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.

During 1 h, median 976 mmol ethanol in 5.5% glucose was administered i.v. to six healthy female volunteers (aged 26-37 years) in the luteal phase of the menstrual cycle. The median maximal blood ethanol concentration was median 33.5 mmol/l and serum ethanol concentrations of 2 mmol/l were reached after 8 h. Four of the women participated in a control experiment with infusion of an equal volume of glucose 5.5%. Venous blood samples were drawn 5 times during the 24-h follow up period. Serum concentrations of sex steroids and pituitary hormones decreased in both ethanol and control experiments and the results did not differ significantly. The lowest hormone concentrations were observed 1-5 h after the start of infusion. Oestradiol, oestrone and oestrone-sulphate concentrations decreased 24-46% compared to basal values. 5 alpha-dihydro-testosterone levels decreased 23-31%, androstenedione and dehydroepiandrosterone-sulphate levels decreased 6-48%, while testosterone levels did not change significantly. Prolactin concentrations were reduced by 41-51% of basal values and luteinizing hormone concentrations by 37-68% Follicle stimulating hormone levels did not change significantly. Stress factors or haemodilution are not likely explanations of the observed changes in hormone concentrations. A circadian rhythm could not explain changes in hormones of non-adrenal origin.

Aminoglutethimide is effective in the treatment of breast cancer in postmenopausal patients as a result of its inhibition of aromatase. Its use is complicated by a number of endocrine side-effects which include the inhibition of thyroxine synthesis and inhibition of 11-steroid and 21-steroid hydroxylases. When aminoglutethimide is used at the conventional daily dose of 1000 mg in combination with 40 mg of hydrocortisone these effects can result in clinically significant hypothyroidism and increases in the serum levels of oestrone in response to stimulation of adrenocorticotropic hormone (ACTH). In the current study it was found that with twice daily treatment at the low dose of 125 mg aminoglutethimide plus 20 mg hydrocortisone there was no significant increase in oestrone levels after ACTH stimulation. In addition there was little effect on thyroid function: serum levels of triiodothyronine and thyroxine were unaffected whilst there was a marginally significant (P less than 0.05) increase in thyroid-levels were confined to those patients with pretreatment values greater than 2.5 mU/L, the most marked effect being in 1 patient whose pretreatment level was already outside the normal range.

The maternal recognition of pregnancy takes a number of forms in different species; among the eutherian mammals the maintenance of luteal function and cessation of oestrous or menstrual cycles is an important event in early pregnancy. In the pig the embryos signal their presence in the uterus between Days 10 and 12 post coitum; this time corresponds to the onset of blastocyst synthesis of oestrogens, which are luteotrophic in this species, and it has been suggested that oestrogens may constitute an embryonic signal responsible for maintained luteal function in pregnancy. Although oestrone sulphate, which is formed from oestrogens of embryonic origin by uterine sulphotransferase, has been found in the maternal circulation in high concentrations after Day 15 p.c., its appearance is late relative to the time of maternal recognition of pregnancy. Therefore an alternative mechanism has been sought. The recent finding that oestradiol is capable of reducing uterine prostaglandin F2 alpha secretion (i.e. acting as an antiluteolysin), and that it is present in uterine venous blood as early as Day 12 p.c. in pregnant pigs, suggests a mechanism whereby blastocyst oestrogens may be capable of influencing luteal function.

Conceptus (placental membranes, fetal fluids and fetus) development was characterized between Days 27 and 111 of gestation. Progestagens, oestrone, oestradiol, oestrone sulphate and prostaglandins (PG) F were measured in maternal plasma and allantoic and amniotic fluids. Protein concentrations are described for fetal fluids. The early increase in placental membrane weight from 1.12 g (27 days) to 58.45 g (50 days) was associated with oestrogen production presumably of conceptus origin. Oestrogens increased significantly in allantoic and amniotic fluids throughout the period studied with oestrone being the primary free oestrogen, rising from 2 pg/ml (Day 33) to 144 ng/ml by 111 days in allantoic fluid. Changes in plasma oestrogens of the maternal circulation were not detected until after Day 70 at which time oestrone concentration was greater than that of oestradiol. Fetal fluid concentrations of progestagens, oestrone sulphate and PGF were not related to maternal plasma levels and a sequestration of these hormones by the allantois is postulated.

