OBJECTIVE

The effect on blood pressure of oral replacement' doses of exogenous oestrogen may depend on the type and dose of oestrogen administered. This study was designed to compare with placebo the effect of once daily treatment with a 'natural' oestrogen, piperazine oestrone sulphate, in two different doses and a semisynthetic oestrogen, ethinyloestradiol, on clinic and ambulatory blood pressure and the renin-angiotensin system in postmenopausal women.

METHODS

Twenty-four normotensive postmenopausal women (median age 54 years, range 47-60 years) participated in the study which used a double-blind crossover design. For each subject there were four randomized treatment phases, each lasting 4 weeks. The separate treatments administered once daily were 0.625 mg oestrone sulphate, 2.5 mg oestrone sulphate, 0.02 mg ethinyloestradiol and matching placebo. Clinic blood pressure, heart rate and weight were measured weekly with the mean values of weeks three and four of each phase used for analysis. Ambulatory blood pressure and biochemical measurements were performed in the final week of each phase.

RESULTS

Twenty-four subjects entered and 22 completed the randomized phases of the study. Compared with the placebo phase, end-of-phase mean clinic diastolic blood pressure was reduced in subjects taking the semisynthetic oestrogen (P < 0.01) but was unchanged in those taking the 'low' and 'high' dose natural oestrogen. Mean clinic systolic blood pressure was also unchanged by any of the oestrogen treatments. Ambulatory night-time systolic, diastolic and mean arterial blood pressures were reduced with the low-dose natural and semisynthetic oestrogen treatments compared with placebo (P < 0.01), whereas there was no significant effect of the oestrogen treatments on ambulatory daytime blood pressures. A reduction in clinic and ambulatory heart rate was observed with the high-dose oestrone and semisynthetic oestrogen treatments. There was a dose-dependent increase in plasma renin substrate and decrease in plasma renin concentration with all active treatments; however, there was no change in plasma renin activity or plasma aldosterone concentration.

CONCLUSIONS

In normotensive postmenopausal women, replacement doses of natural and semisynthetic oestrogen reduce night-time ambulatory blood pressure with either no change or a small reduction in clinic blood pressure. Reduction in blood pressure is not explained by reduced activity of the renin-angiotensin system but could have a component of reduced central sympathetic drive consistent with the decreased heart rate.

The hormonal status of thirteen chronic male alcoholics with histologically proved alcoholic liver cirrhosis and that of sixteen non-cirrhotic chronic alcoholics with a similar drinking history were studied after the abstinence of 7-14 days. Low levels of plasma testosterone and moderately elevated concentrations of plasma LH were seen in cirrhotics but not in non-cirrhotics. In cirrhotics, testosterone values showed positive correlations with levels of serum albumin and plasma prothrombin. The responses of LH and FSH secretions to LHRH stimulation were similar in the two groups as were the basal FSH values. Plasma concentrations of oestradiol were within normal limits in all patients. In both groups however, basal levels of plasma PRL and oestrone were increased, significantly more so in cirrhotics than in non-cirrhotics. The latter group was characterized by an exaggerated response of PRL secretion to TRH stimulation. SHBG concentrations were within normal range in both groups. In conclusion, our results emphasize the role of alcohol-induced liver damage in the pathogenesis of sex hormone disturbances of chronic male alcoholics without neglecting, however, the direct effects of alcohol abuse itself.

The aromatase enzyme, which converts androstenedione to oestrone, regulates the availability of oestrogen to support the growth of hormone-dependent breast tumours. Cytokines, such as interleukin 6 (IL-6) and tumour necrosis factor alpha (TNFalpha) or prostaglandin E(2) (PGE(2)), can stimulate aromatase activity. These factors may originate from cells of the immune system that infiltrate breast tumours. Paclitaxel, which is used in the treatment of breast cancer, stabilizes microtubules and has previously been shown to rapidly down-regulate TNF-receptors on human macrophages. The endogenous oestrogen metabolite, 2-methoxyestradiol (2-meOE2), also acts to stabilize microtubules. In this study, we have examined the ability of paclitaxel or 2-meOE2 to antagonise TNFalpha-stimulated aromatase activity in stromal fibroblasts derived from normal or malignant breast tissues. Paclitaxel inhibited basal and TNFalpha-stimulated aromatase activities by 88% and 91% respectively. 2-MeOE2 also reduced basal and TNFalpha-stimulated aromatase activities by 46% and 56% respectively. Both paclitaxel and 2-meOE2 also inhibited stimulation of aromatase activity by IL-6 plus its soluble receptor and PGE(2). The 16alpha-hydroxylated derivative of 2-meoE2 and 2-meOE3, which does not bind to microtubules, was less effective at inhibiting TNFalpha-stimulated aromatase activity. Increased 2-hydroxylation of oestrogens, and subsequent formation of their 2-methoxy derivatives, may be associated with a reduced risk of breast cancer. It is possible that the pathway of oestrogen metabolism may influence the ability of stromal cells to respond to cytokine stimulation.

