High Estrogen Concentrations Research Articles

Association of serum leptin with serum estradiol in relation to breast carcinogenesis: a comparative case-control study between pre- and postmenopausal women

Background/aim: The aims of this study were to observe the interhormonal relationship of serum leptin with serum estradiol and to compare pre- and postmenopausal women for possible implications in breast carcinogenesis. Materials and methods: This comparative case-control study encompasses 175 breast cancer patients and 175 age-, sex-, and BMI- matched healthy controls. For comparison, the subjects were divided into pre- and postmenopausal groups according to their menstrual history. Blood samples were analyzed for serum leptin and serum estradiol by the ELISA method. Results: Higher mean values of serum estrogen and leptin were observed in breast cancer cases among both the pre- and postmenopausal groups. While estimating the association of serum leptin with serum estradiol, a weak positive (r = 0.186) but statistically significant (P = 0.022) correlation was found among the premenopausal subjects, while a moderate positive association (r = 0.556) was found among the postmenopausal subjects, which had high statistical significance (P = 0.001). Furthermore, correlation coefficients (r) of the pre- and postmenopausal groups were compared using Fisher r-to-z transformation and found to have a statistically significant difference (z = 4.03, P = 0.0001). Conclusion: The findings of this study suggest the mitogenic effects of leptin on mammary tissue via augmenting peripheral estrogen production more significantly among postmenopausal subjects. Thus, the therapeutic modulation of leptin may be a potential adjuvant treatment for breast cancer patients with high levels of leptin along with high estrogen concentration as a consequence.

Determinação de hormônios estrogênicos em esgoto bruto e efluente de uma estação descentralizada de tratamento por lodos ativados

Hormônios estrogênicos, provenientes dos esgotos, atingem os corpos hídricos e podem causar perturbações aos organismos aquáticos. Os tratamentos secundários das estações de tratamento de esgoto (ETE) possibilitam alguma remoção destes compostos, mesmo em ETEs descentralizadas, apesar de ainda haver poucos estudos sobre elas. Em sistemas por lodos ativados, a eficiência tem sido relacionada ao tempo de detenção hidráulica (TDH), à idade de lodo, à desnitrificação biológica e à carga de alimentação. O objetivo deste trabalho foi quantificar os hormônios estrona (E1), 17-β-estradiol (E2), estriol (E3) e 17-α-etinilestradiol (EE2) no esgoto e no efluente de uma ETE descentralizada por lodos ativados, além de caracterizar a ETE do Campus Universitário da EEL-USP quanto à matéria orgânica recebida, ao tempo de detenção hidráulica e a remoção de nitrogênio. Cromatografia líquida com detecção UV foi utilizada na determinação dos hormônios. Os resultados mostraram concentrações dos hormônios superiores às encontradas na literatura, em ambos: esgoto (5,158 ± 2,747; 7,434 ± 4,356; 5,200 ± 3,331 e 5,638 ± 4,312 μg L-1 de E1, E2, E3 e EE2) e efluente (5,062 ± 3,366; 4,191 ± 3,527; 7,743 ± 3,951, 2,550± 2,162 de E1, E2, E3 e EE2). No esgoto, as altas concentrações podem ser relacionadas à maior predominância de urina, visto os altos níveis de nitrogênio detectados, à menor geração de esgoto e a amostragem em período seco causando reduzida diluição dos hormônios. Remoção insuficiente dos hormônios devido a menor TDH (2h05) e irregularidade na desnitrificação (-54 a 61%) pode ser o motivo das altas concentrações de estrógenos no efluente. Ademais, a desconjugação dos hormônios pode ter ocorrido durante o tratamento.

SULFATION PATHWAYS: Formation and hydrolysis of sulfonated estrogens in the porcine testis and epididymis.