A gonadotrophin-releasing hormone (GnRH) analogue, D-Ser[TBU]LRH-EA10, (GnRH-A), at a dose of 200 micrograms was given daily for 2 months to 6 women with polycystic ovarian disease (PCO). Prior to therapy the patients presented elevated LH, testosterone (T), oestrone (E1) and dihydrotestosterone (DHT) in the circulation. In response to GnRH-A, these subjects exhibited a marked decrease in circulating T, DHT and androstenedione (A) levels as measured 24 h after GnRH-A injection, by 4 weeks and onwards (P less than 0.05). After 2 weeks of daily administration, the serum LH profile, evaluated by sampling at 2, 4, 7 and 24 h after injection of GnRH-A, was not different from baseline, whereas after 4, 6 and 8 weeks the levels were significantly lower (*P less than 0.01). The profile of serum T levels was unmodified at the second week, but significantly decreased thereafter (*P less than 0.01). At the end of treatment, the E1 concentrations, elevated in pre-injection condition, were markedly decreased. These data demonstrate that in PCO subjects, GnRH-A significantly lowered the elevated levels of androgens commonly found in these patients. The close correlation observed between reduced serum LH and androgen concentrations suggests that pituitary desensitization could be responsible for the reduction in androgen levels, and may be evidence for a gonadotrophin dependence of the elevated concentrations of T in these patients.

Inhibition of steroid sulphatase is now an important target for the development of new drugs for the treatment of women with endocrine-dependent breast tumours. The first potent sulphatase inhibitor identified, oestrone-3-O-sulphamate (EMATE) proved. unexpectedly, to be oestrogenic. A number of strategies have therefore been adopted to design and synthesize a non-oestrogenic inhibitor. For this, a number of modifications have been made to the A and D rings of the oestrone nucleus. 2 Methoxyoestrone-3-O-sulphamate, while having similar in vitro and in vivo sulphatase inhibitory potency to that of EMATE, was devoid of oestrogenic activity when tested at 2 mg/kg in an ovariectomised rat uterine weight gain assay. 17-Deoxyoestrone-3-O-sulphamate was also a potent steroid sulphatase inhibitor and while it was devoid of oestrogenic activity when tested at 0.1 mg/kg, did stimulate uterine growth at 1.0 mg/kg. As an alternative approach to the use of steroid-based inhibitors a number of single ring, bicyclic non-fused ring, and two fused ring sulphamate analogues were designed, synthesized and tested for their ability to inhibit steroid sulphatase activity. In general, although the single ring and bicyclic non-fused ring sulphamate analogues could inhibit sulphatase activity, they were considerably less potent than EMATE. The mono- and bis-sulphamate derivatives of 5,7-dihydroxyisoflavone were relatively potent, inhibiting in vivo steroid sulphatase activity by 62 and 81% respectively at a single oral dose of 10 mg/kg. A study of the structure-activity relationship of a series of coumarin-based sulphamates has led to the development of a number of potent non-steroidal inhibitors, one of which has a similar potency to that of EMATE. The identification of potent steroid- and non-steroid-based sulphatase inhibitors will enable the therapeutic value of this therapy to be examined in the near future.

