Total Unconjugated Oestrogens Research Articles

Investigations on hormonal changes around parturition in the dog and the occurrence of pregnancy-specific non conjugated oestrogens.

Concentrations of progesterone and estradiol-17 beta were determined throughout pregnancy in 6 to 10 bitches (exp. 1); in experiment 2 peripartal changes of estradiol-17 beta, estrone, progesterone, cortisol, prolactin and growth hormone were determined in 5 bitches; in experiment 3 total unconjugated oestrogens were determined by radioimmunoassay and radioreceptorassay in placental tissue from 25, 53, 60 and 64 days pregnant bitches. No pregnancy specific increase of estradiol-17 beta could be observed; estradiol-17 beta levels decreased prior to parturition concomitant with the decrease of progesterone, suggesting a likewise luteal origin of estradiol-17 beta in the pregnant and non pregnant dog. Cortisol and growth hormone concentrations were elevated at the time of parturition, prolactin concentrations remained unchanged but were higher in pregnant than in non pregnant dogs. No hints in respect to a specific placental oestrogen production were obtained when examining placental tissue. The hypothesis is put forward that the high sensitivity of the haematopoietic system of the dog to oestrogen was an important factor in respect to evolution of endocrine control of pregnancy and parturition in this species which-in respect to placental oestrogen production-seems to be different from most other domestic animal species.

Oestrogens in Faeces as an Indicator of the Foeto-Placental Unit Function in Mares

Total of 30 pregnant mares were used in this study: 17 Thoroughbred and 13 Primitive Polish Horse. The concentration of total unconjugated oestrogens was determined by radioimmunoassay in faecal samples obtained every second week after mating until delivery or interruption of pregnancy. Concentration of oestrogens in pregnant healthy mares ranged from 40 to 200 ng/g and showed typical profiles for pregnancy. In 5 of 30 mares (16.6%) of either breed abortions and cases of embryonic death occurred. Abortions were preceded by sharp or gradual decrease in oestrogen concentration, whereas prior to embryonic death no elevation of the level of these hormones was noted. The present data suggest that determination of faecal oestrogens may serve as an indicator of the foeto-placental unit function during either the physiological or pathological pregnancy.

Peripheral blood concentrations of plasma steroids and a metabolite of prostaglandin F 2α in pregnant cows vaccinated against foot and mouth disease

Blood samples were collected from 82 pregnant cows at 6-h intervals to determine the effects of vaccination against foot and mouth disease (FMD) on plasma concentrations of progesterone, total unconjugated oestrogens, total corticosteroids and 13,14-dihydro-15-keto-prostaglandin F2 alpha (PGFM). Twenty-two (26.8%) cows showed a strong post-vaccinal reaction in the form of a significant (P < 0.05) elevation in rectal temperature, accompanied by significant (P < 0.01) increases in plasma progesterone and corticosteroid concentrations for 36-42 h after vaccination. Seven (8.5%) cows returned to oestrus within 5-6 days when vaccinated during the first month of pregnancy and nine (10.9%) gave birth prematurely within 72-80 h when vaccinated during the last month of gestation. The importance of post-vaccinal reactions on embryonic mortality and premature birth is emphasized. It is suggested that cows in early and late pregnancy are most susceptible to adverse effects of vaccination against FMD.

Progesterone, oestrogens and selected biochemical constituents in plasma and uterine flushings of normal and repeat-breeder buffalo cows

SUMMARYSixty-four lactating buffalo cows (24 normal cycling, 8 pregnant and 32 repeat-breeder), selected from two buffalo farms near Cairo during 1987 and 1988, were studied during thefirst 26 days after oestrus (day 0). Plasma progesterone concentrations were significantly (P&lt; 0·01) higher in pregnant than in cyclic (between days 3 and 5) and repeat-breeder (between days 0 and 8) animals. Concentrations of total unconjugated oestrogens were also highest (P&lt; 0·01) in the pregnant group between days 6 and 16. Cyclic and pregnant cows had higher (P&lt; 0·01) concentrations of plasma calcium between days 3 and 7, inorganic phosphorus at all times and glucose between days 2 and 8 than repeat-breeders. Plasma protein concentrations were greater at all times, except between days 6 and 8, in the first two groups. Analysis of the uterine fluid collected from cyclic and repeat-breeder buffalo cows revealed that concentrations of all biochemical components, except for calcium, were significantly (P&lt; 0·01) higher in flushings from the uterus of cyclic animals than from repeat-breeders at alltimes for inorganic phosphorus, between days 6 and 12 for glucose and on day 2 as well as between days 8 and 12 for protein. Large differences were found in calcium levels, especially on day12 when flushings from repeat-breeder cows contained more than six times the concentrations of this metabolite in uterine flushings from cyclic animals. The results suggested that reduced luteal function, related to atypical profiles of plasma biochemical components, during the oestrous cycle in repeat-breeder buffalo cows might provide the basis for altered syntheses and secretions of uterine calcium, phosphorus, glucose and proteins which are needed for embryo development.