In athymic mice, Natural Killer (NK) cells influence the take rate and growth of human malignant tissue xenografts. To confirm preliminary results, comparative experiments were conducted to study the effects of beta-carotene, oestrone and their association on the cytolysis mediated by spleen NK cells from athymic mice receiving these different treatments. Target cells consisted of YAC-1 malignant cells. With a 65% increase of cytolysis (ratio effector/target 50:1), beta-carotene induced a significant activation of NK cells (p < 0.002). This effect could be attributed to its antioxidant properties and confirmed by a moderate increase in erythrocyte glutathione peroxidase activity. On the contrary, oestrone resulted in a significant decrease of cytolysis (p < 0.001). In this case, the prooxidant properties of oestrone could explain its effect on NK cells and agree with the increase of intracellular reduced glutathione level observed. When mice received the combination beta-carotene-oestrone, their opposite effects on NK cell activity were counterbalanced, leading to a moderate change of cytolysis.

Ovarian and peripheral plasma concentrations of oestrone (E1), oestradiol (E2), androstenedione (A), testosterone (T), progesterone (P) and 17 alpha-hydroxy-progesterone (17 alpha OH-P) were assayed in 20 healthy post-menopausal women undergoing hysterectomy because of uterine fibromatosis. Significant differences were found between the ovarian and peripheral levels of E1 (P less than 0.01), E2 (P less than 0.001), A (P less than 0.01), T (P less than 0.001) and P (P less than 0.001). Analysis of the possible relationships between peripheral and ovarian levels of the six steroids considered and the patients' clinical characteristics revealed a positive correlation in only three cases, viz. between body weight and peripheral levels of E1 and E2, between E1 and E2 peripheral levels and between body weight and the E1/A ratio. The ovarian-peripheral gradient was calculated for each patient and was considered significant only if the ovarian peripheral difference exceeded the sum of each concentration multiplied by twice the maximal coefficient of variation of the assays used (12%). This gradient was significant in 75% of patients for T, in 45% for A, in 35% for E2, in 25% for E1, in 35% for P and in 30% for 17 17 alpha OH-P. Our findings confirm that circulating oestrogens in post-menopausal women originate mainly from the peripheral conversion of ovarian and adrenal androgens and that the ovary still continues to produce androgens. They also provide evidence that the ovary, at least in some post-menopausal subjects, can be a potential source of oestrogens and progestogens.

The urinary excretion of oestrone (E1), oestradiol (E2) and oestriol (E2) was measured in 42 obese post-menopausal women before and 6-12 mth after their participation in a weight reduction programme. The method of inducing weight loss was based on modification of eating behaviour without specific changes in dietary composition. Urinary oestrogen, as a ratio to creatinine, were measured by a specific radioimmunoassay after purification of the specific oestrogen fraction. Before weight reduction efforts, there is a significant correlation among E1, weight and the Quetelet-index and between E3 and the Quetelet-index. These correlations have disappeared after weight reduction. There is a significant positive correlation between changes in body-weight and changes in the excretion of E1, E3 and total oestrogens. There was no significant change in the so-called oestrogen ratio (E1 + E2/E3) in relation to change in body weight. With respect to the statistical association between endometrial cancer, breast cancer and overweight, our data give support to the concept that intervention programmes on weight reduction may influence both the incidence and the prognosis of these two diseases.