Boars exhibit high concentrations of sulfonated estrogens (SE) mainly originating from the testicular-epididymal compartment. Intriguingly, in porcine Leydig cells, sulfonation of estrogens is colocalized with aromatase and steroid sulfatase (STS), indicating that de novo synthesis of unconjugated estrogens (UE), their sulfonation and hydrolysis of SE occur within the same cell type. So far in boars no plausible concept concerning the role of SE has been put forward. To obtain new information on SE formation and hydrolysis, the porcine testicular-epididymal compartment was screened for the expression of the estrogen-specific sulfotransferase SULT1E1 and STS applying real-time RT-qPCR, Western blot and immunohistochemistry. The epididymal head was identified as the major site of SULT1E1 expression, whereas in the testis, it was virtually undetectable. However, SE tissue concentrations are clearly consistent with the testis as the predominant site of estrogen sulfonation. Results from measurements of estrogen sulfotransferase activity indicate that in the epididymis, SULT1E1 is the relevant enzyme, whereas in the testis, estrogens are sulfonated by a different sulfotransferase with a considerably lower affinity. STS expression and activity was high in the testis (Leydig cells, rete testis epithelium) but also present throughout the epididymis. In the epididymis, SULT1E1 and STS were colocalized in the ductal epithelium, and there was evidence for their apocrine secretion into the ductal lumen. The results suggest that in porcine Leydig cells, SE may be produced as a reservoir to support the levels of bioactive UE via the sulfatase pathway during periods of low activity of the pulsatile testicular steroidogenesis.

Modulation of HIV replication in monocyte derived macrophages (MDM) by steroid hormones.

Significant sex specific differences in the progression of HIV/AIDS have been reported. Several studies have implicated steroid hormones in regulating host factor expression and modulating HIV transmission and replication. However, the exact mechanism exerted by steroid hormones estrogen and progesterone in the regulation of HIV-1 replication is still unclear. Results from the current study indicated a dose dependent down regulation of HIV-1 replication in monocyte derived macrophages pre-treated with high concentrations of estrogen or progesterone. To elucidate the molecular mechanisms associated with the down regulation of HIV-1 replication by estrogen and progesterone we used PCR arrays to analyze the expression profile of host genes involved in antiviral responses. Several chemokines, cytokines, transcription factors, interferon stimulated genes and genes involved in type-1 interferon signaling were down regulated in cells infected with HIV-1 pre-treated with high concentrations of estrogen or progesterone compared to untreated HIV-1 infected cells or HIV-1 infected cells treated with low concentrations of estrogen or progesterone. The down regulation of CXCL9, CXCL10 and CXCL11 chemokines and IL-1β, IL-6 cytokines in response to high concentrations of estrogen and progesterone pre-treatment in HIV-1 infected cells was confirmed at the protein level by quantitating chemokine and cytokine concentrations in the culture supernatant. These results demonstrate that a potent anti-inflammatory response is mediated by pre-treatment with high concentrations of estrogen and progesterone. Thus, our study suggests a strong correlation between the down-modulation of anti-viral and pro-inflammatory responses mediated by estrogen and progesterone pre-treatment and the down regulation of HIV-1 replication. These findings may be relevant to clinical observations of sex specific differences in patient populations and point to the need for further investigation.

Circulating sex hormones in relation to anthropometric, sociodemographic and behavioural factors in an international dataset of 12,300 men.