Pregnancy diagnosis in sows by estimation of oestrogens in blood, urine or faeces

Concentrations of oestrone sulphate in blood and of total unconjugated oestrogens in faeces were measured during the oestrous cycle and early gestation. The level of these hormones in blood and faeces was consistently higher (blood, 100%; faeces, 69–100%) between Days 24 and 30 in pregnant than in non-pregnant sows. Therefore, early pregnancy diagnosis based on the concentration of oestrogens in blood, urine and faeces was performed on Day 27, 28 or 29 after service for a total of 290 sows. Blood samples (25 μl) were taken from the tail vein of 289 sows. One hundred urine samples (1 ml) were collected by inserting a cellulose sponge into the vagina and faeces samples (2 g) were taken from the rectum of 290 sows. Pregnancy diagnosis was made on the assumption that more than 2.79 ng oestrone sulphate/ml blood, 19.7 ng oestrogens/g faeces and 65.6 ng oestrogens/ml urine indicated a pregnant animal. The efficiency of the tests was determined by comparing the diagnosis based on oestrogen concentrations with the farrowing results. The oestrone sulphate concentration in blood, as measured by enzyme immunoassay on microtitre plates, showed that 265 of the examined sows were correctly diagnosed, an accuracy of 91.7%. Seven results were false negative and 17 false positive. The determination of oestrogens in urine by radioimmunoassay (RIA) showed that 98 of 100 examined sows were correctly diagnosed and 2 were false negative. According to the oestrogen concentration in faeces, measured by RIA, 271 sows (93.5%) were correctly diagnosed, 16 were false negative and 3 false positive.

Prolongation of gestation and changes in maternal steroid hormone concentrations during cold exposure of sheep in late pregnancy

ABSTRACTIn 40 ewes exposed to thermoneutral or cold environments during the last 5 to 6 weeks of pregnancy (experiment 1), and in 10 ewes treated in the same way during the last 3 to 9 days of pregnancy (experiment 2), cold exposure lengthened mean gestation times by 1·7 and 2 days respectively. This effect was statistically significant only in experiment 1. Blood samples were taken from the right atrium of ewes in experiment 2 and the concentrations of some hormones in the plasma were measured. Cortisol concentrations were higher in plasma from cold-exposed ewes than control ewes. Plasma progesterone concentrations were lower in cold-exposed ewes than control ewes during a period from 36 h before parturition to 36 h after parturition, but the changes in plasma total unconjugated oestrogens, 17a, 20o-dihydroxypregn-4-en-3-one and oestrogen sulphates were associated with parturition in the normal way.The mechanism underlying the prolongation of gestation during cold exposure requires further investigation; events that precede the change of steroid production by the placenta at parturition are most likely to be involved.

Transport of free and conjugated steroids from the boar testis in lymph, venous blood and rete testis fluid.

In 12 anaesthetized boars the concentrations of oestrone sulphate and dehydroepiandrosterone sulphate (DHAS) were 15- to 35-fold higher in lymph collected from a vessel in the spermatic cord than in testicular venous blood plasma from a vein in the spermatic cord. The concentrations of testosterone, total unconjugated oestrogens and dehydroepiandrosterone (DHA) were about twofold higher in lymph. The concentrations of all steroids studied were higher in testicular venous blood plasma than in arterial blood plasma (testosterone about sixfold; total unconjugated oestrogens about fourfold; oestrone sulphate about threefold; DHA and DHAS about twofold), but the concentrations of testosterone, total unconjugated oestrogens and oestrone sulphate in rete testis fluid were comparable to those in arterial blood plasma. Lymph flow from the pig testis was about 7% of plasma flow so that about 80% of the oestrone sulphate and DHAS produced by the testis leaves the organ in the lymph; the comparable values for testosterone, total unconjugated oestrogen and DHA were about 20%. In the 90-min period following an injection of human chorionic gonadotrophin there were substantial increases in the concentration of testosterone and smaller increases in the other steroids in arterial and spermatic venous blood plasma and in testicular lymph, but not in rete testis fluid; there were also small increases in lymph flow, but no change in blood flow.