At menopause, several abnormalities in oestrogen metabolism have been reported, which may increase the likelihood of cancer development in the breast or uterus following oestrone or oestradiol-17 beta supplementation. Occult hypothyroidism reduces the rate of oestrogen inactivation by C2 hydroxylation, and 15-20% of women have low rates of C16 hydroxylation to oestriol. Reduced sex hormone binding globulin concentration occurs in association with obesity, thereby increasing the biologically active unbound fraction of oestradiol in plasma. Since oestriol undergoes minimal metabolism after absorption, does not bind to sex hormone binding globulin, and has an anti-oestradiol action by decreasing the duration of nuclear binding of oestradiol-receptor proteins, it is less likely to induce proliferative changes in target organs of cancer-prone women than oestrone or oestradiol. Intermittent non-conjugated oestriol treatment has demonstrated the most significant anti-mammary carcinogenic activity of 22 tested compounds as well as anti-uterotropic activity in intact female Sprague Dawley rats fed either of two dissimilar carcinogens (7, 12 dimethylbenz(a) anthracene, procarbazine) and followed for their natural life span. The protective effect was specific for mammary carcinomas only and has been decreased in rats with a 20% increase in growth curves. Clinical experience thus far with oral oestriol therapy of post-menopausal women has indicated little hazard of cancer development.

To increase the sample-handling capacity for an induction of ovulation programme, direct urinary radioimmunoassays (RIA) for three steroid glucuronides, pregnanediol-3-glucuronide (Pd-3-G), oestrone-3-glucuronide (E1-3-G), and oestriol-16 alpha-glucuronide (E3-16-G), were established. Results obtained for urinary Pd-3-G measured by direct RIA show an excellent correlation (r = 0.98, N = 46) with those for urinary pregnanediol measured by gas-liquid chromatography. Estrone-3-glucuronide (E1-3-G) and estriol-16 alpha-glucuronide (E3-16-G) values, measured by direct RIA, closely paralleled the total urinary oestrogen measured fluorimetrically. Ovarian response to ovulation induction therapy can be monitored by observing the changes in the levels of E1-3-G in urine. Pre-ovulatory levels of urinary E3-16-G were found to be too low for use in this regard. Direct RIA for E1-3-G and Pd-3-G are recommended as reliable indices of ovarian function in the monitoring of patients receiving treatment for the induction of ovulation.

Rat alpha-foetoprotein was separated into nine molecular variants by electrophoresis and affinity chromatography on Ricinus communis agglutinin and concanavalin-A. The nine variants are able to bind oestrone with the same capacity of one binding site per alpha-foetoprotein molecule. The association constants seem to vary with the sialic acid composition of the iso-alpha-foetoprotein.

The Velhas River is the most polluted river in the state of Minas Gerais, south-eastern Brazil. Due to its historical and environmental relevance, the aim of this study was to evaluate the effects of oestrogenic endocrine disruptors on the reproduction of the lambari Astyanax rivularis, a small-sized species found in headwaters of the São Francisco River basin. Quarterly field samplings were carried out during a reproductive cycle in three streams of the upper Velhas River: S1 (reference site) and S2 and S3 (sites contaminated by untreated sewage). The main oestrogenic compounds were evaluated in water using HPLC/MS. Molecular, histological and reproductive biomarkers were assessed in liver and gonad. The results showed higher average concentrations of oestradiol (>200ng/l) in S2 and S3, oestrone (>250ng/l) in S2 as well as oestriol (>200ng/l), bisphenol A (>190ng/l), and nonylphenol (>600ng/l) in S3 compared to S1 (<70ng/l for all compounds). In S2 and S3, there was an increase in the proportion of females, higher ELISA levels of vitellogenin (Vtg) and proteins of the zona radiata (Zrp) in liver males. Insulin-like growth factor (IGF-I) levels were lower in S2 males, which also had a smaller body size, a smaller seminiferous tubule diameter, a higher proportion of spermatogonia, and lower proportion of spermatozoa in relation to S1. Histopathological analyses detected an increase in yolk deficient oocytes and over-ripening in the contaminated sites, and these alterations were associated to a reduction of hepatic Vtg levels and a delay in spawning, respectively. Intersex specimens with perinucleolar follicles in a multifocal distribution in the testis were detected in S2 and S3. These results indicate that chronic exposure to oestrogenic compounds induced endocrine disruption that may affect wild populations of A. rivularis in the Velhas River.