IntroductionSex hormones have been implicated in the etiology of a number of diseases. To better understand disease etiology and the mechanisms of disease-risk factor associations, this analysis aimed to investigate the associations of anthropometric, sociodemographic and behavioural factors with a range of circulating sex hormones and sex hormone-binding globulin.MethodsStatistical analyses of individual participant data from 12,330 male controls aged 25–85 years from 25 studies involved in the Endogenous Hormones Nutritional Biomarkers and Prostate Cancer Collaborative Group. Analysis of variance was used to estimate geometric means adjusted for study and relevant covariates.ResultsOlder age was associated with higher concentrations of sex hormone-binding globulin and dihydrotestosterone and lower concentrations of dehydroepiandrosterone sulfate, free testosterone, androstenedione, androstanediol glucuronide and free estradiol. Higher body mass index was associated with higher concentrations of free estradiol, androstanediol glucuronide, estradiol and estrone and lower concentrations of dihydrotestosterone, testosterone, sex hormone-binding globulin, free testosterone, androstenedione and dehydroepiandrosterone sulfate. Taller height was associated with lower concentrations of androstenedione, testosterone, free testosterone and sex hormone-binding globulin and higher concentrations of androstanediol glucuronide. Current smoking was associated with higher concentrations of androstenedione, sex hormone-binding globulin and testosterone. Alcohol consumption was associated with higher concentrations of dehydroepiandrosterone sulfate, androstenedione and androstanediol glucuronide. East Asians had lower concentrations of androstanediol glucuronide and African Americans had higher concentrations of estrogens. Education and marital status were modestly associated with a small number of hormones.ConclusionCirculating sex hormones in men are strongly associated with age and body mass index, and to a lesser extent with smoking status and alcohol consumption.

17β-estradiol reduces Cav 1.2 channel abundance and attenuates Ca2+ -dependent contractions in coronary arteries.

One mechanism by which the female sex may protect against elevated coronary vascular tone is inhibition of Ca2+ entry into arterial smooth muscle cells (ASMCs). In vitro findings confirm that high estrogen concentrations directly inhibit voltage‐dependent Cav1.2 channels in coronary ASMCs. For this study, we hypothesized that the nonacute, in vitro exposure of coronary arteries to a low concentration of 17β‐estradiol (17βE) reduces the expression of Cav1.2 channel proteins in coronary ASMCs. Segments of the right coronary artery obtained from sexually mature female pigs were mounted for isometric tension recording. As expected, our results indicate that high concentrations (≥10 μmol/L) of 17βE acutely attenuated Ca2+‐dependent contractions to depolarizing KCl stimuli. Interestingly, culturing coronary arteries for 24 h in a 10,000‐fold lower concentration (1 nmol/L) of 17βE also attenuated KCl‐induced contractions and reduced the contractile response to the Cav1.2 agonist, FPL64176, by 50%. Western blots revealed that 1 nmol/L 17βE decreased protein expression of the pore‐forming α 1C subunit (Cav α) of the Cav1.2 channel by 35%; this response did not depend on an intact endothelium. The 17βE‐induced loss of Cav α protein in coronary arteries was prevented by the estrogen ER α/ER β antagonist, ICI 182,780, whereas the GPER antagonist, G15, did not prevent it. There was no effect of 1 nmol/L 17βE on Cav α transcript expression. We conclude that 17βE reduces Cav1.2 channel abundance in isolated coronary arteries by a posttranscriptional process. This unrecognized effect of estrogen may confer physiological protection against the development of abnormal Ca2+‐dependent coronary vascular tone.

High and low concentration of 17α-estradiol protect cerebellar granule neurons in different time windows

17α-estradiol is a hormonally inactive isomer of 17β-estradiol, but with similar potency as neuroprotector. However, we have previously reported that pretreatment with high concentration (10 μM) of both estrogens abolishes their neuroprotection in rat cerebellar granule neurons. Here, we have examined neuroprotective properties of 17α-estradiol against glutamate-induced excitotoxicity in chicken cerebellar granule neurons using low (1 nM) and high concentration.17α-Estradiol, 1 nM, was neuroprotective when glutamate was administered after a pretreatment period of 24 h, but not when coadministered with glutamate. In contrast, 10 μM was protective when coadministered with glutamate, but was not efficient when glutamate was administered after a pretreatment period. The difference in protection was linked to a stronger calcium response during glutamate exposure in the non-protective treatments. In addition, the pretreatment period with 10 μM was accompanied by increased protein level of the N-methyl-d-aspartate receptor subunit NR2B and reduced glutathione level. Thus, 17α-estradiol has a concentration and time dependent protective effect against glutamate-induced cell death.

