WorldWideScience

Sample records for progesterone 17-alpha hydroxyprogesterone

  1. The association among cytochrome P450 3A, progesterone receptor polymorphisms, plasma 17-alpha hydroxyprogesterone caproate concentrations, and spontaneous preterm birth.

    Science.gov (United States)

    Bustos, Martha L; Caritis, Steve N; Jablonski, Kathleen A; Reddy, Uma M; Sorokin, Yoram; Manuck, Tracy; Varner, Michael W; Wapner, Ronald J; Iams, Jay D; Carpenter, Marshall W; Peaceman, Alan M; Mercer, Brian M; Sciscione, Anthony; Rouse, Dwight J; Ramin, Susan M

    2017-09-01

    Infants born preterm birth are the leading cause of mortality in children preterm birth by 33% in women with history of spontaneous preterm birth. We demonstrated previously that plasma concentrations of 17-alpha hydroxyprogesterone caproate vary widely among pregnant women and that women with 17-alpha hydroxyprogesterone caproate plasma concentrations in the lowest quartile had spontaneous preterm birth rates of 40% vs rates of 25% in those women with higher concentrations. Thus, plasma concentrations are an important factor in determining drug efficacy but the reason 17-alpha hydroxyprogesterone caproate plasma concentrations vary so much is unclear. Predominantly, 17-alpha hydroxyprogesterone caproate is metabolized by CYP3A4 and CYP3A5 enzymes. We sought to: (1) determine the relation between 17-alpha hydroxyprogesterone caproate plasma concentrations and single nucleotide polymorphisms in CYP3A4 and CYP3A5; (2) test the association between progesterone receptor single nucleotide polymorphisms and spontaneous preterm birth; and (3) test whether the association between plasma concentrations of 17-alpha hydroxyprogesterone caproate and spontaneous preterm birth varied by progesterone receptor single nucleotide polymorphisms. In this secondary analysis, we evaluated genetic polymorphism in 268 pregnant women treated with 17-alpha hydroxyprogesterone caproate, who participated in a placebo-controlled trial to evaluate the benefit of omega-3 supplementation in women with history of spontaneous preterm birth. Trough plasma concentrations of 17-alpha hydroxyprogesterone caproate were measured between 25-28 weeks of gestation after a minimum of 5 injections of 17-alpha hydroxyprogesterone caproate. We extracted DNA from maternal blood samples and genotyped the samples using TaqMan (Applied Biosystems, Foster City, CA) single nucleotide polymorphism genotyping assays for the following single nucleotide polymorphisms: CYP3A4*1B, CYP3A4*1G, CYP3A4*22, and CYP3A5*3; and rs

  2. Gestational age at initiation of 17-alpha hydroxyprogesterone caproate and recurrent preterm birth.

    Science.gov (United States)

    Ning, Angela; Vladutiu, Catherine J; Dotters-Katz, Sarah K; Goodnight, William H; Manuck, Tracy A

    2017-09-01

    Preterm birth is the leading cause of neonatal morbidity and mortality in nonanomalous neonates in the United States. Women with a previous early spontaneous preterm birth are at highest risk for recurrence. Weekly intramuscular 17-alpha hydroxyprogesterone caproate reduces the risk of recurrent prematurity. Although current guidelines recommend 17-alpha hydroxyprogesterone caproate initiation between 16 and 20 weeks, in clinical practice, 17-alpha hydroxyprogesterone caproate is started across a spectrum of gestational ages. The objective of the study was to examine the relationship between the gestational age at 17-alpha hydroxyprogesterone caproate initiation and recurrent preterm birth among women with a prior spontaneous preterm birth 16-28 weeks' gestation. This was a retrospective cohort study of women from a single tertiary care center, 2005-2016. All women with ≥1 singleton preterm births because of a spontaneous onset of contractions, preterm prelabor rupture of membranes, or painless cervical dilation between 16 and 28 weeks followed by a subsequent singleton pregnancy treated with 17-alpha hydroxyprogesterone caproate were included. Women were grouped based on quartiles of gestational age of 17-alpha hydroxyprogesterone caproate initiation (quartile 1, 14 0/7 to 16 1/7 ; quartile 2, 16 2/7 to 17 0/7 ; quartile 3, 17 1/7 to 18 6/7 ; and quartile 4, 19 0/7 to 27 5/7 ). Women with a gestational age of 17-alpha hydroxyprogesterone caproate initiation in quartiles 1 and 2 were considered to have early-start 17-alpha hydroxyprogesterone caproate; those in quartiles 3 and 4 were considered to have late-start 17-alpha hydroxyprogesterone caproate. The primary outcome was recurrent preterm birth preterm birth preterm birth preterm birth preterm birth preterm birth preterm birth among women with a prior spontaneous preterm birth 16-28 weeks are high. Women beginning 17-alpha

  3. Ovulation rate and litter size in gilts immunized against androstenedione and 17alpha-hydroxyprogesterone.

    Science.gov (United States)

    Kreider, D L; Rorie, R; Brown, D; Maxwell, C; Miller, F; Wright, S; Brown, A

    2001-07-01

    Two experiments were conducted to evaluate the effects of the immunization of gilts against ovarian steroids on ovulation rate and litter size. In Exp. 1, gilts (n = five gilts/treatment) at 165+/-1.6 d of age were immunized against either carrier (Control), androstenedione, or 17alpha-hydroxyprogesterone. Age at puberty and estrous cycle length averaged 208+/-5.5 (P = 0.67) and 20.3+/-2.8 d (P = 0.41), respectively, and were not affected by treatment. The androstenedione- and 17alpha-hydroxyprogesterone immunized gilts had higher (P gilts than in the Controls (12.6 vs 10.5+/-0.6, P gilts can be increased by immunization against 17alpha-hydroxyprogesterone.

  4. Comparison of Risk of Preterm Labor between Vaginal Progesterone and17-Alpha-Hydroxy-Progesterone Caproate in Women with Threatened Abortion: A Randomized Clinical Trial

    Directory of Open Access Journals (Sweden)

    Beigi Abootaleb

    2016-07-01

    Full Text Available Objective Threatened miscarriage is a common complication in pregnancy that leads to adverse pregnancy outcomes such as preterm labor. This study aimed to compare the vaginal progesterone (Cyclogest versus 17-alpha-hydroxyprogesterone caproate (Proluton on preventing preterm labor in pregnant women with threatened abortion at less than 34 weeks’ gestational age. Materials and methods This balanced randomized, double-blind, single-center controlled clinical trial included 190 women with threatened abortion. They were then randomly allocated into Cyclogest (n=95 and 17-alpha-hydroxyprogesterone caproate (Proluton, n=95 groups. Interested outcome was preterm labor less than 34 weeks. The Pearson chi-square and Student’s t test were used to compare two groups. The data were analyzed by Stata software version 13. Results The risks of preterm labor less than 34 weeks in Proluton and Cyclogest groups were 8.6 and 6.52%, respectively. There was no significant difference for risk of preterm labor less than 34 weeks [relative ratio (RR: 1.31, 95% confidence interval (CI: 0.47- 3.66, P=0.59] between two groups. Conclusion Risk of preterm labor in the vaginal progesterone group and 17-alpha-hydroxyprogesterone caproate group in pregnant women with threatened abortion is the same (Registration Number: IRCT2014123120504N1.

  5. Racial and ethnic disparities in use of 17-alpha hydroxyprogesterone caproate for prevention of preterm birth.

    Science.gov (United States)

    Yee, Lynn M; Liu, Lilly Y; Sakowicz, Allie; Bolden, Janelle R; Miller, Emily S

    2016-03-01

    Racial/ethnic disparities in preterm birth remain a major public health challenge in the United States. While 17-alpha hydroxyprogesterone caproate (17OHP-C) is recommended for preterm birth prevention in women with a prior preterm birth, non-Hispanic black women continue to experience higher rates of recurrent preterm birth than white women receiving the same treatment. Further investigation of disparities in 17OHP-C use and adherence is warranted. We sought to evaluate whether racial and ethnic disparities exist in the use of and adherence to 17OHP-C within a population of eligible women. This was a retrospective cohort study of women with a prior spontaneous, singleton preterm birth who were eligible for 17OHP-C for preterm birth prevention and received care at a single institution from 2010 through 2014. Associations between self-identified race/ethnicity (non-Hispanic black vs women in all other racial/ethnic groups) and documented counseling about 17OHP-C, receipt of any 17OHP-C, and adherence to 17OHP-C administration were each estimated by bivariable analysis and multivariable logistic regression. Adherence to 17OHP-C was defined as not >1 missed dose, initiation racial/ethnic groups. After adjustment for potential confounders, non-Hispanic black women were significantly less likely to be adherent to 17OHP-C (adjusted odds ratio, 0.16; 95% confidence interval, 0.04-0.65). A significant interaction between non-Hispanic black race/ethnicity and public insurance was identified (adjusted odds ratio, 0.16; 95% confidence interval, 0.05-0.52). In a diverse cohort of women eligible for preterm birth prevention, non-Hispanic black women are at an increased risk of nonadherence to 17OHP-C. Non-Hispanic black women with public insurance are at a particularly increased risk of nonadherence. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Functional effects of 17alpha-hydroxyprogesterone caproate (17P on human myometrial contractility in vitro

    Directory of Open Access Journals (Sweden)