Assays of first morning urine samples for oestrone-3-glucuronide, LH and pregnanediol-3-glucuronide, were used to study endocrine function and return to ovulation in 18 subjects following spontaneous miscarriage. On the basis of the endocrine data, ovulation occurred in all 18 women in the cycle prior to first menses at a mean of 29 days post-partum (range 13-103 days) with one subject conceiving in that cycle. Compared with the second cycle, the first cycle after spontaneous abortion had similar levels of follicular phase peak ovulatory oestrone excretion but lower levels during the late luteal phase (P less than 0.02), lower levels of peak LH (50.5 IU/g creatinine (C) cf. 68.8 IU/g C; P less than 0.04) and lower late secretory peak pregnanediol (4.6 mg/g C cf. 6.1 mg/g C; P less than 0.02). The mean luteal phase length of 12.9 days in the first cycle was shorter than the mean of 14.4 days in the second cycle (P less than 0.02). These data show that, although there is some disturbance of endocrine function in the first cycle after spontaneous abortion, the majority of women have a rapid return to ovulation, making the early use of contraception necessary for those wishing to avoid conception.

The present study investigated the presence of a single-nucleotide polymorphism (G>> T) at base -8 upstream of ATG in 5' untranslated region of cytochrome b5 (CYB5A) gene in Swedish pig populations and evaluated the significance of this polymorphism for androstenone and skatole levels, sexual development and performance parameters in pigs. Frequencies of the T allele were 6.7% for Swedish Yorkshire × Landrace crossbred pigs (n = 245), 6.5% for Swedish Yorkshire (n = 99) and 12.8% for Landrace breed (n = 74). No deviations from Hardy-Weinberg equilibrium were observed in the investigated populations. In Swedish Yorkshire × Landrace crossbred entire male pigs (n = 193), plasma samples were analysed for skatole, androstenone, testosterone and oestrone sulphate, and fat samples were analysed for androstenone, skatole and free oestrone. Additionally, testis weight and bulbourethral gland length for crossbred pigs were recorded. Plasma androstenone levels were significantly lower in the G/T genotype at 90 kg live weight compared with the wild G/G genotype at the same live weight (P = 0.006). In heavier pigs, plasma androstenone levels did not differ between genotypes (P = 0.382). Fat androstenone levels were not affected by CYB5A genotype (P = 0.252). Skatole levels in the G/T genotype at 115 kg live weight were lower compared with those in the G/G genotype in plasma (P = 0.048) and fat (P = 0.028), although no differences were observed in lighter pigs. Testis weight, bulbourethral gland length, testosterone and oestrone sulphate levels in plasma, and oestrone levels in fat were not affected by genotype. We concluded that the presence of the T allele in the CYB5A gene resulted in lower androstenone levels in plasma, and lower skatole levels in fat and plasma; this reduction, however, was dependent on the live weight of the animals. Reproductive hormones and growth rate did not differ between the pigs of different genotypes, whereas a higher lean meat content was found in the G/T genotype in comparison with the G/G genotype. The practical application of those results in Sweden is doubtful because of lack of the effect on androstenone in fat and the low frequency of the T allele in the studied Swedish pig populations.

In the analysis of steroid hormones careful attention is usually paid to blood collection and plasma storage. However, the appropriate care of samples cannot always be assured in routine work with steroids. Therefore, the stability of cortisol, aldosterone, 17-hydroxyprogesterone, testosterone, androstenedione, dehydroepiandrosteronesulphate, oestrone, oestradiol, sex hormone binding globulin (SHBG) and, the binding of testosterone and cortisol to plasma proteins in blood and plasma were studied before and after various handling procedures. Ten cycles of alternate freezing and thawing of plasma did not significantly affect the levels of the steroids or their plasma binding. The greatest differences, compared with controls, were seen for aldosterone (-6.2%) and oestradiol (-5.3%). Plasma storage at -28 degrees C was hardly superior to a 4 days storage at 4 degrees C (refrigerator) or 22 degrees C (room temperature). Although androstenedione (-10.9%), oestrone (-10.2%) and oestradiol (-12.2%) levels decreased by more than 10%, the means of all analyses were still in the 2 SD range. Even SHBG and the steroid binding were only slightly affected by temperature. When whole blood was stored at 4 degrees C or 22 degrees C, the resulting values differed from those obtained with plasma, but the differences were usually less than 10%. Although the levels were within the 2 SD range, whole blood showed a decrease of 12.3% for aldosterone and 14.5% for androstenedione. In contrast, plasma binding of testosterone (25.9%) and cortisol (15.1%) were substantially affected by storage at 22 degrees C in whole blood. It is concluded that repeated freezing and thawing of plasma, or storage at various temperatures have only a small effect on the measured levels of steroids and their plasma binding. Although it is not advisable, even whole blood may be used for the analysis of steroid concentrations.