Abnormal pregnancies associated with deviation in progestin and estrogen profiles in late pregnant mares: A diagnostic aid

Measurement of progestines and estrogens in maternal plasma has been advocated as an indicator of foeto-placental function. The goals of the present study were as follows: to determine progestin and estrogen concentrations in mares with normal and abnormal pregnancies during late gestation, evaluate the diagnostic value of hormone concentrations, and investigate the relationship between hormone concentrations after treatment and the survival of foals. Blood samples were collected monthly from 459 pregnant mares between Day 201 of gestation and foaling. Progestin and estrogen concentrations were measured using a time-resolved fluoroimmunoassay with anti-progesterone and anti-17β-estradiol antibodies. The cutoff values of hormone concentrations that best discriminated between healthy foals and foal loss groups were determined using receiver-operating characteristic (ROC) curve analysis. Mares with compromised pregnancies are treated with progestins, tocolytics and antibiotics according to clinical signs, ultrasonographic examination and hormonal test. We investigated the relationship between the restoration of hormone concentrations after treatment and the survival rate of the foals of 62 compromised mares. Maternal serum progestin and estrogen concentrations on Days 241–320 of gestation differed significantly between healthy foals and foal loss of each group. Predictions of pregnancy outcomes were based on ROC curve analysis that established cutoff values of serum progestin and estrogen concentrations for each 20-day interval during gestation. All mares with improved concentrations of progestins or estrogens after treatment delivered healthy foals. When hormone concentrations got worse after treatment, the rate of loss was higher when treatment was administered during Days 201–290 of gestation than after Day 290. Mares with high progestin and low estrogen concentrations were likely to deliver aborted/dead foals during mid-to-late gestation. These results suggest that measurement of progestin and estrogen concentrations may be useful for diagnosing abnormal pregnancy and implementing early treatment strategies.

Calcium and bone metabolism across women's life stages. The effects of oral contraceptives/low dose estrogen-progestin on bone metabolism, bone mass and geometry in adolescent and young adult women.

Estrogens have a biphasic action on pubertal and/or adolescent skeletal growth. Low levels of estrogen may increase the periosteal expansion through the increase in the sensitivity of bone for mechanical stimuli and the secretion of IGF-1. On the other hand, high estrogen concentrations may inhibit periosteal bone formation. To use OC/LEP(oral contraceptive/low dose estrogen-progestin) during adolescence, meaning exposure to high levels of estrogen, may prevent the acquisition of physiologic peak of bone mass.

Endometriosis and Ovarian Cancer: an Integrative Review (Endometriosis and Ovarian Cancer)

Despite being initially considered a benign disease, it is widely thought nowadays that endometriosis and especially ovarian endometriomas are neoplastic conditions with the potential to become malignant. This review was conducted to summarize, in a concise and systematic manner, the available scientific data relating endometriosis to ovarian cancer, published in the past five years. After reading abstracts and applying our predefined inclusion and exclusion criteria, a final list of 11 scientific papers was obtained and subjected to review. Endometriosis is associated with an increased risk of developing epithelial ovarian cancer (EOC), mainly of endometrioid and clear cell subtypes. This might be by virtue of the high estrogen concentration with the disease, which leads to malignant proliferation of endometriotic cysts, or be due to mutations in the ARID1A gene and consequent loss of BAF250a expression. The iron produced in the fluid of endometriotic cysts promotes oxidative stress, which in turn may cause genetic mutations and malignant progression of ovarian cysts.

Synchronous Multiple Lung Adenocarcinomas: Estrogen Concentration in Peripheral Lung.