    Morrison John J

    2004-12-01

    Full Text Available Abstract Background 17alpha-hydroxyprogesterone caproate (17P administration reportedly improves outcome for women with a previous spontaneous preterm delivery. This study, using in vitro strips of human uterine smooth muscle, aimed to investigate the direct non-genomic effects of 17P on spontaneous and induced contractions in tissues obtained during pregnancy, and in the non-pregnant state. Methods Biopsies of human myometrium were obtained at elective cesarean section, and from hysterectomy specimens, and dissected strips suspended for isometric recordings. The effects of 17P (1 nmol/L -10 micro mol/L on spontaneous and agonist-induced (oxytocin 0.5 nmol/L for pregnant, phenylephrine 10 μmol/L for non-pregnant contractions were measured. Integrals of contractile activity, including the mean maximal inhibition values (MMI observed at the maximal concentration, were compared with those from simultaneously run control strips. Results There was no significant direct effect exerted by 17P on pregnant or non-pregnant human myometrial contractility. The MMI ± SEM for spontaneous contractions in pregnant myometrium was 4.9% ± 7.2 (n = 6; P = 0.309 and for oxytocin-induced contractions was 2.2% ± 1.3 (n = 6; P = 0.128. For non-pregnant myometrium, the MMI ± SEM for spontaneous contractions was 8.8% ± 11.0 (n = 6; P = 0.121 and for phenylephrine induced contractions was -7.9% ± 6.5 (n = 6; P = 0.966. Conclusions The putative benefits of 17P for preterm labor prevention are not achieved, even partially, by a direct utero-relaxant effect. These findings outline the possibility that genomic effects of 17P, achieved over long periods of administration, are required for its reported therapeutic benefits.

  7. The 11alpha and 17alpha-progesterone hydroxylases of Rhizopus nigricans NRRL 1477.

    Science.gov (United States)

    Allam, A M; el-Kady, I A

    1975-01-01

    Differential induction of cultures of Rhizopus nigricans indicated that hydroxylation of progesterone at the 11alpha- and 17alpha-positions is due to two separate enzymes. This is supported by the finding that 11alpha- and 17alpha-hydroxylating activities are separated by differential centrigufation of cell-free extracts. The feasibility of introducing a hydroxyl group at the 11alpha- or 17alpha-position of hydroxylated progesterone derivatives was tested.

  8. [Lanthanide fluorescence immunoassay of 17alpha-hydroxyprogesterone in dried blood samples for neonatal screening for adrenogenital syndrome].

    Science.gov (United States)

    Bekman, N I; Laricheva, S Iu; Pomelova, V G; Osin, N S

    2010-12-01

    The first Russian assay of 17alpha-hydroxyprogesterone in dried blood spots has been developed to use for neonatal screening for adrenogenital syndrome (AGS). The technique is modeled on solid-phase lanthanide fluorescence immunoassay with time-resolution detection and it ensures the hormone to be determined in a 3.2-mm dried blood spot in the concentration range of 0 to 400 nmol/l, the coefficient of variation being not greater than 15%, and the results correlated with those of the DELFIA Neo170HP test system. The tests of 387 dried blood samples carried out in three regions have demonstrated the efficiency of the technique for screening and verifying neonatal AGS.

  9. A national survey examining obstetrician perspectives on use of 17-alpha hydroxyprogesterone caproate post-US FDA approval.

    Science.gov (United States)

    Rebarber, Andrei; Fox, Nathan; Klauser, Chad K; Saltzman, Daniel; Roman, Ashley S

    2013-08-01

    A randomized study published in 2003 by the National Institute of Child Health and Human Development Maternal Fetal Medicine Units network showed efficacy of 17-alpha hydroxyprogesterone caproate (17P) for the prevention of recurrent preterm delivery. Between 2003 and 2011 the drug was often provided by compounding pharmacies. In 2011, the US Food and Drug Administration (FDA) approved the drug for this indication. The objective of this study was to evaluate the impact of FDA approval on physician attitudes and perceptions regarding use of 17P as a drug for preventing recurrent preterm delivery. A 10-min online survey using a structure closed-ended questionnaire format was designed and administered from 17 June 2011 to 7 July 2011 among 401 obstetricians distributed evenly throughout the USA. There is nearly universal awareness of 17P for the prevention of preterm birth (93 %), with a large majority (80 %) of obstetricians having reported prescribing the medication. However, surveyed physicians reported that the average proportion of eligible patients seen in their practice but not prescribed 17P in 2009-2010 was 41 %. Financial and logistical barriers carried the most weight (approximately 75 %) in the decision not to prescribe 17P to an eligible patient. Forty-one percent of respondents cited lack of FDA approval of 17P as a deterrent to prescribing the medication. Thirty-nine percent of respondents had professional liability concerns regarding prescribing compounded 17P. Assuming the same out-of-pocket expense for patients, two-thirds of obstetricians would choose to prescribe Makena(®). Awareness of 17P for the prevention of preterm birth among obstetricians is high. FDA-approved medications seem to have physician preference due to enhanced assurance for product efficacy and safety.

  10. Relation of body mass index to frequency of recurrent preterm birth in women treated with 17-alpha hydroxyprogesterone caproate.

    Science.gov (United States)

    Co, Aila L; Walker, Hetty C; Hade, Erinn M; Iams, Jay D

    2015-08-01

    The standard weekly dose of 17-alpha hydroxyprogesterone caproate (17OHP-C; 250 mg/wk) to reduce the risk of recurrent preterm birth was adopted without regard to patient characteristics. We examined the relationship between prepregnancy body mass index (BMI) and gestational age at birth after 17OHP-C prophylaxis. We hypothesized that rates of births before 32, 35, and 37 weeks of gestation would be increased in women with a BMI of 25 kg/m(2) or greater. A retrospective cohort study was conducted from a deidentified database of women treated with 17OHP-C for prior spontaneous preterm birth. The frequency of recurrent preterm delivery before 32, 35, and 37 weeks of gestation was investigated for women with a BMI less than 25 kg/m(2) compared with women with a BMI of 25 kg/m(2) or greater. The adjusted relative risk of preterm delivery was estimated through a modified Poisson regression approach. Of 390 women who met inclusion criteria, 60 (15.4%) delivered before 32 weeks, 89 (22.8%) before 35 weeks, and 156 (40.0%) before 37 weeks. A total of 174 women had a BMI less than 25 kg/m(2) (mean [SD], 21.2 [2.5]) and 216 had a BMI of 25 kg/m(2) or greater (mean [SD], 33.5 [6.7]). Risk of birth before 32 weeks was 1.7 times higher on average (adjusted relative risk, 1.7; 95% confidence interval, 1.05-2.77) in overweight women than in women with a BMI less than 25 kg/m(2), adjusting for age, race, smoking, and short cervix. There was no difference in the risk of preterm birth before 35 or 37 weeks. Among pregnant women receiving 17OHP-C prophylaxis for a prior preterm birth, recurrent preterm birth before 32 weeks was significantly more common in those women whose prepregnancy BMI was 25 kg/m(2) or greater than in women with BMI less than 25 kg/m(2). This observation is consistent with pharmacological studies suggesting that dosing regimens of 17OHP-C may affect efficacy. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. Diagnosis of congenital adrenal hyperplasia by rapid determination of 17alpha-hydroxyprogesterone in dried blood spots by gas chromatography/mass spectrometry following microwave-assisted silylation.

    Science.gov (United States)

    Deng, Chunhui; Ji, Jie; Zhang, Lijuan; Zhang, Xiangmin

    2005-01-01

    17alpha-Hydroxyprogesterone (17OHP) is considered to be the biomarker of congential adrenal hyperplasia (CAH). Screening for CAH in newborns by measuring levels of the biomarker of 17OHP has become routine. In the work, a rapid, simple and sensitive technique was developed for the diagnosis of neonatal CAH by the quantitative analysis of 17OHP in neonatal blood spots. The technique was based on microwave-assisted silylation (MAS) followed by gas chromatography/mass spectrometry (GC/MS). In the method, fast derivatization of 17OHP with N,O-bis(trimethylsilyl)trifluoroacetamide was performed by using microwave irradiation, and the trimethylsilyl derivative thus formed was analyzed by GC/MS. The results of the experiment indicate that MAS followed by GC/MS analysis is a rapid, simple and sensitive method for the determination of 17OHP in blood samples. The proposed technique has been shown to have potential as a powerful tool for the rapid diagnosis of neonatal CAH. (c) 2005 John Wiley & Sons, Ltd.

  12. 17alpha-hydroxy-progesterone effects on cervical proinflammatory agents in women at risk for preterm delivery.

    Science.gov (United States)

    Facchinetti, Fabio; Dante, Giulia; Venturini, Paolo; Paganelli, Simone; Volpe, Annibale

    2008-09-01

    We evaluated if the inhibitory effect of 17alpha-hydroxyprogesterone caproate (17P) on cervical ripening is mediated by cervical proinflammatory agents. Women with singleton pregnancy and intact membranes, between 25 and 33 weeks + 6 days, were randomly allocated either to observation (22 cases, controls) or to receive 341 mg of intramuscular 17P (23 cases, 17P group), twice a week, until 36 weeks. Just before randomization, 7 and 21 days later, a cervical swab for interleukin (IL)-1beta, IL-6, IL-8, tumor necrosis factor alpha (TNF-alpha), and nitrates/nitrites (NOx) assays was collected. Moreover, an ultrasound measure of cervical length (CL) was performed at the same time. At randomization, both groups of women showed similar levels of cervical ILs and NOx. In the 17P group, cervical IL-1beta levels were significantly decreased at day 21 ( P = 0.036); in controls, they remained stable throughout the observation period. There was no significant change in IL-6, IL-8, TNF-alpha, and NOx in either group. Women in the control group had a progressive CL shortening until day 21 (median shortening of 4 mm), and this shortening was significantly less in the 17P group (median shortening of 2 mm; P = 0.017). In patients at risk of preterm labor, high-dose 17P simultaneously inhibits both cervical proinflammatory IL-1beta secretion and the progressive shortening of the cervix.