The mouse placenta possesses a soluble oestrogen sulphotransferase activity which increases markedly from at least 12 days of gestation until term. At about 16 days of gestation, a similar activity is found in the uterus. This activity also increases until term and disappears rapidly post partum. The uterine enzyme activity appears to require the presence of the foetal unit for its onset, since unoccupied horns, whether their endometrial stromal cells are differentiated to decidual cells or not, are essentially devoid of it. Uterine cytosols from non-pregnant mice are also inactive in this respect. In late gestation, the uterine sulphotransferase is confined to the decidua basalis, the areas to which the placentas are attached. The sulphotransferase(s) of placenta and uterus has an absolute requirement for 3'-phosphoadenosine 5'-phosphosulphate, and possesses little activity in the absence of exogenous thiol groups. Stimulation is also seen in the presence of Mn2+, Mg2+ or Ca2+. Oestrone and oestradiol, and to a lesser degree oestriol, are substrates for the enzyme(s), whereas testosterone, cortisol and dehydroepiandrosterone are not. Oestrone and oestradiol at higher concentrations (1.0-1.5 microM) completely inhibit the enzyme(s). These enzymes could play a role in altering tissue concentrations of active oestrogens during gestation in the mouse. Oestrogen sulphotransferase activity is low or absent in reproductive tissues of the pregnant rat.

The pharmacokinetic properties and biotransformation of two orally active oestrogens, piperazine oestrone sulphate (PE1S, 2.5 mg/day) and oestradiol valerate (E2V, 2.0 mg/day), given alone or in combination with levonorgestrel (LNG, 250 micrograms/day) were compared in 8 post-menopausal women, using a randomized cross-over design. The end points measured in peripheral plasma included oestrone (E1), oestradiol (E2), oestriol (E3), oestrone sulphate (E1S), oestradiol sulphate (E2S) and oestriol sulphate (E3S). In addition, LNG and sex-hormone-binding globulin SHBG concentrations were also assessed. The plasma levels of E3 were invariably below the detection limit (220 pmol/l). The levels of all the other oestrogens analyzed were consistently higher and the area under the curve significantly greater (except in the case of E3S) following PE1S administration than those recorded after E2V ingestion. The terminal half-lives of the circulating oestrogens measured after PE1S administration did not differ from those found after E2V administration. After 21 days of PE1S administration (in combination with LNG for the last 10 days), the maximum levels of all the oestrogens (except those of E2) were significantly higher than those seen after the first dose. No such difference was observed after E2V administration. There was no difference between the effects of the two treatment regimens with regard to the E1/E2 ratios, but the E1/E1S ratios were significantly lower after PE1S treatment than after E2V administration. It is concluded that, compared with an equivalent dose of PE1S, daily repeated oral administration of E2V yields consistently lower peripheral plasma levels of E2 and its principal metabolites. However, in contrast to PE1S therapy, prolonged administration of E2V does not result in an accumulation of the circulating oestrogens measured.

To investigate the sex-hormone profiles associated with chronic alcoholism in women we examined 16 non-cirrhotic alcohol abusers (aged 18-46 years). They were admitted for the treatment of alcoholism (duration of 2-16 yrs) to a social hospital for 6 weeks. Their mean daily alcohol consumption was 170 g. Blood samples for serum LH, FSH, prolactin (PRL), oestrone (E1), oestradiol (E2), progesterone (P), 17-alpha-hydroxyprogesterone (17-OHP), androstenedione (A) and dehydroepiandrosterone (DHEA) were drawn three times a week during the hospital stay. Similar blood samples were taken from 10 control women during one menstrual cycle. The cycles were anovulatory in two patients and in none of controls. Serum LH and FSH levels were similar in alcoholic and control women but serum concentrations of PRL were increased 2-4-fold in alcoholic women. In the patients serum, concentrations of E1 and E2 tended to be lower during the follicular and midcycle phases, as did those of P and 17-OHP during the luteal phase. Compared with the controls, serum levels of A were increased 2-3-fold in the patients. A parallel difference between the two groups was seen in serum DHEA concentrations. We conclude that until liver injury, even heavy alcohol drinking has only minor effects on the secretion of gonadotrophins and ovarian steroids. Hypersecretion of PRL and adrenal androgens may well be an initiating mechanism for sexual dysfunction of female alcoholics.