The cerebellum is a steroidogenic organ that expresses steroidogenic enzymes and produces neurosteroids. Purkinje neurones appear to be the most active steroidogenic cells in the cerebellar cortex. These neurones express 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD), P450 side-chain cleavage (P450scc), 17 alpha-hydroxylase/c17, 20lyase (P450c17), P450 aromatase (P450arom) and produce pregnenolone, progesterone, dehydroepiandrosterone, androstenedion, oestradion and oestrone. Oligodendrocytes are predominantly the producer of myeline protein. The oligodendrocytes were identified by immunohistochemistry using a monoclonal antibody against myeline 2', 3'-cyclic nucleotide 3'-phosphodiesterase (CNPase), a myeline specific enzyme. In this study we have examined the distribution of 3 beta-HSD and CNPase by immunohistochemistry using monoclonal antibody in canine cerebellar cortex. The localization of oligodendrocytes within the cerebellar cortex was determined to be close to Purkinje neurones. This result suggests that endogenous progesterone synthesized de novo in the Purkinje neurone can promote myeline protein synthesis in oligodentrocytes.

Aromatase inhibitors and inactivators are playing an increasing greater role in breast cancer treatment. Exemestane, a highly specific, steroidal aromatase inactivator, is the newest agent in this class. The drug is highly specific, and inhibits the in vivo conversion of androstenedione to oestrone (aromatization) by a mean of 97.9%. Exemestane has shown good efficacy and tolerability in multiple clinical trials among patients with metastatic breast cancer who have failed one or more previous hormonal therapies. Exemestane 25 mg/day slows disease progression and reduces tumour-related signs and symptoms and the drug exhibits a partial lack of cross-resistance with the non-steroidal aromatase inhibitors. Response rates to exemestane of 14% to 29% were observed including patients with visceral metastases, who have historically proven difficult to treat. In a large phase III trial, exemestane was found to be superior to megestrol acetate with respect to time to progression and overall survival. In addition, exemestane is currently under investigation as first-line therapy in metastatic disease and in sequence with tamoxifen in the adjuvant setting. Adverse events include low-grade hot flashes, nausea, and fatigue--mostly of mild to moderate intensity--and treatment-related discontinuations are rare. In conclusion, exemestane represents a novel and interesting drug for the treatment of advanced breast cancer, with exciting prospects for use in adjuvant therapy and, potentially, breast cancer prevention.

The vaginal absorption of oestradiol was studied during maintenance therapy with low-dose oestradiol. Six women with severe vaginal atrophy due to oestrogen deficiency were treated with a vaginal tablet containing 25 micrograms 17 beta-oestradiol. Initially, a daily dose was given for 2 weeks, followed by maintenance therapy with twice weekly treatment for another 10 weeks. The plasma concentrations of unconjugated oestrone and oestradiol were measured before oestrogen treatment was started at the beginning of the study. After 3 months of treatment frequent plasma sampling over a period of 24 h was performed. Gonadotrophins, vaginal and urethral cytology, clinical findings and subjective symptoms were assessed at the beginning and end of the study. Plasma concentrations of unconjugated oestradiol were at all times within the limits of postmenopausal values, but showed a slight but not statistically significant elevation after 3 months compared to pretreatment values. Plasma concentrations of unconjugated oestrone were in the low postmenopausal range throughout the study. LH levels were unaffected during the study, while FSH was somewhat lowered, but still well within the postmenopausal range. Vaginal and urethral cytology showed maturation with almost complete disappearance of parabasal cells. Clinical and subjective improvement was statistically significant during the treatment period.