  13. Synthesis of the 7alpha-cyano-(17alpha,20E/Z)-[125I]iodovinyl-19-nortestosterones: potential radioligands for androgen and progesterone receptors.

    Science.gov (United States)

    Ali, Hasrat; Rousseau, Jacques; Ahmed, Naseem; Guertin, Veronique; Hochberg, Richard B; van Lier, Johan E

    2003-12-01

    We report the preparation of the 7alpha-cyano derivative of the isomeric (17alpha,20E/Z)-[125I]iodovinyl-19-nortestosterones (IVNT) together with their binding affinity for the androgen receptor (AR) and their biodistribution in two different animal models. The cyano group was introduced at the 7alpha-position by hydrocyanation of 4,6-estradien-17beta-ol-3-one with diethylaluminum cyanide. Selective protection of the A-ring enone system as the dienol ether followed by ethynylation and deprotection under base and acid hydrolysis condition gave 7alpha-cyano-17alpha-ethynyl-19-nortestosterone. The stannyl derivatives were prepared by addition of tri-n-butylstannyl hydride and converted stereospecifically to the corresponding [125I]iodovinyl analog using [125I]NaI and H2O2. The [125I]iodovinylsteroids were intravenously administered to male rats and estrogen-primed immature female rats and tissue uptake was measured up to 6h post-injection. Co-administration of NLP-004 or ORG-2058, highly selective ligands for the progesterone receptor, to the female rats did not affect uterus uptake of the 125I-ligands. However co-injection of testosterone to DES-primed male rats induced a marked increase in prostate uptake of the 20Z-isomer of 7alpha-cyano-[125I]-IVNT. The relative binding affinity (RBA) of either 7alpha-cyano-(17alpha,20E/Z)-IVNT isomer for the AR is low (RBA=4 and 3, respectively, versus 100 for 5alpha-dihydrotestosterone (DHT)), suggesting the absence of a possible role of the AR in the localization process. These findings contrast previously reported data for the analogous 7alpha-methyl-[125I]-IVNT where co-administration of testosterone was shown to result in a 50% drop in prostate uptake. These data indicate that the addition of an electron withdrawing 7alpha-cyano group to 123I-labeled nortestosterone derivatives does not improve their potential to serve as SPECT agents for the imaging of AR densities in the prostate.

  14. In an in-vitro model using human fetal membranes, 17-α hydroxyprogesterone caproate is not an optimal progestogen for inhibition of fetal membrane weakening.

    Science.gov (United States)

    Kumar, Deepak; Moore, Robert M; Mercer, Brian M; Mansour, Joseph M; Mesiano, Sam; Schatz, Frederick; Lockwood, Charles J; Moore, John J

    2017-12-01

    The progestogen 17-α hydroxyprogesterone caproate (17-OHPC) is 1 of only 2 agents recommended for clinical use in the prevention of spontaneous preterm delivery, and studies of its efficacy have been conflicting. We have developed an in-vitro model to study the fetal membrane weakening process that leads to rupture in preterm premature rupture of the fetal membranes (pPROM). Inflammation/infection associated with tumor necrosis factor-α (TNF-α) induction and decidual bleeding/abruption associated thrombin release are leading causes of preterm premature rupture of the fetal membranes. Both agents (TNF-α and thrombin) cause fetal membrane weakening in the model system. Furthermore, granulocyte-macrophage colony-stimulating factor (GM-CSF) is a critical intermediate for both TNF-α and thrombin-induced fetal membrane weakening. In a previous report, we demonstrated that 3 progestogens, progesterone, 17-alpha hydroxyprogesterone (17-OHP), and medroxyprogesterone acetate (MPA), each inhibit both TNF-α- and thrombin-induced fetal membrane weakening at 2 distinct points of the fetal membrane weakening pathway. Each block both the production of and the downstream action of the critical intermediate granulocyte-macrophage colony-stimulating factor. The objective of the study was to characterize the inhibitory effects of 17-OHPC on TNF-α- and thrombin-induced fetal membrane weakening in vitro. Full-thickness human fetal membrane fragments from uncomplicated term repeat cesarean deliveries were mounted in 2.5 cm Transwell inserts and cultured with/without 17-alpha hydroxyprogesterone caproate (10-9 to 10-7 M). After 24 hours, medium (supernatant) was removed and replaced with/without the addition of tumor necrosis factor-alpha (20 ng/mL) or thrombin (10 U/mL) or granulocyte-macrophage colony-stimulating factor (200 ng/mL). After 48 hours of culture, medium from the maternal side compartment of the model was assayed for granulocyte-macrophage colony-stimulating factor

  15. Progesterone

    Science.gov (United States)

    ... cancer. Progesterone is also used to bring on menstruation (period) in women of childbearing age who have ... in the uterus. It works to bring on menstruation by replacing the natural progesterone that some women ...

  16. Vaginal progesterone vs intramuscular 17α-hydroxyprogesterone caproate for prevention of recurrent spontaneous preterm birth in singleton gestations: systematic review and meta-analysis of randomized controlled trials.

    Science.gov (United States)

    Saccone, G; Khalifeh, A; Elimian, A; Bahrami, E; Chaman-Ara, K; Bahrami, M A; Berghella, V

    2017-03-01

    Randomized controlled trials (RCTs) have recently compared intramuscular 17α-hydroxyprogesterone caproate (17-OHPC) with vaginal progesterone for reducing the risk of spontaneous preterm birth (SPTB) in singleton gestations with prior SPTB. The aim of this systematic review and meta-analysis was to evaluate the efficacy of vaginal progesterone compared with 17-OHPC in prevention of SPTB in singleton gestations with prior SPTB. Searches of electronic databases were performed to identify all RCTs of asymptomatic singleton gestations with prior SPTB that were randomized to prophylactic treatment with either vaginal progesterone (intervention group) or intramuscular 17-OHPC (comparison group). No restrictions for language or geographic location were applied. The primary outcome was SPTB PROGESTERONA VAGINAL Y EL 17Α-HIDROXIPROGESTERONA CAPROATO INTRAMUSCULAR PARA LA PREVENCIÓN DEL PARTO PRETÉRMINO ESPONTÁNEO RECURRENTE EN EMBARAZOS CON FETO ÚNICO: REVISIÓN SISTEMÁTICA Y METAANÁLISIS DE ENSAYOS CONTROLADOS ALEATORIOS: RESUMEN OBJETIVO: Recientemente se han realizado varios ensayos controlados aleatorios (ECA) que comparaban el caproato de 17α-hidroxiprogesterona (17-OHPC, por sus siglas en inglés) por vía intramuscular con la progesterona por vía vaginal para la reducción del riesgo de parto pretérmino espontáneo (PPTE) en embarazos con feto único de gestantes con historial de PPTE. El objetivo de esta revisión sistemática y metaanálisis fue evaluar la eficacia de la progesterona vaginal en comparación con la 17-OHPC en la prevención de embarazos con feto único de gestantes con historial de PPTE. MÉTODOS: Se realizaron búsquedas en bases de datos electrónicas para identificar todos los ECA con embarazos de feto único asintomáticos con historial de PPTE antes de ser asignados al azar a un tratamiento profiláctico, ya fuera con progesterona vaginal (grupo de intervención) o con 17-OHPC intramuscular (grupo de control). No se aplicaron

  17. Study of RNA interference inhibiting rat ovarian androgen biosynthesis by depressing 17alpha-hydroxylase/17, 20-lyase activity in vivo

    Directory of Open Access Journals (Sweden)

    Yang Xing

    2009-07-01

    Full Text Available Abstract Background 17alpha-hydroxylase/17, 20-lyase encoded by CYP17 is the key enzyme in androgen biosynthesis pathway. Previous studies demonstrated the accentuation of the enzyme in patients with polycystic ovary syndrome (PCOS was the most important mechanism of androgen excess. We chose CYP17 as the therapeutic target, trying to suppress the activity of 17alpha-hydroxylase/17, 20-lyase and inhibit androgen biosynthesis by silencing the expression of CYP17 in the rat ovary. Methods Three CYP17-targeting and one negative control oligonucleotides were designed and used in the present study. The silence efficiency of lentivirus shRNA was assessed by qRT-PCR, Western blotting and hormone assay. After subcapsular injection of lentivirus shRNA in rat ovary, the delivery efficiency was evaluated by GFP fluorescence and qPCR. Total RNA was extracted from rat ovary for CYP17 mRNA determination and rat serum was collected for hormone measurement. Results In total, three CYP17-targeting lentivirus shRNAs were synthesized. The results showed that all of them had a silencing effect on CYP17 mRNA and protein. Moreover, androstenedione secreted by rat theca interstitial cells (TIC in the RNAi group declined significantly compared with that in the control group. Two weeks after rat ovarian subcapsular injection of chosen CYP17 shRNA, the GFP fluorescence of frozen ovarian sections could be seen clearly under fluorescence microscope. It also showed that the GFP DNA level increased significantly, and its relative expression level was 7.42 times higher than that in the control group. Simultaneously, shRNA treatment significantly decreased CYP17 mRNA and protein levels at 61% and 54%, respectively. Hormone assay showed that all the levels of androstenedione, 17-hydroxyprogesterone and testosterone declined to a certain degree, but progesterone levels declined significantly. Conclusion The present study proves for the first time that ovarian androgen