Plasma levels of androstenedione, epitestosterone, testosterone and oestrogens in cows at parturition.

The concentration of total unconjugated oestrogens in the peripheral plasma of cows increased from 2.00 +/- 0.20 (S.E.M.) ng/ml 7 days before to 3.87 +/- 0.50 ng/ml 1 day before parturition and declined to values below 0.30 ng/ml on day 2 post partum. The concentrations of androstenedione, epitestosterone and testosterone remained approximately constant at 0.90 +/- 0.10, 0.92 +/- 0.08 and 0.40 +/- 0.20 ng/ml respectively during the last week of pregnancy. After parturition the concentration of the three androgens declined rapidly. Similar to data obtained in goats we did not find a marked increase in androgen levels in the peripheral blood of cows before parturition.

Placental production of progesterone in ovariectomized goats treated with a synthetic progestagen to maintain pregnancy.

Pregnant goats were ovariectomized or lutectomized and treated with medroxyprogesterone acetate. The circulating concentration of progesterone, which was reduced by 85% after ovariectomy or lutectomy, increased almost 3-fold between 120 and 140 days gestation, suggesting increased placental secretion. Measurement of veno-arterial differences across the uterus confirmed that an intrauterine organ was secreting progesterone at this time. Progesterone levels decreased (by 38%) in intact animals treated with medroxyprogesterone acetate alone. Concentrations of total unconjugated oestrogens were not altered by ovariectomy or lutectomy or by medroxyprogesterone acetate alone, but were related to the birth weight of the kids. Chronic treatment with medroxyprogesterone acetate reduced milk yield during lactation by up to 64%.

The effect of passive immunization against oestrogens on the onset of parturition in the ewe.

Six ewes were treated twice daily with intravenous injections of antiserum to oestrogens and 3 ewes received normal sheep serum from Day 140 of gestation until parturition. All 9 ewes experienced normal parturitions and produced healthy active lambs after similar gestation lengths. Progesterone and prostaglandin F concentrations in maternal jugular venous plasma were similar in the immunized and control ewes, but total unconjugated oestrogen concentrations were significantly higher in the immunized ewes (P less than 0.005). It is concluded that immunization of the ewe against total unconjugated oestrogens did not affect the normal occurrence of parturition.

Effect of fetal hypophysectomy on the initiation of parturition in the goat.

Fetal hypophysectomy performed between 97 and 130 days of gestation caused a significant (P is less than 0.005) prolongation of pregnancy in 5 goats in which every fetus was treated. Three of these goats gave birth spontaneously. Sham surgery or hypophysectomy of one fetus of twins had no effect on gestation length. Hypophysectomized kids, delivered after prolonged pregnancy, were significantly heavier than normal term kids (P is less than 0.005) and had lighter adrenals (P is less than 0.025). Measurements of maternal peripheral plasma concentrations of progesterone and total unconjugated oestrogens showed that the changes in goats carrying hypophysectomized fetuses were similar to those of normal pregnancy except that the prepartum oestrogen peak was absent, whether or not parturition occurred spontaneously.

Bilateral adrenalectomy of lambs in utero: effects on maternal hormone levels at induced parturition.

Progesterone, 17 alpha, 20 alpha-dihydroxypregn-4-en-3-one, androstenedione, total unconjugated oestrogen and oestrone sulphate have been measured by radioimmunoassays in maternal utero-ovarian venous, maternal peripheral venous and/or foetal posterior vena caval plasma from six sheep bearing bilaterally adrenalectomized lambs, in which premature parturition was induced by administration of glucocorticoid. Three of the ewes were overiectomized, and in one of these three animals the foetal testes were also excised, at the time of foetal adrenalectomy. Adrenalectomy was judged to be complete on the basis of plasma cortisol levels in the neonatal lambs, and by examination of the site of ablation at necropsy. In all cases foetal administration of glucocorticoid led to the onset of labour, and lambing, and in all animals the hormonal changes preceding parturition were indistinguishable (either qualitatively or quantitatively) from the changes observed in animals carrying intact lambs. Since therapy with glucocorticoid alone successfully compensates for ablation of the foetal adrenal cortex, it is suggested that glucocorticoid is the only adrenal product required to cause parturition, and that foetal adrenal secretion of androgens may be unnecessary.

Plasma oestrogen and progesterone in relation to superovulation and egg recovery in the cow.