BackgroundThe detection rate of synchronous multiple lung adenocarcinomas (SMLA), which display multiple ground glass opacity nodules in the peripheral lung, is increasing due to advances in high resolution computed tomography. The backgrounds of multicentric development of adenocarcinoma are unknown. In this study, we quantitated estrogen concentration in the peripheral lungs of postmenopausal female patients with SMLA.MethodsThe tissue concentration of estrogens (estrone [E1] and estdadiol [E2]) in the noncancerous peripheral lung were measured with liquid chromatography/electrospray tandem mass spectrometry in postmenopausal female patients with lung adenocarcinoma. The expression levels of CYP19A1 in the normal lung were also quantitated with real-time PCR. Thirty patients with SMLA and 79 cases of control patients with single lung adenocarcinoma were analyzed.ResultsThe concentrations of E1 and E2 in the noncancerous tissue were significantly higher in SMLA cases than control cases (P = 0.004 and P = 0.02, respectively). The minor allele (A) of single nucleotide polymorphism rs3764221 were significantly associated with higher concentration of E1 and E2 (P = 0.002 and P = 0.01, respectively) and higher CYP19A1 mRNA expression (P = 0.03).ConclusionThe tissue estrogen concentration of peripheral lung was significantly higher in SMLA than control cases. The high concentration of estrogen may be one of the causes of multicentric development of peripheral lung adenocarcinomas.

Bioaugmentation Mitigates the Impact of Estrogen on Coliform-Grazing Protozoa in Slow Sand Filters.

Exposure to endocrine-disrupting chemicals (EDCs), such as estrogens, is a growing issue for human and animal health as they have been shown to cause reproductive and developmental abnormalities in wildlife and plants and have been linked to male infertility disorders in humans. Intensive farming and weather events, such as storms, flash flooding, and landslides, contribute estrogen to waterways used to supply drinking water. This paper explores the impact of estrogen exposure on the performance of slow sand filters (SSFs) used for water treatment. The feasibility and efficacy of SSF bioaugmentation with estrogen-degrading bacteria was also investigated, to determine whether removal of natural estrogens (estrone, estradiol, and estriol) and overall SSF performance for drinking water treatment could be improved. Strains for SSF augmentation were isolated from full-scale, municipal SSFs so as to optimize survival in the laboratory-scale SSFs used. Concentrations of the natural estrogens, determined by gas chromatography coupled with mass spectrometry (GC-MS), revealed augmented SSFs reduced the overall estrogenic potency of the supplied water by 25% on average and removed significantly more estrone and estradiol than nonaugmented filters. A negative correlation was found between coliform removal and estrogen concentration in nonaugmented filters. This was due to the toxic inhibition of protozoa, indicating that high estrogen concentrations can have functional implications for SSFs (such as impairing coliform removal). Consequently, we suggest that high estrogen concentrations could impact significantly on water quality production and, in particular, on pathogen removal in biological water filters.

Cervical mucus characteristics and hormonal status at insemination of Holstein cows.

The present study was carried out to characterize the cervical mucus (CM) collected when inseminating Holstein cows and to relate the secretion pattern with pregnancy. The mucus was collected from mid-cervix of 64 cows with spontaneus estrus (SE) and induced estrus (IE). The quantity, pattern and consistency of the mucus, pH, arborization patterns and the sperm motility were observed. The levels of progesterone and estradiol 17β in serum were also determined. Pregnancy detection was performed by means of transrectal ultrasonography 60 days after insemination. Mucous secretion of cows with SE was significantly different from those with IE, showing a lower degree of crystallization (SE 2.00; IE 2.75) and a lower level of steroid hormones (P4: SE 0.17 ng/ml and IE 0.33 ng/ml (t 1.99547 α 0.05); E2: SE 30.95 pg/ml and IE 47.76 pg/ml (t 1.99495 α 0.05). Progesterone level was significantly lower and estrogen significantly higher in pregnant cows (P) in relation to that observed in non pregnant females (N) (P4: P 0.20 ng/ml and N 0.44 ng/ml (t 1.99602 α 0.05); E2: P 54.77 pg/ml and N 40.75 pg/ml (t 1.99505 α 0.05). In conclusion pregnancy was associated with acopious, clear and watery discharge (similar to egg white), with an arborization degree of 2.25, presence of atypical fern leaves together with rosette formations and needles or thorns on rails due to low levels of progesterone accompanied by high concentrations of estrogens.

Sex Hormones and Tendon.