  18. Microbial transformation of synthetic estrogen 17 alpha-ethinylestradiol

    Czech Academy of Sciences Publication Activity Database

    Cajthaml, Tomáš; Křesinová, Zdena; Svobodová, Kateřina; Sigler, Karel; Řezanka, Tomáš

    2009-01-01

    Roč. 157, č. 12 (2009), s. 3325-3335 ISSN 0269-7491 R&D Projects: GA MŠk LC06066; GA AV ČR KJB600200613 Institutional research plan: CEZ:AV0Z50200510 Keywords : 17 alpha-Ethinylestradiol * Microbial biodegradation * Ligninolytic fungi Subject RIV: EE - Microbiology, Virology Impact factor: 3.426, year: 2009

  19. Microbial transformation of synthetic estrogen 17alpha-ethinylestradiol

    Energy Technology Data Exchange (ETDEWEB)

    Cajthaml, Tomas, E-mail: cajthaml@biomed.cas.c [Institute of Microbiology, Academy of Sciences of the Czech Republic, Videnska 1083, CZ-142 20 Prague 4 (Czech Republic); Kresinova, Zdena; Svobodova, Katerina; Sigler, Karel; Rezanka, Tomas [Institute of Microbiology, Academy of Sciences of the Czech Republic, Videnska 1083, CZ-142 20 Prague 4 (Czech Republic)

    2009-12-15

    Natural estrogens such as estrone, 17beta-estradiol, estriol, and the particularly recalcitrant synthetic estrogen 17alpha-ethinylestradiol used as oral contraceptive, accumulate in the environment and may give rise to health problems. The processes participating in their removal from soil, wastewater, water-sediments, groundwater-aquifer material, and wastewater or sewage treatment plant effluents may involve the action of bacterial and microbial consortia, and in some cases fungi and algae. This review discusses the different efficiencies of bacterial degradation of 17alpha-ethinylestradiol under aerobic and anaerobic conditions, the role of sulfate-, nitrate-, and iron-reducing conditions in anaerobic degradation, and the role of sorption. The participation of autotrophic ammonia oxidizing bacteria and heterotrophic bacteria in cometabolic degradation of estrogens, the estrogen-degrading action of ligninolytic fungi and their extracellular enzymes (lignin peroxidase, manganese-dependent peroxidase, versatile peroxidase, laccase), and of algae are discussed in detail. - Current knowledge of 17alpha-ethinylestradiol microbial transformation is summarized.

  20. 21 CFR 862.1395 - 17-Hydroxyprogesterone test system.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false 17-Hydroxyprogesterone test system. 862.1395 Section 862.1395 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES.... Measurements of 17-hydroxyprogesterone are used in the diagnosis and treatment of various disorders of the...

  1. Vasoactive intestinal peptide-induced expression of cytochrome P450 cholesterol side-chain cleavage and 17 alpha-hydroxylase enzyme activity in hen granulosa cells.

    Science.gov (United States)

    Johnson, A L; Li, Z; Gibney, J A; Malamed, S

    1994-08-01

    Experiments were conducted to determine whether vasoactive intestinal peptide (VIP) can regulate expression of cytochrome P450 side-chain cleavage (P450scc) and P450 17 alpha-hydroxylase (P450 17 alpha-OH) mRNA levels and enzyme activity in granulosa cells from nonhierarchal (6-8-mm) follicles. Initial studies demonstrated that immunoreactive VIP is localized within the theca (but not granulosa) layer of both resting (< 0.5-mm follicles) and 6-8-mm follicles, thus providing a potential paracrine mechanism of action for VIP. While short-term (3 h) incubation of granulosa cells with VIP (0.001-1.0 microM) failed to stimulate progesterone production from 6-8-mm follicle granulosa cells, a 4-h culture period in the presence of VIP resulted in increased cyclic AMP (cAMP) accumulation, and a 24-h culture period resulted in progesterone synthesis and increased P450scc mRNA levels; control levels of each endpoint measurement were not altered within the period observed. By contrast, culture with the growth factor transforming growth factor alpha (TGF alpha) in the presence of VIP (1 microM) prevented increases in P450scc mRNA levels and progesterone production. Similar effects of VIP and TGF alpha in the presence of VIP were demonstrated for P450 17 alpha-OH mRNA levels and enzyme activity. Finally, there was an additive effect of VIP (0.1 microM) plus recombinant human (rh) FSH (100 mIU) on the initiation of progesterone production in cultured 6-8-mm follicle granulosa cells compared to the addition of VIP or rhFSH alone.(ABSTRACT TRUNCATED AT 250 WORDS)

  2. Evidence that exposure to progesterone alone is a sufficient stimulus to cause a precipitous rise in the immunomodulatory protein the progesterone induced blocking factor (PIBF).

    Science.gov (United States)

    Cohen, Rachael A; Check, Jerome H; Dougherty, Michael P

    2016-02-01

    To determine if exposure to progesterone alone is sufficient to increase the production of the immunomodulatory protein known as the progesterone induced blocking factor (PIBF). Also to determine what method of progesterone delivery or form of P best stimulates PIBF secretion. Serum samples from patients with infertility and paid volunteers were evaluated for both PIBF and progesterone at various times during the follicular phase and the luteal phase in both natural cycles and cycles involving embryo transfer after endogenous and exogenous progesterone exposure and after various synthetic progestins. PIBF was measured by a non-commercial research ELISA assay. Comparisons were made of serum PIBF before and after exposure to progesterone, 17-hydroxyprogesterone, and oral contraceptives. PIBF was also measured before and after transfer of embryos. Progesterone alone without exposure to the fetal allogeneic stimulus was able to produce a marked increase in serum PIBF. Neither a synthetic progestin (19-nortestosterone derivative) nor 17-hydroxyprogesterone caused an increase in PIBF. Some PIBF is generally detected even in the follicular phase. A previous concept considered that an allogeneic stimulus, e.g., from the fetal semi-allograft, was necessary to induce de novo progesterone receptors in gamma delta T cells, which, in turn, when exposed to a high concentration of progesterone, would secrete high levels of PIBF. These data show that exposure to an allogeneic stimulus is not needed to cause a marked rise in PIBF, merely progesterone alone is sufficient.

  3. Progesterone for the prevention of preterm birth in women with multiple pregnancies: the AMPHIA trial

    Directory of Open Access Journals (Sweden)

    Scheepers Hubertina CJ

    2007-06-01

    Full Text Available Abstract Background 15% of multiple pregnancies ends in a preterm delivery, which can lead to mortality and severe long term neonatal morbidity. At present, no generally accepted strategy for the prevention of preterm birth in multiple pregnancies exists. Prophylactic administration of 17-alpha hydroxyprogesterone caproate (17OHPC has proven to be effective in the prevention of preterm birth in women with singleton pregnancies with a previous preterm delivery. At present, there are no data on the effectiveness of progesterone in the prevention of preterm birth in multiple pregnancies. Methods/Design We aim to investigate the hypothesis that 17OHPC will reduce the incidence of the composite neonatal morbidity of neonates by reducing the early preterm birth rate in multiple pregnancies. Women with a multiple pregnancy at a gestational age between 15 and 20 weeks of gestation will be entered in a placebo-controlled, double blinded randomised study comparing weekly 250 mg 17OHPC intramuscular injections from 16–20 weeks up to 36 weeks of gestation versus placebo. At study entry, cervical length will be measured. The primary outcome is composite bad neonatal condition (perinatal death or severe morbidity. Secondary outcome measures are time to delivery, preterm birth rate before 32 and 37 weeks, days of admission in neonatal intensive care unit, maternal morbidity, maternal admission days for preterm labour and costs. We need to include 660 women to indicate a reduction in bad neonatal outcome from 15% to 8%. Analysis will be by intention to treat. We will also analyse whether the treatment effect is dependent on cervical length. Discussion This trial will provide evidence as to whether or not 17OHPC-treatment is an effective means of preventing bad neonatal outcome due to preterm birth in multiple pregnancies. Trial registration Current Controlled Trials ISRCTN40512715

  4. Amniotic fluid 17-hydroxyprogesterone in early pregnancy.

    Science.gov (United States)

    Sulcová, J; Macek, M; Chudoba, D; Hubl, W; Hill, M; Stárka, L

    1994-12-01

    The results of measurement of 17-hydroxyprogesterone (17-OH-P) in 125 samples of amniotic fluid (AF) from early amniocenteses are presented. The fetuses from all pregnancies studied were unaffected by congenital adrenal hyperphasia caused by 21-hydroxylase deficiency. The AF 17-OH-P level increases slightly but significantly between the 11th and 15th week of gestation, with a maximum in the 14th week. There is no difference between the values measured in male and female fetuses. The AF 17-OH-P levels from the early gestation were compared with those from the 16th-22nd week of pregnancy (published previously). The overall differences of AF 17-OH-P concentrations when considered in all gestational age groups in the whole period 12-22 weeks were statistically insignificant. Thus, the biochemical prenatal diagnosis of congenital adrenal hyperplasia due to 21-hydroxylase deficiency and control of its early fetal treatment could be carried out starting from the end of the first trimester in the same way as at the later period of gestation.

  5. In vitro biosynthesis of steroids from progesterone by the ovaries and pyloric ceca of the starfish Asterias rubens

    NARCIS (Netherlands)

    Schoenmakers, H.J.N.; Voogt, P.A.