A delipidation procedure based on treatment with charcoal at pH 3 has been applied to highly purified rat alpha 1-foetoprotein preparations. The oestrogen binding properties of the delipidated proteins have been studied with an equilibrium dialysis technique, and compared with the properties of the untreated foetal protein, as well as those of preparations reconstituted from the defatted alpha 1-foetoprotein and the removed lipids. An important increase has been evidenced for the binding levels of oestrone, oestradiol-17 beta and diethylstilboestrol by the delipidated alpha 1-foetoprotein. A reversal of this effect has been obtained by incubating the delipidated protein either with the lipids extracted from the purified alpha 1-foetoprotein or with a potent competitor of the rat alpha 1-foetoprotein-oestrogen interaction, designated as 'L', previously demonstrated and isolated from whole rat sera, and tentatively characterized as a mixture of fatty acids. Scatchard analysis of the oestrone and oestradiol-17 beta binding parameters show that the enhanced fixation of the hormones after defatting is primarily due to a two-fold increase of the apparent number of binding sites/mol alpha 1-foetoprotein. The results are interpreted in terms of the probable, at least partial, identity between the lipids closely associated with the pure alpha 1-foetoprotein and the fatty acid mixture 'L' isolated from whole sera. The possible biological role of complex interplay between oestrophilic alpha 1-foetoproteins, phenolsteroids and fatty acids in the control of oestrogen levels during development is discussed briefly.

OBJECTIVE

To study the hormonal changes resulting from long-term use of the non-steroidal anti-androgen Casodex.

METHODS

A randomized, placebo-controlled study was carried out on 27 patients with benign prostatic hyperplasia (BPH). Fourteen patients received Casodex 50 mg daily for 24 weeks and 13 received a placebo. The patients were followed up for a further 24-week period.

RESULTS

Serum concentrations of luteinizing hormone (LH) increased by an average of 40% while follicle-stimulating hormone (FSH) remained unchanged. Testosterone increased by 35%, oestradiol by 29% and oestrone by 23%; all changes were statistically significant. Levels of androstenedione and dihydrotestosterone increased by 11% and 15%, respectively, but these increases did not reach statistical significance. A non-significant increase was also observed for sex hormone-binding globulin. The hormonal changes were reversible upon discontinuation of therapy. Prolactin and dehydroepiandrosterone-sulphate levels did not change.

CONCLUSIONS

This study indicates that Casodex, due to competitive inhibition of central androgen receptors, increases LH secretion, thus causing increased production and increased metabolism of testosterone.

During late bovine pregnancy, several hormones are involved to maintain and develop a successful result with a live calf. These hormones are e.g., progesterone, high levels during the whole pregnancy period, originating from the corpus luteum, maternal adrenals and placenta. Oestrone sulphate, oestrone in its conjugated form, shows elevated levels from about mid-pregnancy until the third stage of parturition (expelling of the fetal membranes). For the onset of normal parturition and the parturition process as such, a change from progesterone to oestrone synthesis is crucial. The increasing levels of oestrone are time-related to an increased synthesis of prostaglandin F(2alpha) (reflected as elevated levels of 15-ketodihydro-PGF(2alpha)) causing prepartal luteolysis and several hormones are then involved in the labour process such as prostaglandin F(2alpha), cortisol and oxytocin. Cortisol might also be an indicator of stressful events for the dam. Levels of pregnancy associated glycoproteins (PAGs), originating from the trophoblastic binucleate cells, are increasing during the last 10 days prior to parturition. All the mentioned hormones have certain functions during pregnancy, more or less understood. However, could deviations from the expected profiles during late bovine pregnancy indicate impaired fetal well-being or be of importance for reproductive performance during the postpartum period? Abortions, stillbirths or dystocia are situations where endocrine profiles might predict the status of the calf. There are two possible approaches to study the endocrine changes in late pregnancy-to follow spontaneous cases of normal or impaired pregnancies or to experimentally disturb the gestation or induce parturition. We have in one study followed pregnant animals to depict reproductive disturbances, both animals with expected normal parturitions and animals where the sire of the calf has given rise to a high incidence of stillborn calves. The number of stillborn calves or dystocia has been small and so far it has not been possible to obtain a clear picture of the usefulness of endocrine parameters to follow fetal well being, but some of the hormonal parameters show a deviating profile. In a small group of animals with induced parturition (PGF(2alpha)), two out of three had parturition problems and one of these animals had a stillborn calf. All three animals had retained fetal membranes. It was possible to demonstrate a deviating endocrine profile in the cow having the stillborn calf in the sense of higher levels of progesterone, cortisol and 15-ketodihydro-PGF(2alpha) at the time of parturition. In both animals with dystocia the levels of oestrone sulphate after parturition were more sustained. Increasing and high levels of PAGs were only demonstrated in the animal with a normal parturition. These studies are ongoing, aiming at finding changes in endocrine profiles related to impaired pregnancies.