The risk of overuse and traumatic tendon and ligament injuries differ between women and men. Part of this gender difference in injury risk is probably explained by sex hormonal differences which are specifically distinct during the sexual maturation in the teenage years and during young adulthood. The effects of the separate sex hormones are not fully elucidated. However, in women, the presence of estrogen in contrast to very low estrogen levels may be beneficial during regular loading of the tissue or during recovering after an injury, as estrogen can enhance tendon collagen synthesis rate. Yet, in active young female athletes, physiological high concentration of estrogen may enhance the risk of injuries due to reduced fibrillar crosslinking and enhanced joint laxity. In men, testosterone can enhance tendon stiffness due to an enhanced tendon collagen turnover and collagen content, but testosterone has also been linked to a reduced responsiveness to relaxin. The present chapter will focus on sex difference in tendon injury risk, tendon morphology and tendon collagen turnover, but also on the specific effects of estrogen and androgens.

Response of potassium channels to estrogen and progesterone in the uterine smooth muscle cells of adenomyosis in vitro

To investigate the expression of potassium channels and the influence of estrogen and progesterone on the cultured uterine smooth muscle cells (USMC) of adenomyosis in vitro. There were 22 cases of adenomyosis hysterectomy in the adenomyosis group and 12 patients with cervical intraepithelial neoplasia III removal of the uterus in the control group. USMC were separated and cultured in vitro, incubated with different concentrations of estrogen and progesterone. We used reverse transcription-PCR to dectect the expression of large-conductance calcium- and voltage-sensitive potassium channel α subunit (BKCa α) and voltage-gated potassium channel 4.3 (Kv4.3). The mRNA expression of BKCa α and Kv4.3 in the adenomyosis group (4.43±2.05 and 4.52±1.97) were significantly higher than those in the control group (0.83±0.25 and 0.86±0.19, P<0.05). In the control group, Kv4.3 mRNA decreased after treated with 0.1 nmol/L (0.17±0.10) and 1.0 nmol/L (0.13±0.08) estrogen than before (0.55±0.29, P<0.05). In the adenomyosis group, BKCa α mRNA decreased significantly after treated with 10.0 nmol/L estrogen (0.56±0.27 versus 1.01±0.35, P<0.05). 0.1 µmol/L progesterone elevated both BKCa α mRNA (0.44±0.24 versus 0.16±0.09) and Kv4.3 mRNA (1.29±0.51 versus 0.55±0.29) in the control group (all P<0.05); however, there were no significant difference in adenomyosis group of different concentration of progestrone (P>0.05). There is an abnormal expression of potassium channels in the adenomyosis USMC, which is regulated by high concentration of estrogen and might be resistant to progesterone.

Comparative analysis of intraluteal steroidogenic enzymes emphasises the functionality of fresh and persistent corpora lutea during pro—and metoestrus in the lynx