    In vitro biosynthesis of steroids from progesterone in ovaries and pyloric ceca of Asterias rubens has been investigated. The biosynthesis of 17α-hydroxyprogesterone, androstenedione, testosterone, 20α-dihydroprogesterone, 11-desoxycorticosterone, and 5α-pregnane-3,20-dione could be demonstrated to

  6. ''Blood-spot 17-hydroxy-progesterone'' level in neonates and infants suffering from congenital adrenal hyperplasia (CAH)

    Energy Technology Data Exchange (ETDEWEB)

    Solyom, J.; Babosa, M.; Dizseri, T.; Galambosi, L.; Hervei, S.; Marossy, P.; Solyom, E.; Vagvoelgyi, E. (Semmelweis Orvostudomanyi Egyetem, Budapest (Hungary); Pecsi Orvostudomanyi Egyetem (Hungary); Foevarosi Heim Pal Korhaz, Budapest (Hungary)

    1982-01-01

    A new radioimmunoassay (RIA) procedure was developed to measure the blood serum concentration of 17-hydroxy-progesterone. Blood samples of neonates were dried on filter paper and the measurement was carried out from 3 ..mu..l serum extracted from the filter. The method is suitable for early diagnosis of CAH and for routine neonate-screening.

  7. 17 alpha-substituted analogs of estradiol for the development of fluorescent estrogen receptor ligands.

    Science.gov (United States)

    Salman, M; Reddy, B R; Delgado, P; Stotter, P L; Fulcher, L C; Chamness, G C

    1991-07-01

    For the successful development of a high-affinity fluorophore-estradiol conjugate, the fluorophore must be attached to the estradiol molecule at a position that interferes least with its binding to the receptor. We have concentrated on 17 alpha substituents as models for fluorophore attachment, based on literature precedent and on our earlier work with small 17 alpha side chains. In this report, we describe syntheses and estrogen receptor binding affinities of 19 analogs of estradiol substituted in the 17 alpha position with larger side chains (of six to 11 carbons), some of which may be synthetically modified to link a fluorophore. These analogs were synthesized either by nucleophilic cleavage of estrone-17 beta-oxirane 3-benzyl ether and subsequent debenzylation (4 to 18), by cross-coupling of alkynes (21 to 24), by alkylation of 17 alpha-ethynylestradiol 3,17-bis(tetrahydropyranyl ether) and subsequent acidic hydrolysis (25 to 28), or by reacting estrone either with appropriate aryl/alkynyllithium reagents (29, 30, and 32) or with benzylmagnesium bromide (31). Relative binding affinities of these newly synthesized analogs were determined for estrogen receptor (rat uterus) using a standard competition assay. The results suggest that analogs with reduced mobility and/or more polarizable electron density in the side chain generally bind more strongly to the receptor. The relative affinities of several selected compounds were also determined in the presence of 4% dimethylformamide; some compounds bearing larger, nonpolar 17 alpha substituents showed dramatically improved affinities, while affinities for compounds with shorter nonpolar side chains remained largely unchanged. These binding affinity results should be useful in designing new high-affinity fluorescent ligands for the estrogen receptor.

  8. Progesterone to prevent spontaneous preterm birth

    Science.gov (United States)

    Romero, Roberto; Yeo, Lami; Chaemsaithong, Piya; Chaiworapongsa, Tinnakorn; Hassan, Sonia

    2014-01-01

    Summary Preterm birth is the leading cause of perinatal morbidity and mortality worldwide, and its prevention is an important healthcare priority. Preterm parturition is one of the ‘great obstetrical syndromes’ and is caused by multiple etiologies. One of the mechanisms of disease is the untimely decline in progesterone action, which can be manifested by a sonographic short cervix in the midtrimester. The detection of a short cervix in the midtrimester is a powerful risk factor for preterm delivery. Vaginal progesterone can reduce the rate of preterm delivery by 45%, and the rate of neonatal morbidity (admission to neonatal intensive care unit, respiratory distress syndrome, need for mechanical ventilation, etc.). To prevent one case of spontaneous preterm birth preterm birth in women with a short cervix both with and without a prior history of preterm birth. In patients with a prior history of preterm birth, vaginal progesterone is as effective as cervical cerclage to prevent preterm delivery. 17α-Hydroxyprogesterone caproate has not been shown to be effective in reducing the rate of spontaneous preterm birth in women with a short cervix. PMID:24315687

  9. Impairment of male reproduction in adult rats exposed to hydroxyprogesterone caproate in utero

    Science.gov (United States)

    Pushpalatha, T.; Ramachandra Reddy, P.; Sreenivasula Reddy, P.

    Hydroxyprogesterone caproate is one of the most effective and widely used drugs for the treatment of uterine bleeding and threatened miscarriage in women. Hydroxyprogesterone caproate was administered to pregnant rats in order to assess the effect of intraperitoneal exposure to supranormal levels of hydroxyprogesterone caproate on the male reproductive potential in the first generation. The cauda epididymal sperm count and motility decreased significantly in rats exposed to hydroxyprogesterone caproate during embryonic development, when compared with control rats. The levels of serum testosterone decreased with an increase in follicle stimulating hormone and luteinizing hormone in adult rats exposed to hydroxyprogesterone caproate during the embryonic stage. It was suggested that the impairment of male reproductive performance could be mediated through the inhibition of testosterone production.

  10. The rebirth of progesterone in the prevention of preterm labor.

    Science.gov (United States)

    Schmouder, Vanessa M; Prescott, Gina M; Franco, Albert; Fan-Havard, Patty

    2013-04-01

    To evaluate data since 2003 on the efficacy and safety of progesterone supplementation in the prevention of preterm labor. A MEDLINE and Ovid database search (January 2003-September 2012) was performed using the search terms preterm, progesterone, and 17α-hydroxyprogesterone caproate. All relevant abstracts were reviewed. For efficacy and safety data, the search was limited to randomized, double-blind, placebo-controlled trials with the primary outcome of preterm delivery, fetal loss, or neonatal morbidity or mortality. Quality of the studies was assessed using the CONSORT (Consolidated Standards of Reporting Trials) guidelines for reporting parallel-group randomized trials. Eleven articles were selected for review. Preterm birth, prior to 37 weeks' gestation, remains the leading cause of neonatal morbidity and mortality in the US due to lack of treatment options. Recently, the use of progesterone to prevent preterm labor, deemed decades ago to be ineffective, has been reexamined. Progesterone formulations and dosage regimens varied greatly between studies. In patients with prior preterm birth or shortened cervix shown on transvaginal ultrasound, progesterone appears efficacious in reducing the rate of preterm birth. However, this benefit was not demonstrated in multiple-gestation pregnancies. Overall, progesterone was well tolerated and appeared safe for mother and fetus. More studies are needed to confirm the dosage regimen and population that will benefit most from progesterone. Progesterone appears to be safe and efficacious in reducing the risk of preterm birth in a select group of high-risk women with prior spontaneous preterm births and those with an ultrasound-confirmed short cervix. Women with multiple gestations do not benefit from progesterone supplementation.

  11. Evidence that 17alpha-estradiol is biologically active in the uterine tissue: Antiuterotonic and antiuterotrophic action

    Directory of Open Access Journals (Sweden)

    Navarrete Erika

    2005-07-01

    Full Text Available Abstract Background 17alpha-Estradiol has been considered as the hormonally inactive isomer of 17beta-estradiol. Recently, nongenomic (smooth muscle relaxation and genomic (light estrogenic activity effects of 17alpha-estradiol have been reported, but no reports have yet determined its possible antiestrogenic activity. Therefore, this study investigated: the nongenomic action of 17alpha-estradiol on uterine contractile activity and its potential agonist-antagonist activity on uterine growth. Methods Uterine rings from rats were isometrically recorded. Different concentrations (0.2–200 microM of 17alpha-estradiol were tested on spontaneous contraction and equimolarly compared with 17beta-estradiol. To examine the mechanism of 17alpha-estradiol action, its effect was studied in presence of beta2-antagonist (propranolol, antiestrogens (tamoxifen and ICI 182,780 or inhibitors of protein synthesis (cycloheximide and transcription (actinomycin D. Moreover, contractions induced by high potassium (KCl solution or calcium in depolarized tissues by KCl-calcium free solution were exposed to 17alpha-estradiol. Collaterally, we performed an uterotrophic assay in adult ovariectomized rats measuring the uterine wet weight. The administration for three days of 0.3 microM/day/Kg 17beta-estradiol was equimolarly compared with the response produced by 17alpha-estradiol. Antiuterotrophic activity was assayed by administration of 0.3 microM/day/Kg 17beta-estradiol and various doses ratios (1:1, 1:3, 1:5, and 1:100 of 17alpha-estradiol. Results The estradiol isomers elicited an immediate relaxation, concentration-dependent and reversible on spontaneous contraction. 17alpha-Estradiol presented lower potency than 17beta-estradiol although it did not antagonize 17beta-estradiol-induced relaxation. Relaxation to 17alpha-estradiol was not inhibited by propranolol, tamoxifen, ICI 182,780, cycloheximide or actinomycin D. The KCl contractions were also sensitive to 17alpha

  12. Relationship between 17-hydroxyprogesterone caproate concentrations and gestational age at delivery in twin gestation.

    LENUS (Irish Health Repository)

    Caritis, Steve N

    2012-11-01

    We sought to evaluate in women with twin gestation the relationship between 17-hydroxyprogesterone caproate (17-OHPC) concentration and gestational age at delivery and select biomarkers of potential pathways of drug action.