OBJECTIVE

The endogenous oestrogens have important biological functions in men as well as in women. Because 17beta-oestradiol and oestrone are also formed in the male body, these aromatic oestrogens are generally thought to be responsible for exerting the required oestrogenic functions in the male. In the present study, we tested the hypothesis that some of the non-aromatic steroids that are androgen precursors or metabolites with hydroxyl groups at C-3 and/or C-17 positions may also be able to serve as ligands for the oestrogen receptors (ER) in the male.

METHODS

A total of sixty non-aromatic steroids (selected from families of androstens, androstans, androstadiens, oestrens and oestrans) were analysed for their ability to bind and activate the human ERalpha and ERbetain vitro and in cultured cells.

RESULTS

Six of the non-aromatic steroids, that is, 5-androsten-3beta,17beta-diol, 5alpha-androstan-3beta,17beta-diol, 5(10)-oestren-3alpha,17beta-diol, 5(10)-oestren-3beta,17beta-diol, 4-oestren-3beta,17beta-diol and 5alpha-oestran-3beta,17beta-diol, were found to have physiologically relevant high binding affinity ( approximately 50% of that of oestrone) for human ERalpha and ERbeta. These non-aromatic steroids also activated the transcriptional activity of human ERs and elicited biological responses (such as growth stimulation) in two representative ER-positive human cancer cell lines (MCF-7 and LNCaP) with physiologically relevant potency and efficacy. Molecular docking analysis of these six active compounds showed that they could bind to ERalpha and ERbeta in a manner similar to that of 17beta-oestradiol.

CONCLUSIONS

These results provide evidence for the possibility that some of the endogenous androgen precursors or metabolites could serve as male-specific ER ligands.

Mifepristone (RU 486) is a potent antigestagen and antiglucocorticoid which when given at a dose of 25-600 mg disrupts folliculogenesis, inhibits ovulation and induces menses in healthy women. This study reports the effects of much lower doses of mifepristone than used previously, given for the duration of a complete menstrual cycle. Healthy female volunteers (n = 11) with regular menstrual cycles were given mifepristone at a daily dose of 5 mg (n = 6) or 2 mg (n = 5) for 30 days, beginning immediately after an ovulatory placebo cycle. Mifepristone prevented menstruation for the duration of the treatment period, with recurrence of menses 15-29 days after replacement of mifepristone with placebo. Daily mifepristone given in either 5 mg or 2 mg doses inhibited ovulation, as indicated by the lack of a rise in urinary pregnanediol excretion. The excretion of oestrone glucuronide in urine rose during treatment, suggesting ovarian follicular development. Inhibition of ovulation appeared to result from a failure of the positive feedback effect of oestradiol on the hypothalamo-pituitary axis, as no surges of luteinizing hormone were seen despite pre-ovulatory levels of oestrone glucuronide being measured during exposure to mifepristone. The cycle immediately following treatment was shorter than the pre-treatment cycle, with lower peak levels of pregnanediol glucuronide, suggesting an inadequate luteal phase. Recovery from the effects of mifepristone treatment was more rapid after 2 mg than after 5 mg and one subject conceived in the immediate post-treatment phase, indicating adequate ovulation and luteinization.(ABSTRACT TRUNCATED AT 250 WORDS)