Pregnant mares serum gonadotrophin (PMSG) was used in combination with prostaglandin F2alpha or its analogues to induce superovulation in 25 heifers. Total unconjugated oestrogen and progesterone were determined in peripheral plasma of these superovulated animals, and the levels compared with those found during the normal oestrous cycle. A very high level of oestrogen was found between day 3 and 6 after superovulation, and it seems likely that large unovulated follicles were responsible for the excess steroid. Similarly, progesterone levels were raised in the superovulated animal presumably due to production by the numerous corpora lutea. In two heifers, in which overstimulation of follicular development had occurred, there were no ovulations in one of the animals while in the other animal there were 16 ovulations but early regression of corpora lutea was indicated. It is concluded that the poor recovery of eggs on day 6 after superovulation could have been due to deleterious effects of high levels of oestrogen on either the motility of the genital tract causing the premature transport of eggs, or the properties of the zona pellucida.

The effect of serial uterine biopsies and hysterectomy on peripheral blood levels of total unconjugated oestrogen and progesterone in the bitch.

Department of Surgery and Obstetrics, Royal Veterinary College Field Station, Hawkshead Lane, North Mimms, Nr Hatfield, Hertfordshire (Received 11th March 1975) The role of ovarian steroids in the aetiology of cystic endometrial hyperplasia in the bitch has been under discussion for some time. Earlier workers thought that this condition was due to abnormal oestrogen production (Hetzel, 1935; Bloom, 1954; Schulze, 1955). Teunissen (1952) and Dow (1959), however, produced evidence suggesting that prolonged high levels of progesterone were the cause of cystic endometrial hyperplasia in the bitch. The present work reports the changes in total unconjugated oestrogen and progesterone concentrations in the peripheral blood of bitches subjected to serial biopsies, which result in the development of uterine lesions without hormone treatment (Hadley, 1975a), and the effect of hysterectomy on the levels of these steroids. One multiparous beagle, Bitch A, and two nulliparous mongrels, Bitches F and J, were used in this

Unconjugated oestrogen and progesterone concentrations in the blood of bitches with false pregnancy and pyometra.

The changes in total unconjugated oestrogen and progesterone concentrations in the peripheral blood of one bitch throughout a false pregnancy were measured. The levels of these hormones detected in 11 bitches when examined during a false pregnancy, and in 13 other bitches with pyometa are also reported. Oestrogen and progesterone concentrations were within normal limits in both of these conditions where single samples were obtained, but the bitch with false pregnancy studied in detail showed a raised oestrogen level during metoestrus. The significance of these results is discussed in relation to previous studies on the aetiology of false pregnancy and pyometra.

Stimulation by oxytocin of prostaglandin F levels in uterine venous effluent in pregnant and puerperal sheep

The purpose of this work was to investigate the effect of oxytocin on prostaglandin F (PGF) concentrations in uterine venous effluent. PGF was measured in utero-ovarian venous plasma from three pregnant ewes and in posterior vena caval plasma, from two puerperal ewes, during oxytocin administration. Oxytocin caused 4.9 – 5.3-fold increases in PGF concentrations in the pregnant animals, the response increasing towards term. In the puerperal animals oxytocin caused 3.7 – 17.2-fold increases in PGF concentrations with a marked latency in the response. Measurement of uterine activity and progesterone and total unconjugated oestrogen concentrations indicated that neither uterine contractions nor a decreased uterine blood flow accounted for the elevated PGF levels stimulated by oxytocin.

Parturition in the guinea-pig; plasma levels of steroid hormones, steroid-binding proteins, and oxytocin, and the effect of corticosteroids, prostaglandins and adrenocorticotrophin.

SUMMARY Parturition in the guinea-pig is not preceded by any consistent change in the maternal plasma concentrations of progesterone, total unconjugated oestrogens or corticosteroids, or by a significant change in the concentration of progesterone-binding globulin (PBG). The onset of parturition was delayed by high doses of oestrogens (stilboestrol and oestradiol), but was not affected by oestriol or an antiserum raised against oestradiol. Premature parturition was achieved by the intra-carotid infusion of adrenocorticotrophin or prostaglandins (PGF2α, PGE2, I.C.I. 80,996) in conscious animals with indwelling catheters. I.C.I. 80,996, a potent analogue of PGF2α, induced parturition in all seven guinea-pigs treated; delivery occurred within 6 h of starting the infusion in six animals, and within 48 h in the seventh. The undesirable side-effects that accompanied treatment with PGF2α or PGE2 were not encountered with I.C.I. 80,996. Parturition induced experimentally resembled normal delivery but was not preceded by any significant change in the maternal levels of progesterone, total unconjugated oestrogens, corticosteroids, PBG or CBG in the circulation. Oxytocin was not detected until the delivery of the first foetus. Parturition was not induced by maternal or foetal injections of corticosteroids or dexamethasone. Earlier findings are confirmed that the foetal adrenal grows steadily throughout late pregnancy and, unlike the foetal lamb adrenal, undergoes no rapid phase of growth immediately before term. Foetal adrenal weight decreased relative to foetal body weight. The trigger for parturition in this species remains unidentified.