  13. Progesterone supplementation and the prevention of preterm birth.

    Science.gov (United States)

    Norwitz, Errol R; Caughey, Aaron B

    2011-01-01

    Preterm birth is currently the most important problem in maternal-child health in the United States and possibly throughout the world. It complicates one in eight US deliveries, and accounts for over 85% of all perinatal morbidity and mortality. Although survival of preterm infants has increased steadily over the past four decades-due in large part to the use of antenatal corticosteroids, improvements in neonatal resuscitation, and the introduction of neonatal intensive care units-efforts to prevent preterm birth have been largely unsuccessful. On February 3, 2011, the US Food and Drug Administration (FDA) approved the use of progesterone supplementation (hydroxyprogesterone caproate) during pregnancy to reduce the risk of recurrent preterm birth in women with a history of at least one prior spontaneous preterm delivery. This is the first time that the FDA has approved a medication for the prevention of preterm birth, and represents the first approval of a drug specifically for use in pregnancy in almost 15 years. This article reviews the evidence behind the use of progesterone for the prevention of preterm birth, and provides guidelines for the use of progesterone supplementation in clinical practice. A number of areas of ongoing controversy are addressed, including the optimal formulation and route of administration, the safety of progesterone supplementation in pregnancy, and its proposed mode of action.

  14. Competitive and complementary adsorption of bisphenol A and 17alpha-ethinyl estradiol on carbon nanomaterials.

    Science.gov (United States)

    Pan, Bo; Xing, Baoshan

    2010-07-28

    Competitive adsorption between organic chemicals is an important process affecting their environmental behavior and risk. Overlapping of adsorption sites between solutes was often emphasized in the literature. However, chemicals with different properties may complementarily occupy different sorption sites. The objective of this study was to test this hypothesis by collecting detailed information on competitive and accumulative adsorption of different chemicals on carbon nanomaterials (CNMs). Bisphenol A (BPA) and 17alpha-ethinyl estradiol (EE2) are different with regard to their hydrophobicity and molecular structures, and they were selected as model chemicals. The cumulative adsorption of both BPA and EE2 in bisolute adsorption experiments resulted in much higher total adsorption than in single-solute adsorption experiments. A new competitive-complementary adsorption concept was proposed. This information indicates that the modeling concept of competitive adsorption should be improved to better understand the fate and risk of both CNMs and organic chemicals.

  15. Specific interactions of steroids, arylhydrocarbons and flavonoids with progesterone receptors from the cytosol of the fungus Rhizopus nigricans.

    Science.gov (United States)

    Lenasi, Helena; Breskvar, Katja

    2004-08-01

    Rhizopus nigricans (R. nigricans) transforms fungitoxic progesterone into the less toxic 11alpha-hydroxyprogesterone which is then able to exit the mycelia into the surrounding water. Hydroxylation of progesterone is an inducible process in which cytosolic progesterone receptors could be involved. In the present study, we characterised receptors with respect to ligand specificity and to their involvement in progesterone induction of hydroxylase. EC(50) values of different ligands (steroids, xenobiotic arylhydrocarbons and natural flavonoids) were determined by competition studies using 40nM ((3)H)progesterone. C21 and C19 3-oxo-4-ene steroids were good competitors (EC(50) of progesterone 2.3 +/- 0.1 x 10(-7)M, EC(50) of androsten-3,17-dione 24 +/- 2 x 10(-7)M). The presence of hydroxyl groups in steroids significantly decreased the affinity for receptors. The arylhydrocarbons alpha-naphthoflavone and ketoconazole exhibited EC(50) values of 0.3 +/- 0.01 x 10(-7)M and 27 +/- 5 x 10(-7)M, respectively, whereas beta-naphthoflavone and benzo(a)pyrene were not able to displace labelled progesterone completely. The competition curves obtained by natural flavonoids also did not reach the bottom level of non-labelled progesterone, indicating the interaction at some allosteric binding site(s) of progesterone receptors. All ligands were examined for their involvement in progesterone-hydroxylase induction. Steroid agonists induced the enzyme in a dose-dependent manner in accordance with their affinity for receptors, whereas arylhydrocarbons and natural flavonoids did not induce the enzyme. The agonistic action of steroids, together with the antagonistic action of alpha-naphthoflavone, strongly suggests the involvement of progesterone receptors in progesterone signalling resulting in the induction of progesterone-hydroxylase.

  16. The in vitro metabolism of 11β-hydroxyprogesterone and 11-ketoprogesterone to 11-ketodihydrotestosterone in the backdoor pathway.

    Science.gov (United States)

    van Rooyen, Desmaré; Gent, Rachelle; Barnard, Lise; Swart, Amanda C

    2017-12-23

    Increased circulating 11β-hydroxyprogesterone (11OHP4), biosynthesised in the human adrenal, is associated with 21-hydroxylase deficiency in congenital adrenal hyperplasia. 17α-hydroxyprogesterone levels are also increased, with the steroid's metabolism to dihydrotestosterone in the backdoor pathway contributing to hyperandrogenic clinical conditions. In this study we investigated the in vitro biosynthesis and downstream metabolism of 11OHP4. Both cytochrome P450 11β-hydroxylase and aldosterone synthase catalyse the biosynthesis of 11OHP4 from progesterone (P4) which is converted to 11-ketoprogesterone (11KP4) by 11β-hydroxysteroid dehydrogenase type 2, while type 1 readily catalysed the reverse reaction. We showed in HEK-293 cells that these C11-oxy C21 steroids were metabolised by steroidogenic enzymes in the backdoor pathway-5α-reductase (SRD5A) and 3α-hydroxysteroid type 3 (AKR1C2) converted 11OHP4 to 5α-pregnan-11β-ol,3,20-dione and 5α-pregnan-3α,11β-diol-20-one, while 11KP4 was converted to 5α-pregnan-3,11,20-trione and 5α-pregnan-3α-ol-11,20-dione (alfaxalone), respectively. Cytochrome P450 17α-hydroxylase/17,20-lyase catalysed the hydroxylase and lyase reaction to produce the C11-oxy C19 steroids demonstrated in the conversion of alfaxalone to 11-oxy steroids demonstrated in the conversion of alfaxalone to 11ketoandrosterone. In LNCaP cells, a prostate cancer cell model endogenously expressing the relevant enzymes, 11OHP4 and 11KP4 were metabolised to the potent androgen, 11-ketodihydrotestosterone (11KDHT), thus suggesting the C11-oxy C21 steroids contribute to the pool of validating the in vitro biosynthesis of C11-oxy C19 steroids from C11-oxy C21 steroids. The in vitro reduction of 11KP4 at C3 and C5 by AKR1C2 and SRD5A has confirmed the metabolic route of the urinary metabolite, 3α,20α-dihydroxy-5β-pregnan-11-one. Although our assays have demonstrated the conversion of 11OHP4 and 11KP4 by steroidogenic enzymes in the backdoor pathway

  17. Stainless Steel Sponge as a Carrier for Immobilization of Rhizopus nigricans Isolate used for Biotrnsformation of Progesterone to 11α-hydroxprogesterone

    OpenAIRE

    Ahmed, Essam M.

    2017-01-01

    Biotransformation is an important tool to provide the intermediate for steroid manufacturing. Stainless steel sponge was used as a carrier to immobilize an isolate of Rhizopus nigricans which can convert progesterone to 11α-hydroxyprogesterone (11α-HP). The conversion ability of the isolate was measured. The immobilized cells showed the ability to withstand the stress of the biotransformation process. Different parameters were studied to achieve the optimum conditions for 11α-HP production. T...

  18. Evaluation of factors associated with elevated newborn 17-hydroxyprogesterone levels.

    Science.gov (United States)

    Anandi, V Shobi; Shaila, Bhattacharyya

    2017-05-24

    Measurement of 17-hydroxyprogesterone (17-OHP) in dried blood spots has been widely used as a newborn screening tool for congenital adrenal hyperplasia (CAH). Various maternal and neonatal factors can result in falsely high values of 17-OHP. There is a paucity of Indian studies in this regard because routine evaluation of newborn 17-OHP levels as a screening program is not widely practiced in India. Hence, this study was undertaken to evaluate the influence of various maternal and neonatal factors on newborn 17-OHP levels. The aim of the study was to determine the effect of various maternal and neonatal factors on the newborn 17-OHP values. Retrospective data related to a total of 3080 newborn 17-OHP values and clinical characteristics were collected for 3 years (2013-2015). The data were analyzed to determine the influence of various factors on 17-OHP values. The mean value of 17-OHP in our study was 5.486±3.96 ng/mL. Gender and mode of delivery did not significantly affect the 17-OHP levels. The levels were significantly higher in preterm and low birth weight babies as compared to term babies and babies with normal birth weight. Stress factors like pregnancy induced hypertension (PIH), early onset sepsis (EOS), neonatal seizures and birth asphyxia significantly increase the neonatal 17-OHP levels. The levels of 17-OHP in newborns was measured around day 3 of life are very sensitive to the influence of gestational age, birth weight and presence of stress factors like maternal PIH, birth asphyxia, neonatal sepsis and neonatal seizures and should be interpreted cautiously.

  19. Immersion of fry in 17-Alpha Methyltestosterone can be highly effective for sex reversal in rainbow trout

    Science.gov (United States)

    17-alpha methyltestosterone (MT) is currently used to sex reverse genetic female rainbow trout into phenotypic males, commonly referred to as neomales. Neomales are primarily generated to propagate all-female lines. The MT is most commonly administered orally, fed during the first 6-9 weeks after sw...