The aim of this study was to determine the effect of intrauterine Escherichia coli infusion on the patterns of plasma LH, prolactin, progesterone, androstenedione, testosterone, oestrone, oestradiol-17beta, cortisol and 13,14-dihydro-15-keto-prostaglandin F2alpha (PGFM) in gilts during the oestrous cycle. On day 4 of the oestrous cycle (day 0), 25 mL of saline or 25 mL of Escherichia coli suspension, containing 10(7) colony forming units x mL(-1), was infused once into the each uterine horn in group I or II respectively. The control gilts developed a new oestrous cycle at the expected time but not bacteria-treated. Endometritis and vaginal discharge developed in all gilts after Escherichia coli infusion. The administration of Escherichia coli resulted in a reduction of plasma levels of LH, prolactin, oestrone and oestradiol-17beta (P < 0.05-0.001), mainly on days 15-18 after treatment (expected perioestrous period). During this time, the plasma androstenedione level was elevated (P < 0.05-0.001) after bacteria infusion. In the gilts receiving bacteria, progesterone concentration decreased from day 8 after treatment and was low until the end of the study (P < 0.05-0.001). On days 8-12 after bacteria administration, the level of PGFM was higher (P < 0.001) than that found in the control group. These results suggest that the developing inflammatory process of the endometrium in gilts following Escherichia coli infusion significantly affects the pituitary-ovarian axis function as well as prostaglandin production leading to anoestrus.

Bisphenol A (BPA) is a ubiquitous chemical suspected to possess oestrogenic hormonal activities. Male population studies suggest a negative impact on testicular function. As Sertoli cell proliferation occurs during fetal or early postnatal life, it is speculated that oestrogenic environmental exposures may influence mature testicular function. Among 705 Western Australian Pregnancy Cohort (Raine) Study men aged 20-22 years, 404 underwent testicular ultrasound examination (149 had maternal serum available), and/or 365 provided semen (136 had maternal serum) and/or 609 serum samples for sex steroids, gonadotrophins and inhibin B analysis (244 had maternal serum). Maternal serum collected at 18 and 34 weeks' gestation was pooled and assayed for concentrations of total BPA (free plus conjugated) as an estimate of antenatal exposure. Testicular volume was calculated by ultrasonography, and semen analysis performed. Serum LH, FSH and inhibin B were measured by immunoassay; testosterone, oestradiol, oestrone andBPA were measured by liquid chromatography-mass spectrometry. BPA levels were detectable in most (89%) maternal serum samples. After adjustment for maternal smoking, abstinence and varicocele, sperm concentration and motility were significantly correlated to maternal serum BPA (r = 0.18; P = 0.04 for both). No other associations of maternal serum BPA with testicular function were observed.

Five men with advanced breast cancer were treated with aminoglutethimide (AG) plus replacement dose hydrocortisone. None of the 4 patients with intact testes responded, although 3 did so subsequently to tamoxifen. The previously orchidectomized patient responded to aminoglutethimide for 14 months. Oestrone and oestradiol were suppressed by AG in all patients, but not to the levels achieved by orchidectomy. AG produced substantial further oestrogen suppression in the orchidectomized patient and should only be used after orchidectomy.

Plasma oxytocin concentrations were measured during late pregnancy, parturition and lactation in the miniature pig. Measurements were made of plasma oestradiol, oestrone and progesterone to determine whether there was any relationship between the concentrations of oxytocin and these steroids in the circulation. Plasma oxytocin concentrations were low or undetectable in late pregnancy. Rises of up to 68.8 mum./ml were seen at the time of delivery of the foetuses and at the expulsion of the placenta. The only steroid that seemed to relat to oxytocin release was progesterone. Oxytocin release was consistently seen when progesterone concentrations had fallen to below 10 ng/ml but no increase in concentration was observed while oestrone and oestradiol increased to their maximum concentrations of 3.86--11.6 and 0.43--0.70 ng/ml respectively. During lactation, when both oestrogen and progesterone concentrations were low, suckling caused the levels of oxytocin to increase to 7.4 muu./ml. These increases were greater during the first 2 weeks of lactation than later.