The effect of a low dose of mifepristone (RU486) on ovarian and endometrial function was studied in 14 healthy women. The study included one control and two treatment cycles. During the treatment cycles, either 2.5 mg (n = 9) or 5 mg (n = 5) of mifepristone was administered once weekly. The concentration of ovarian steroids and luteinizing hormone (LH) in urine was measured daily, cortisol in blood once weekly and glycodelin (placental protein 14; PP14) at the time of menstruation. Ovarian function was monitored by vaginal ultrasound. An endometrial biopsy was taken in each cycle in the mid-luteal phase, based on self-measurement of the LH peak, or on cycle day 22 if no LH peak could be detected. In the evaluation of the results, the outcome of the enzyme immunoassay of LH was used to date the biopsy. Endometrial progesterone and oestrogen receptors and Dolichus biflorus agglutinin (DBA) lectin binding were measured. Ovulation was not inhibited by treatment with mifepristone, and an LH peak could be determined in all control and treatment cycles. However, in four subjects (one with the higher and three with the lower dose) the follicular phase was prolonged by 6-13 days. The duration of the luteal phase and the concentrations of pregnanediol and oestrone glucuronide were not affected by treatment. A dose of 5 mg, and to a lesser extent 2.5 mg, mifepristone once weekly caused desynchronization of endometrial development. Endometrial progesterone receptor, but not oestrogen receptor, concentration was significantly increased by the higher dose. A significant reduction in DBA-lectin binding and in serum glycodelin concentrations was also found. Thus, low doses of mifepristone do not inhibit ovulation but delay endometrial development and impair secretory activity. Whether these effects are sufficient to prevent implantation remains to be established.

Oesterone, oestradiol-17 beta, progesterone and testosterone were measured by radioimmunoassay in daily plasma samples throughout the ovarian cycle in 4 female owl monkeys. Clearly defined peaks of oestradiol-17 beta occurred at intervals of 15.5 +/- 0.56 days and confirmed the length of the cycle reported previously. Progesterone rose on the day on the day of the oestradiol-17 beta to reach a maximum 4--6 days later, thereafter decreasing gradually to low levels before the onset of the next cycle. On the basis of these data the follicular and luteal phases were estimated to be 6 and 10 days respectively. Osterone and testosterone peaks preceded that of progesterone by 24 and remained elevated throughout the luteal phase. Plasma concentrations of all steroids were markedly higher than for other primate species. Vaginal cytology was considered unsuitable as an indicator of the stage of the ovarian cycle.

We previously reported that postmenopausal obese women exhibit increased levels of circulating adipocyte fatty acid binding protein (A-FABP), which is associated with breast cancer (BC) development. In postmenopause, increased oestrogen levels are reported to be associated with increased BC risk. Herein, we assessed if oestrogens, including oestrone (E1), oestradiol (E2) and oestriol (E3), are associated with A-FABP in the obesity-related BC development. We collected 249 serum samples from women with or without BC and measured serum levels of E1, E2, E3 and A-FABP. Considering all subjects, E1 and E2 but not E3 levels were significantly higher in pre- than in postmenopause individuals. E3 and E1 levels were higher in non-obese than in obese women. When samples were separated by BC status, E2 levels were significantly higher, while E1 and E3 levels were significantly lower in postmenopausal obese than non-obese women without BC. These differences based on body mass index (BMI) were not observed among women with BC. E3 levels were higher in obese women with BC than those without. A-FABP levels were significantly higher in postmenopausal obese women regardless of BC status. In addition, A-FABP was not associated with E1, E2 or E3. Altogether, our data suggest that A-FABP is independently regulated by obesity and menopausal status compared to oestrogens, thus playing a unique role in the development of BC.

Serum concentrations of oestrone, oestradiol, follicle-stimulating hormone (FSH), luteinizing hormone (LH), and sex hormone-binding globulin (SHBG) were significantly (P less than 0.01) raised in men with alcoholic liver cirrhosis (no. = 42) compared with age-matched controls (no. = 20). No significant difference was observed when comparing serum testosterone concentrations. Patients were divided into three groups in accordance with the severity of liver cirrhosis, using biochemical and clinical criteria. Patients with the best-preserved liver function (no. = 11) and patients with moderately affected liver function (no. = 18) had significantly (P less than 0.05) raised serum concentrations of testosterone, FSH, and LH when compared with both controls and patients with severely affected liver function (no. = 13). Serum concentrations of testosterone, FSH, and LH in the latter group showed no significant differences from the controls. Serum concentrations of oestrone and oestradiol were significantly (P less than 0.05) increased in all patient groups, and serum oestrone increased with decreasing liver function. No significant differences were observed concerning SHBG concentrations in the three groups of patients. Dexamethasone suppression did not change the concentration of testosterone significantly, but oestrone and oestradiol concentrations decreased significantly (P less than 0.01) in controls and patients. In patients, but not in controls, a significant (P less than 0.01) increase in FSH and LH concentrations was observed after dexamethasone suppression. The mean percentage increase of FSH and LH was higher the greater the severity of liver cirrhosis.