  20. Chronic toxicity of the synthetic hormone 17alpha-ethinylestradiol to Chironomus tentans and Hyalella azteca.

    Science.gov (United States)

    Dussault, Eve B; Balakrishnan, Vimal K; Solomon, Keith R; Sibley, Paul K

    2008-12-01

    The chronic toxicity of the synthetic hormone 17alpha-ethinylestradiol (EE2) was investigated in two benthic invertebrates, the midge Chironomus tentans and the freshwater amphipod Hyalella azteca, in life-cycle water-only assays. In C. tentans, a 50% decrease in emergence was observed at a concentration of 1.5 mg/L; emergence was a more sensitive endpoint than survival, growth, or biomass. Reproduction was not significantly affected by EE2 exposure until a concentration of 3.1 mg/L, where emergence, and therefore reproduction, did not occur. In contrast, reproduction was the most sensitive endpoint in H. azteca (50% decrease in reproduction observed at a concentration of 0.36 mg/L). The sensitivity of the F1 generation to EE2 was also investigated with H. azteca, but was not different from the F0 generation. The data from the present study were combined with those from previous 10-d toxicity assays, to derive acute to chronic toxicity ratios (ACRs) for EE2. The ACRs calculated for EE2 were 13 for C. tentans and 16 for H. azteca, indicating that the application factors currently used in ecological risk assessment for the derivation of chronic toxicity are protective and conservative for these organisms. The results of the present study suggest that chronic toxicity was not mediated by disruption of endocrine pathways. Using a hazard quotient approach, the risk associated with sublethal exposure to EE2 was azteca and C. tentans, indicating that adverse effects are not expected, and that environmental exposure to EE2 likely poses a low risk to benthic invertebrates.

  1. Progesterone for premenstrual syndrome

    NARCIS (Netherlands)

    Ford, Olive; Lethaby, Anne; Roberts, Helen; Mol, Ben Willem J.

    2009-01-01

    BACKGROUND: About 5% of women experience severe symptoms called premenstrual syndrome (PMS), only in the two weeks before their menstrual periods. Treatment with progesterone may restore a deficiency, balance menstrual hormone levels or reduce effects of falling progesterone levels on the brain or

  2. Progesterone resistance in endometriosis

    DEFF Research Database (Denmark)

    Patel, Bansari G; Rudnicki, Martin; Yu, Jie

    2017-01-01

    Endometriosis is a common cause of pelvic pain and affects up to 10% of women of reproductive age. Aberrant progesterone signaling in the endometrium plays a significant role in impaired decidualization and establishment of ectopic endometrial implants. Eutopic endometrial cells from women...... renders infants susceptible to neonatal uterine bleeding and endometriosis. Progesterone action is crucial to decreasing inflammation in the endometrium, and deviant progesterone signaling results in a proinflammatory phenotype. Conversely, chronic inflammation can induce a progesterone resistant state...... and their targets. Environmental toxins, such as dioxin, play a possible role in the genesis of endometriosis by permitting an inflammatory milieu. A consequence of impaired progesterone action is that hormonal therapy is rendered ineffective for a subset of women with endometriosis. Synthetic progestins...

  3. Hepatic gene expression profiling using GeneChips in zebrafish exposed to 17{alpha}-methyldihydrotestosterone

    Energy Technology Data Exchange (ETDEWEB)

    Hoffmann, J.L.; Thomason, R.G.; Lee, D.M.; Brill, J.L.; Price, B.B.; Carr, G.J. [Miami Valley Innovation Center, Procter and Gamble Company, P.O. Box 538707, Cincinnati, OH 45253-8707 (United States); Versteeg, D.J. [Miami Valley Innovation Center, Procter and Gamble Company, P.O. Box 538707, Cincinnati, OH 45253-8707 (United States)], E-mail: versteeg.dj@pg.com

    2008-04-28

    Concentration and time-dependent changes in hepatic gene expression were examined in adult, female zebrafish (Danio rerio) exposed to 0, 0.1, 0.7, 4.9 {mu}g/L of a model androgen, 17{alpha}-methyldihydrotestosterone (MDHT). At 24 and 168 h, fish were sacrificed and liver was extracted for gene expression analysis using custom Affymetrix GeneChip Zebrafish Genome Microarrays. In an effort to link gene expression changes to higher levels of biological organization, blood was collected for measurement of plasma steroid hormones (17{beta}-estradiol (E2), testosterone (T)) and vitellogenin (VTG) using ELISA. Body and ovary weight were also measured. A significant reduction in E2 occurred at 24 h (0.7 and 4.9 {mu}g/L) and 168 h (4.9 {mu}g/L) following MDHT exposure. In contrast, T was significantly increased at 24 h (4.9 {mu}g/L) and 168 h (0.1, 0.7, 4.9 {mu}g/L). 171 and 575 genes were significantly affected in a concentration-dependent manner at either 24 or 168 h by MDHT exposure at p {<=} 0.001 and p {<=} 0.01, respectively. Genes involved in retinoic acid metabolism (e.g. aldehyde dehydrogenase 8, member A1; retinol dehydrogenase 12), steroid biosynthesis and metabolism (e.g. hydroxysteroid (11{beta}) dehydrogenase 2; hydroxy-delta-5-steroid dehydrogenase, 3 beta-), hormone transport (e.g. sex hormone binding globulin), and regulation of cell growth and proliferation (e.g. N-myc downstream regulated gene 1; spermidinespermine N(1)-acetyltransferase) were affected by MDHT exposure. In this study, we identified genes involved in a variety of biological processes that have the potential to be used as markers of exposure to androgenic substances. Genes identified in this study provide information on the potential mode of action of strong androgens in female fish. In addition, when used for screening of EDC's, these genes may also serve as sensitive markers of exposure to androgenic compounds.

  4. 17alpha/H/ hopane identified in oil shale of the Green River formation /Eocene/ by carbon-13 NMR.

    Science.gov (United States)

    Balogh, B.; Wilson, D. M.; Christiansen, P.; Burlingame, A. L.

    1973-01-01

    During an investigation of C-13 NMR shifts and the structural correspondence of pentacyclic triterpenes a C-13 NMR study was conducted on one of the most abundant components of the hexane soluble fraction of oil shale bitumen of the Green River formation. A rigorous proof was derived exclusively from C-13 NMR data for the structure of the important triterpenoid fossil molecule. It was established that the structure of the isolated triterpane was 17alpha(H) hopane.

  5. A randomised controlled double-blind clinical trial of 17-hydroxyprogesterone caproate for the prevention of preterm birth in twin gestation (PROGESTWIN): evidence for reduced neonatal morbidity.

    Science.gov (United States)

    Awwad, J; Usta, I M; Ghazeeri, G; Yacoub, N; Succar, J; Hayek, S; Saasouh, W; Nassar, A H

    2015-01-01

    To determine whether 17 alpha-hydroxyprogesterone caproate (17OHPC) prolongs gestation beyond 37 weeks of gestation (primary outcome) and reduces neonatal morbidity (secondary outcome) in twin pregnancy. Randomised controlled double-blind clinical trial. Tertiary-care university medical centre. Unselected women with twin pregnancies. Participants received weekly injections of 250 mg 17OHPC (n = 194) or placebo (n = 94), from 16-20 to 36 weeks of gestation. Randomisation was performed using the permuted-block randomisation method. Data were analysed on an intention-to-treat basis. Preterm birth (PTB) rate before 37 weeks of gestation. There were no significant differences in the average gestational age at delivery, or in the rates of PTB before 37, 32, and 28 weeks of gestation, between the two groups. The proportion of very-low-birthweight neonates (<1500 g) was significantly lower in the 17OHPC group (7.6%) compared with placebo (14.3%) (relative risk, RR 0.5; 95% confidence interval, 95% CI 0.3-0.9; P = 0.01). Progestogen-treated neonates had a significantly lower composite neonatal morbidity (19.1%) compared with placebo (30.9%) (odds ratio, OR 0.53; 95% CI 0.31-0.90; P = 0.02), with significantly lower odds for respiratory distress syndrome (14.4 versus 23.4%; OR 0.55; 95% CI 0.31-0.98; P = 0.04), retinopathy of prematurity (1.1 versus 4.6%; OR 0.21; 95% CI 0.05-0.96; P = 0.04), and culture-confirmed sepsis (3.4 versus 12.8%; OR 0.24; 95% CI 0.10-0.57; P = 0.00). Intramuscular 17OHPC therapy did not reduce PTB before 37 weeks of gestation in unselected twin pregnancies. Nonetheless, 17OHPC significantly reduced neonatal morbidity parameters and increased birthweight. © 2014 Royal College of Obstetricians and Gynaecologists.

  6. Second trimester cervical length and risk of preterm birth in women with twin gestations treated with 17-α hydroxyprogesterone caproate.

    LENUS (Irish Health Repository)

    Durnwald, Celeste P

    2010-12-01

    To compare rates of preterm birth before 35 weeks based on cervical length measurement at 16-20 weeks in women with twin gestations who received 17-α hydroxyprogesterone caproate (17OHPC) or placebo.

  7. Interrelationships among cortisol, 17-hydroxyprogesterone, and androstenendione exposures in the management of children with congenital adrenal hyperplasia.

