching sexual maturity. The aim of this study was to determine the concentration of oestrogens in blood plasma and seminal plasma of boars during the postpuberal period. Free and conjugated oestrone and oestradiol-17beta were determined by radioimmunoassay in blood from the testicular vein and artery, and peripheral circulation as well as in seminal plasma collected from 18 Polish Landrace boars. The animals were divided into three groups (n = 6) according to age (8, 12 and 16 months, respectively). Oestrone was predominant free and conjugated oestrogen. The highest values of oestrogens were measured in the testicular vein (p < or = 0.05). The concentrations of oestrogens in seminal plasma did not differ from those found in the peripheral circulation. An age-dependent increase in levels of all four oestrogens (p < or = 0.05) was observed. This can be associated with biochemical maturation of the reproductive system during the postpuberal period.

Plasma levels of total oestrogens and dehydroepiandrosterone (DHA) were measured by radioimmunossay in samples taken from various blood vessels in both maternal and fetal compartments in 11 Pony mates. High concentrations of oestrogens (greater than 100 ng/ml of plasma), expressed as oestrone equivalents, were found in the fetal circulation. On both the fetal and maternal sides, oestrogen concentrations were lower in blood going to than from the placenta. DHA concentrations, on the other hand, were higher in blood flowing to the placenta from the fetus. The fetal gonads were seen as the source of DHA, which was present in remarkably high concentrations (greater than 800 ng/ml of plasma) in venous samples from fetal ovaries and fetal testes. A precursor role in placental oestrogen formation is suggested for DHA secretion by the fetal gonads.

Adsorption of hydrophobic contaminants at the particle/water interface is one of the key processes controlling their fate in the aquatic environment. The sorption of the natural female hormones oestrone and 17 beta-oestradiol has been studied under simulated riverine conditions. Both the kinetics and the effects of varying fundamental environmental parameters (e.g. sediment properties) on the thermodynamic equilibrium partition coefficient (Kp) have been studied in continuous and batch sorption experiments, respectively. Results showed that the sorption of oestrone and 17 beta-oestradiol by sediment was relatively slow, reaching equilibrium in 50 days. In addition, relatively small adsorption of both oestrone and 17 beta-oestradiol onto the sediment was observed, with Kp values between 200 and 250 mL g-1. The comparable Kp values of the two compounds reflect their structural similarity. It can be concluded that the two endocrine disruptors, oestrone and 17 beta-oestradiol remain primarily in association with the aqueous phase.

A heterohybridoma was produced by the fusion of sensitized peripheral blood lymphocytes (PBLs) with a previously derived heteromyeloma, generated by the fusion of bovine PBLs with murine myeloma cells. The sensitized bovine PBLs were collected from a steer immunized with an oestradiol-ovalbumin conjugate. The cell lines resulting from the fusion were screened for the production of bovine antibodies to oestradiol. A stable heterohybridoma was isolated which secreted a bovine IgG1 to oestrone/oestradiol. The use of sensitized PBLs together with heteromyeloma fusion partners has proved to be a reliable and simple way of producing monoclonal antibodies against specific haptens.

Oestrogen was measured in urine samples collected from captive females representing 7 species of New World monkey to provide an overview of the applicability of such formation in the noninvasive monitoring of ovarian function and to assess the potential applicability of such information in phylogenetic studies. Species available for study were the pygmy marmoset, common marmoset, red-bellied tamarin, cotton-top tamarin, golden lion tamarin, Goeldi's monkey and the owl monkey. Oestrone conjugates were measured in serially collected urine samples to demonstrate ovarian cyclicity. Urine samples obtained during the luteal phase were subjected to HPLC to identify immunoreactive oestrogens; oestrone and oestradiol-17 beta accounted for almost all of the immunoreactive oestrogen detected while oestriol content was negligible. Urine samples obtained during the follicular phase and luteal phase were subjected to glucuronidase hydrolysis, sulphatase hydrolysis and acid solvolysis, which revealed that the major immunoreactive oestrogen metabolite was: (1) oestradiol sulphate in the pygmy marmoset and common marmoset, (2) residual oestradiol in the red-bellied tamarin, (3) residual oestradiol and oestrone glucuronide in the cotton-top tamarin, and (4) oestrone glucuronide in the golden lion tamarin, Goeldi's monkey and owl monkey. A phylogenetic tree based on the above shifts in oestrogen excretion suggested that clawed New World monkeys are specialized and that the lineages leading to the study species split off in the following order: Goeldi's monkey, golden lion tamarin, cotton-top tamarin, red-bellied tamarin, common marmoset and pygmy marmoset.