Control of utero-ovarian venous prostaglandin F during labour in the sheep: acute effects of vaginal and cervical stimulation.

SUMMARY Simultaneous measurements of prostaglandin F, total unconjugated oestrogens and progesterone have been made in utero-ovarian venous or posterior vena caval plasma from pregnant ewes during parturition. In all cases, levels of oestrogens and prostaglandin F increased before delivery, after a decrease in the level of progesterone. In four out of six sheep, during both spontaneous and dexamethasone-induced labour, increases in the levels of oestrogens and prostaglandin F occurred in parallel. In the other two animals, levels of prostaglandin F increased before those of oestrogens. The increases in prostaglandin F consistently preceded any measurable increase in uterine activity, suggesting levels were not raised as a consequence of labour. Infusion of oestrogen to two dexamethasone-treated animals resulted in increased utero-ovarian venous prostaglandin F levels within 2–3 h. These findings support previous evidence indicating that levels of prostaglandin F may be controlled by oestrogen and progesterone. Manual examination of the cervix, with associated distension of the vagina, resulted in dramatic increases in the level of utero-ovarian venous prostaglandin F during the last 13 h of gestation, both in dexamethasone-induced labour and in labour of natural onset. Since expulsion of the foetus also results in vaginal distension, this finding raises the possibility that the very high levels of prostaglandin F observed at delivery may be caused by tactile stimulation of the vagina.

Maternal plasma oestrogen and progesterone levels during therapeutic abortion induced by intra-amniotic injection of prostaglandin F 2 .

SummaryPlasma 17β‐oestradiol, total unconjugated oestrogens and progesterone levels were measured in ten patients in the second trimester of pregnancy who were undergoing abortion by intra‐amniotic injection of prostaglandin F2α (PGF2α). The correlation between total unconjugated plasma oestrogens and 17β‐oestradiol was highly significant (r =+0.92; p&lt;0.001). A similar positive correlation between total unconjugated plasma oestrogen and progesterone was observed (r =+0.66; p&lt;0.001). The concentration of these steroids in samples, taken at intervals during normal pregnancy, showed considerable variation. Following administration of PGF2α no consistent change was seen in plasma steroid concentrations until after delivery of the fetus and placenta. PGF2α therefore appears to have no direct effect on oestrogen and progesterone biosynthesis and may act principally by direct stimulation of myometrial contractility.

Concentrations of oestrogen and progesterone in the plasma of non-pregnant, pregnant and lactating guinea-pigs.

SUMMARY A competitive protein-binding assay of progesterone and a radioimmunoassay of total unconjugated oestrogens were evaluated and employed in the measurement of these steroids in the plasma of guinea-pigs at different times during the reproductive cycle. Production rates (PR) were calculated from the product of the endogenous steroid concentration and its metabolic clearance rate. During the oestrous cycle, plasma progesterone levels rose from undetectable levels at the time of ovulation to 2·8 ± 0·33 (s.e.m.) ng/ml 5 days later; PR was 0·26 mg/day. During pregnancy, plasma progesterone concentrations in post-partum mated guinea-pigs rose from 15 ng/ml at day 15 post coitum (p.c.) (PR, 0·65 mg/day) to a peak value of 329 ± 14 ng/ml by days 30 to 45. The concentration fell 51–55 days p.c. (160 ± 14·7 ng/ml), but rose before parturition to 258 ± 22 ng/ml. After day 20 p.c., PR was 1·24 ± 0·3 mg/day. After parturition, plasma progesterone levels fell rapidly and during lactation were about 10 ng/ml (PR, 0·4 mg/day). Total unconjugated oestrogens in arterial plasma were not detected in early pregnancy, but rose from values of 12·8 ± 1·9 pg/ml (days 31–35) to 31·0 ± 5·2 pg/ml (days 56–60). There was a slight fall before, and a rapid one after parturition. The ratio of progesterone to oestrogen in plasma fell during pregnancy and reached its lowest values between days 55 and 60.