Steroids play an important role in mammalian reproduction and early pregnancy. Although systemic changes in steroid concentrations have been well documented, it is not clear how these correlate with local steroid concentrations in the genital tract. We hypothesised that, in the horse, the preimplantation embryo may be subjected to high local steroid concentrations for several days. Therefore, we measured progesterone, 17-hydroxyprogesterone, 17?-oestradiol, testosterone and 17?-testosterone concentrations in equine oviductal tissue by ultra-HPLC coupled with tandem mass spectrometry, and progesterone, 17?-oestradiol, oestrone and testosterone concentrations in oviduct fluid by radioimmunoassay, with reference to cycle stage and side of ovulation. Progesterone concentrations were high in oviductal tissue and fluid ipsilateral to the ovulation side during dioestrus, whereas other steroid hormone concentrations were not influenced by the side of ovulation. These results suggest that the high ipsilateral progesterone concentration is caused by: (1) contributions from the follicular fluid in the oviduct and diffusion of follicular fluid steroids after ovulation; (2) local transfer of steroids via blood or lymph; (3) local synthesis of progesterone in the oviduct, as evidenced by the expression of steroidogenic enzymes; and (4) a paracrine contribution from follicular cells. These data provide a basis for the study of the importance of endocrine and paracrine signalling during early embryonic development in the horse.

Cirrhosis is associated with hormonal dysregulation, as evidenced by secondary amenorrhoea in reproductive-aged women, and feminization of cirrhotic men. Whether hormone levels vary by severity of cirrhosis in women is not known. If identified, such changes may have important clinical relevance, particularly, as low sex hormone binding globulin (SHBG) and follicle stimulating hormone (FSH) are known to promote metabolic and cardiovascular disease in women. In a cohort of post-menopausal women with chronic hepatitis C virus (HCV) infection, we compared comprehensive sex hormone levels by presence of cirrhosis, as well as across Child-Turcotte-Pugh (CTP) class. Results: There were n = 18 cirrhotic and n = 21 noncirrhotic women with a median age of 57 years (interquartile range [IQR] 53-62). Compared to noncirrhotics, cirrhotic women had higher oestradiol (11.0 vs 6.0 pg/mL, P = 0.05) and oestrone levels (32.0 vs 8.0 ng/mL, P < 0.001), and lower sex hormone binding globulin (SHBG) (69.2 vs 155.6 nmol/L, P = 0.001), and FSH levels (4.9 vs 89.6 mIU/mL, P < 0.001). Among cirrhotic women, there was a progressive decline in FSH and SHBG and concurrent rise in oestrone levels from CTP class A to C (test of trend, P values ≤0.02). Cirrhosis is associated with lower FSH and SHBG levels in cirrhotic compared to noncirrhotic women with HCV infection. In cirrhotic women, these levels demonstrate steady decline by disease severity. Given known associations of low SHBG and FSH with cardio-metabolic disease, the clinical implications of hormonal changes by cirrhosis severity in HCV-infected women warrants investigation.