European lynx species demonstrate an atypical ovarian cycle compared to other felids. The physiological persistence of corpora lutea (CLs), reflected in constantly elevated progesterone (P4) concentrations in serum, is thought to ensure a seasonal monooestrus. Moreover, the coexistence of CLs from a recent ovulation (freshCLs) and persistent CLs from previous years (perCLs) on the same ovary has been proven. We assume that perCLs in lynxes occur due to fundamentally different mechanisms of luteal regression. Our study presents a detailed analysis of steroidogenic enzymes and steroids in fresh and perCLs obtained from Iberian lynxes during metoestrus, and in perCLs obtained from Eurasian lynxes during prooestrus. By quantitative PCR we measured relative mRNA amounts of steroidogenic acute regulatory protein (STAR), cytochrome P450 oxidases (CYPs), hydroxysteroid dehydrogenases (HSDs) and a steroid reductase (SRD). Protein expression in CLs was investigated for CYP11A1, CYP17A1, CYP19A1 and HSD3B. Additionally, the intraluteal and serum steroid content was determined. During metoestrus, mRNA amounts of STAR, CYP11A1, CYP19A1, HSD17B7 and SRD5A1 were significantly higher in perCLs compared to freshCLs. Protein of CYP11A1 was detected independently of the CL age in metoestrus, but expression was less evident in prooestrous perCLs. The protein signal of CYP17A1 was strong in freshCLs and perCLs of metoestrus, but weak at prooestrus. The presence of CYP19A1 protein was confirmed in each stage of the CL. These findings contribute to the hypothesis that CLs from previous years might support freshly developed CLs for pregnancy maintenance. However, initiation of ovulation might require a functional down-regulation of perCLs prior to breeding. It is noteworthy that the HSD3B1 mRNA amount was significantly elevated in fresh compared to perCLs (metoestrus). Accordingly, HSD3B protein was substantially present in freshCLs, whereas signals were literally absent in all perCLs. Elevated expression of HSD3B coincided with high intraluteal oestrogen concentrations in freshCLs; however, the enzyme pattern was less concordant with intraluteal P4 and androgen concentrations. Serum P4 concentrations of Iberian lynxes were constant between prooestrus and prolonged dioestrus. Moreover, constantly high serum oestrogen concentrations were measured during pro-, met- and prolonged dioestrus. The physiology of exceptionally high serum oestrogen concentrations outside the breeding season of lynxes merits further investigation. In conclusion our study supports the concept that the unique reproductive strategy of lynxes is directly linked to sustained intraluteal steroid biogenesis in persistent CLs.

The potential perinatal origin of placentation disorders in the young primigravida

The fetus is exposed to high plasma concentrations of unbound estrogens and progesterone throughout pregnancy. However, secretory or decidual changes in the fetal uterus occur relatively infrequently before birth, suggesting a variable endometrial progesterone response at the time of birth. Arguably, partial progesterone resistance that persists into adolescent years may compromise the physiological transformation of the spiral arteries and predispose for defective placentation in the case of pregnancy. Decidualization of the endometrial stromal compartment and junctional zone myometrium precedes trophoblast invasion. It represents the first step in the process of spiral artery remodeling needed to establish effective uteroplacental blood flow by midpregnancy. The major obstetric syndromes caused by impaired placental bed spiral artery remodeling are prevalent in teenage pregnancies, including preeclampsia, fetal growth restriction, and spontaneous preterm labor. Preconditioning of the uterus in response to cyclic menstruation during adolescence may be critical to achieve full uterine responsiveness to hormonal cues. Understanding the mechanisms of functional maturation of the uterus during the early reproductive years may yield novel insights into the major obstetric syndromes.

PO360 IS PROSTATIC SERUM ANTIGEN CORRELATED WITH INSULIN RESISTANCE IN MEN WITH TYPE 2 DIABETES MELLITUS-METS

Background: Metabolic syndrome (MetS) is a cluster of cardiovascular risk factors that includes hypertension, diabetes mellitus, obesity, hypertriglyceridemia, and low high-density lipoprotein cholesterol, with insulin resistance as the underlying hallmark feature. The prevalence of MetS has been increasing worldwide and has become a major public health problem in many western countries. Recently, increasing evidences suggests that MetS may be involved in the development and progression of certain types of cancer as an independent etiologic factor including breast cancer, endometrial cancer, colorectal cancer, pancreatic cancer and prostate cancer. MetS was firstly observed as a composite factor associated with prostate cancer risk in 2004, and more studies have since reported the association between MetS and prostate cancer. In biologic models proposed to explain this association, researchers note the higher concentrations of insulin and insulin-like growth factor 1 (IGF-1) in early diabetes and the lower testosterone and IGF-1 levels and higher estrogen concentrations in long-term diabetes, Whether diabetes influences levels of biomarkers such as Prostate-Specific Antigen (PSA), which is involved in the detection of prostate cancer, is still unknown. Factors influencing serum PSA levels in men include age, benign prostatic hyperplasia, prostatitis, and Body Mass Index (BMI). In this study, we examined whether PSA on the person who have insulin resistance which is often happen in men with Type 2 Diabetes Mellitus- Metabolic Syndrome. Method: This cross sectional study was performed in Surabaya private clinic. Study period was six months between January to June 2014. Plasma concentrations of glycated haemoglobin (HbA1c) and fasting and post-prandial glucose were analysed and homeostatic model assessment of insulin resistance (HOMA-IR) were calculated. HOMA-IR value more than 2.0 is considered to be positive for IR. Statistical analysis was performed using SPSS 17.0 and Spearmen’s test. Result: Fifty two male subjects were enrolled in this study. The mean age was 62.32±8.72 years old, fasting blood sugar 139.68±43.65mg/dL, mean A1C 7.89±1.80%, the mean HOMA-IR 7.14±4.77, and the mean of PSA value was 3.76±1.99 ng/dL. The PSA showed negative correlation with Insulin Resistance (r = −0.049; p < 0.005). Conclusion: The level of PSA had negative correlation with insulin resistance among men with T2DM-MetS in this study.