Steroidal oestrogens are often accumulated in urban estuarine sediments worldwide at microgram per gram levels. These aromatic steroids have been classified as endocrine disruptors and group 1 carcinogens. Microbial degradation is a naturally occurring mechanism that mineralizes oestrogens in the biosphere; however, the corresponding genes in oestrogen-degrading actinobacteria remain unidentified. In this study, we identified a gene cluster encoding several putative oestrogen-degrading genes (aed; actinobacterial oestrogen degradation) in actinobacterium Rhodococcus sp. strain B50. Among them, the aedA and aedB genes involved in oestrogenic A-ring cleavage were identified through gene-disruption experiments. We demonstrated that actinobacterial oestrone 4-hydroxylase (AedA) is a cytochrome P450-type monooxygenase. We also detected the accumulation of two extracellular oestrogenic metabolites, including pyridinestrone acid (PEA) and 3aα-H-4α(3'-propanoate)-7aβ-methylhexahydro-1,5-indanedione (HIP), in the oestrone-fed strain B50 cultures. Since actinobacterial aedB and proteobacterial edcB shared < 40% sequence identity, 4-hydroxyestrone 4,5-dioxygenase genes (namely aedB and edcB) could serve as a specific biomarker to differentiate the contribution of actinobacteria and proteobacteria in environmental oestrogen degradation. Therefore, 4-hydroxyestrone 4,5-dioxygenase genes and the extracellular metabolites PEA and HIP were used as biomarkers to investigate oestrogen biodegradation in an urban estuarine sediment. Interestingly, our data suggested that actinobacteria are active oestrogen degraders in the urban estuarine sediment.

The purpose of this study was to determine how oophorectomy and different hormone replacement therapy (HRT) regimens using low doses of medroxyprogesterone acetate (MPA, 2.5 mg/day) influence the pituitary-gonadal axis function. Ninety (90) women, who had had regular menses prior to surgery, completed a 1-year follow-up period. Patients were assigned to 5 groups. The first (n = 16) received 0.625 mg/day conjugated equine oestrogens (CEE) cyclically, the second (n = 20) 50 micrograms day transdermal oestradiol (E2) cyclically and the third (n = 15) 0.625 mg/day CEE continuously. These 3 groups also received 2.5 mg MPA sequentially for the last 12 days of HRT administration. The fourth group (n = 20) received 0.625 mg/day CEE and 2.5 mg/day of MPA continuously, while the fifth (n = 19) constituted a control group. After oophorectomy all patients showed increases in follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels, and decreases in those of E2, oestrone (E1), prolactin (PRL), sex-hormone-binding globulin (SHBG), androstenedione (delta A4) and testosterone (T). No changes were detected in dehydroepiandrosterone sulphate (DHEA-S) levels. After HRT, decreases in FSH, LH and PRL levels and increases in those of E2, E1 and SHBG were observed, but no changes were seen in T, delta A4 or DHEA-S plasma levels. As the differences that were found cannot be attributed to the presence of ovaries, it is reasonable to assume that they were perhaps due to the treatment. All these changes, with the exception of a decrease in PRL levels, are therefore to be expected after HRT.

The endometrium of pregnant and cyclic pigs is a source of oestrone (E1) and 17β-oestradiol (E2). However, the roles of LH, FSH and prolactin (PRL) as regulators of endometrial steroidogenesis, and the presence of 17β-hydroxysteroid dehydrogenase (17β-HSD) in the porcine endometrium, remain unknown. Therefore, in the present study we examined 17β-HSD expression and the effects of LH, FSH and PRL on E1 and E2 release in vitro in endometrial explants harvested from gravid pigs on Days 10-11 (embryo migration within the uterus), 12-13 (maternal recognition of pregnancy) and 15-16 (beginning of implantation) and compared them with results obtained in non-gravid pigs. The results show that: (1) endometrial 17β-HSD activity was decreased on Days 15-16 in pregnant and cyclic pigs compared with the preceding days; (2) LH, FSH and PRL increased endometrial E1 secretion on Days 10-11 and 15-16 of pregnancy and on Days 12-13 and 15-16 of the oestrous cycle; and (3) LH, FSH and PRL increased endometrial E2 secretion on Days 15-16 of pregnancy and during the days studied in the oestrous cycle. In conclusion, data suggest that LH, FSH and PRL affect endometrial secretion of estrogens in pigs.