The Relationship between Umbilical Cord Estrogens and Perinatal Characteristics

Prenatal estrogen exposure is thought to contribute to later life diseases such as breast cancer. However, few studies have directly measured prenatal estrogens and most have relied on proposed "markers" of estrogen exposure. We used a large population-based birth cohort to directly measure the relationship between prenatal estrogens and perinatal characteristics, including putative markers of estrogen exposure. Total estrone (E1), estradiol (E2), estriol (E3), and estetrol (E4) were assayed by liquid chromatography/tandem mass spectrometry from archived mixed arterial and venous serum from 860 umbilical cord blood samples. Values for all estrogens were strongly intercorrelated. Cord estrogen concentrations did not differ between males and females. Levels of all estrogens were reduced in twins and concentrations increased with gestational age. Neither E1 nor E2 was correlated with birth weight, but E3 and E4 levels correlated weakly, whereas onset of labor was associated with higher estrogen concentrations. E1 and E2 concentrations were not associated with preeclampsia in the current pregnancy, but E3 and E4 concentrations were lower in pregnancies complicated by preeclampsia and antepartum hemorrhage. Umbilical cord estrogen concentrations vary with gestational age, mode of delivery, pregnancy complications, and twinning, but not with infant sex. Putative markers of prenatal estrogen exposure, preeclampsia, and birth weight did not correlate with direct fetal measures of the most potent estrogen (E2) but were associated with weaker estrogens (E3 and E4). Twins had lower concentrations of all estrogens. This is the largest and best characterized dataset of prenatal estrogen concentrations, measured using highly accurate mass spectrometry/spectroscopy. These observations represent the new "gold standard" for umbilical cord estrogens, and will inform the interpretation of other datasets and the early life origins of health and disease. Cancer Epidemiol Biomarkers Prev; 23(6); 946-52. ©2014 AACR.

Menstrual cycle change in thalamic glutamate decarboxylase and GABA in response to TMJ pain in rats (726.4)

Women report TMJ pain more often than men and epidemiological evidence suggests the pain response varies between men and women and over the menstrual cycle. Recent studies show TMJ responsive neurons projecting to the thalamus have different activities in male and females. Using a rat model our lab performed whole genome array screens on thalamic tissue of cycling rats. The results indicate that the transcript of both glutamate decarboxylase 1 and 2 (GAD67 and GAD65, respectively) are significantly up‐regulated in the thalamus of proestrus (high estrogen, progesterone and luteinizing hormone concentration) versus diestrus/metestrus (low estrogen, progesterone and luteinizing hormone concentration) rats. On the other hand, GABA expression (by ELISA assay) did not significantly change in the thalamic tissue during the proestrus phase. The differences in response of the enzyme and its product could be explained by the distribution of each enzyme within individual neurons. In conclusion, sex steroids could alter thalamic GABAergic signaling to effect TMJ hyperalgesia through regulation of GAD.Grant Funding Source: Supported by NIH R01 NIDCR grant: DE022129 Estrogen and TMJ Pain