    Science.gov (United States)

    Sarafoglou, Kyriakie; Zimmerman, Cheryl L; Gonzalez-Bolanos, Maria T; Willis, Brian A; Brundage, Richard

    2015-01-01

    Hydrocortisone is the standard replacement therapy for children with congenital adrenal hyperplasia (CAH). Relationships between cortisol exposures and pharmacodynamic responses of 17-hydroxyprogesterone and androstenedione exposures have not been systematically evaluated. (1) Assess individual oral hydrocortisone pharmacokinetics; (2) relate the observed cortisol exposure in each subject to the observed exposures of 17-hydroxyprogesterone and androstenedione; (3) determine potential individualized treatment regimens based on each subject's pharmacokinetic and pharmacodynamic parameters. Thirty-four patients (18 boys, 16 girls, aged 1.4 to 18.1 years) with CAH underwent 6-hour pharmacokinetic studies. Results were analyzed by noncompartmental methods to obtain the area under the curve (AUC) for cortisol, 17-hydroxyprogesterone, and androstenedione; maximum concentration and time-to-maximum concentration for cortisol; and minimum and time-to-minimum concentration for 17-hydroxyprogesterone and androstenedione. Mean (SD) cortisol half-life and Cmax were 1.01 (0.20) hours and 24.4 (5.4) μg/dL, respectively. The AUCs for cortisol, 17-hydroxyprogesterone and androstenedione were 40.8 (14.5) μg hour/dL, 29,490 (23,539) ng hour/dL, and 680 (795) ng hour/dL, respectively. No significant relationships existed between cortisol AUCs and the AUCs of either 17-hydroxyprogesterone (P=0.32) or androstenedione (P=0.99); nor were there differences between the change-from-baseline concentrations for cortisol with either 17-hydroxyprogesterone (P=0.80) or androstenedione (P=0.40). Cortisol simulations indicated that although four daily doses decreased 24-hour hypercortisolemia and hypocortisolemia, substantial periods of each remained. Concentration profiles of cortisol, 17-hydroxyprogesterone, and androstenedione are highly variable in children with CAH, and knowledge of them can assist in personalizing the therapy of CAH patients. Hydrocortisone's rapid half-life and the lack of

  8. Characterization of persistent follicles induced by prolonged treatment with progesterone in dairy cows: an experimental model for the study of ovarian follicular cysts.

    Science.gov (United States)

    Díaz, Pablo U; Stangaferro, Matías L; Gareis, Natalia C; Silvia, William J; Matiller, Valentina; Salvetti, Natalia R; Rey, Florencia; Barberis, Fabián; Cattaneo, Luciano; Ortega, Hugo H

    2015-10-15

    Cystic ovarian disease (COD) is a major factor contributing to poor reproductive efficiency of lactating dairy cows. The objective of the present study was to analyze the endocrine profile, growth dynamics, and histologic characteristics of persistent ovarian follicles-cysts developing in response to long-term administration of intermediate levels of progesterone. To this end, after synchronization of cows, a low dose of progesterone was administered for 5, 10, and 15 days after the expected day of ovulation in treated cows (groups P5, P10, and P15, respectively), using an intravaginal progesterone-releasing device. A significant increase in diameter was detected on Day 11 of progesterone treatment and thereafter (P cows and affected the basal concentration of LH. The pulse frequency remained high at 5 and 10 days of persistence and declined (P follicular persistence. Changes in the serum levels of estradiol, progesterone, 17-hydroxyprogesterone, and testosterone in serum and follicular fluid were also observed. In serum, estradiol increased gradually from proestrus to Day 10 of follicular persistence (P follicular persistence, 17-hydroxyprogesterone showed a significant decrease at 5 days of follicular persistence in relation to proestrus, and testosterone showed a significant increase (P follicular persistence. Correlation between serum and follicular fluid steroid concentrations was significant for testosterone (P ovarian cysts in COD are similar in many ways to the persistent follicles induced by progesterone, with an analogous hormonal and morphologic context, thus confirming a local role of subluteal levels of progesterone in COD pathogenesis and in the regulatory mechanisms of the ovarian function. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Membrane-bound progesterone receptors coupled to G proteins in the fungus Rhizopus nigricans.

    Science.gov (United States)

    Lenasi, Helena; Bavec, Aljosa; Zorko, Matjaz

    2002-07-16

    Steroid binding sites with high affinity for progesterone (Kd=40+/-14 nM determined by binding, and Kd=71+/-22 nM determined by displacement studies) and lower affinity for 21-hydroxyprogesterone and for testosterone, but no affinity for estradiol-17beta, onapristone and alpha-naphthoflavone were detected in the enriched plasma membrane fraction of the fungus Rhizopus nigricans. The amount of steroid binding sites is in accordance with the value of B(max)=744+/-151 fmol (mg protein)(-1). In the membrane fraction, progesterone induced about 30% activation of G proteins over basal level, as determined by GTPase activity (EC50=32+/-8 nM) and by the guanosine 5'-O-(3-thiotriphosphate) (GTPgammaS) binding rate (EC50=61+/-21 nM). The affinity of receptors for progesterone was substantially decreased in the presence of GTPgammaS and of cholera toxin. Our results suggest the existence of progesterone receptors in the membrane of Rhizopus nigricans and their coupling to G proteins.

  10. Decreased endogenous progesterone and ratio of progesterone to ...

    African Journals Online (AJOL)

    PRECIOUS

    2010-02-01

    Feb 1, 2010 ... Progesterone and estrogen are two steroid hormones whose exposure may decrease the risk and delay the onset of ischemic stroke. The main objective of this study was to determine the plasma level of progesterone, estrogen and ratio of progesterone/estrogen in ischemic stroke patients. The plasma.

  11. Decreased endogenous progesterone and ratio of progesterone to ...

    African Journals Online (AJOL)

    Progesterone and estrogen are two steroid hormones whose exposure may decrease the risk and delay the onset of ischemic stroke. The main objective of this study was to determine the plasma level of progesterone, estrogen and ratio of progesterone/estrogen in ischemic stroke patients. The plasma levels of ...

  12. Progesterone-dependent immunomodulation.

    Science.gov (United States)

    Szekeres-Bartho, J; Polgar, B; Kozma, N; Miko, E; Par, G; Szereday, L; Barakonyi, A; Palkovics, T; Papp, O; Varga, P

    2005-01-01

    The biological effects of progesterone are mediated by a 34-kDa protein named the progesterone-induced blocking factor (PIBF). PIBF, synthesized by lymphocytes of healthy pregnant women in the presence of progesterone, inhibits arachidonic acid release as well as NK activity, and modifies the cytokine balance. Within the cell the full-length PIBF is associated with the centrosome, while secretion of shorter forms is induced by activation of the cell. PIBF induces nuclear translocation of STAT6 as well as PKC phosphorylation and exerts a negative effect on STAT4 phosphorylation. The concentration of PIBF in pregnancy urine is related to the positive or negative outcome of pregnancy; furthermore, premature pregnancy termination is predictable by lower than normal pregnancy PIBF values. In vivo data suggest the biological importance of the above findings. Treatment of pregnant Balb/c mice with the antiprogesterone RU 486 results in an increased resorption rate, which is associated with the inability of spleen cells to produce PIBF. High resorption rates induced by progesterone receptor block as well as those due to high NK activity are corrected by simultaneous PIBF treatment.

  13. The effect of pimozide/LHRHa and 17α-hydroxyprogesterone on plasma steroid levels and ovulation in the African catfish, Clarias gariepinus

    NARCIS (Netherlands)

    Richter, C.J.J.; Eding, E.H.; Goos, H.J.Th.; Leeuw, R. de; Scott, A.P.; Oordt, P.G.W.J. van

    1987-01-01

    The effect was studied of a preovulatory gonadotropic hormone (GTH) surge, induced by pimozide/LHRHa treatment, and of 17α-hydroxyprogesterone on oocyte maturation and ovulation and on the plasma levels of 17α-hydroxyprogesterone, 17α-hydroxy-20β-dihydroprogesterone, testosterone and estradiol. GTH

  14. Progesterone as an immunomodulatory molecule.

    Science.gov (United States)

    Szekeres-Bartho, J; Barakonyi, A; Par, G; Polgar, B; Palkovics, T; Szereday, L

    2001-06-01

    Increased progesterone sensitivity of pregnancy lymphocytes is due to activation-induced appearance of progesterone binding sites in the lymphocytes. Following recognition of fetally derived antigens gamma/delta TCR+ cells develop progesterone receptors. Progesterone binding results in the synthesis of a mediator protein named the progesterone-induced blocking factor (PIBF). PIBF by acting on the phospholipase A2 enzyme interferes with arachidonic acid metabolism, induces a Th2 biased immune response, and by controlling NK activity exerts an anti-abortive effect.

  15. Short-term exposure to 17alpha-ethynylestradiol decreases the fertility of sexually maturing male rainbow trout (Oncorhynchus mykiss)

    Energy Technology Data Exchange (ETDEWEB)

    Schultz, Irv R.; Skillman, Ann D.; Nicolas, Jean-Marc; Cyr, Daniel G.; Nagler, James J.

    2003-06-01

    The synthetic estrogen 17alpha-ethynylestradiol (EE2) is a commonly used oral contraceptive that has been increasingly detected in sewage effluents. This study determined whether EE2 exposure adversely affected reproduction in sexually maturing male rainbow trout (Oncorhynchus mykiss). We exposed male trout to graded water concentrations of EE2 (10, 100, and 1,000 ng/ L) for 62 d leading up to the time of spawning. Semen and blood plasma samples were removed from each fish. Semen was used to fertilize groups of eggs from one nonexposed female. As a measure of fertility, eggs were incubated for 28 d after fertilization to determine the proportion that attained the eyed stage of embryonic development. Additional endpoints also measured included sperm motility, spermatocrit, gonadosomatic and hepatosomatic indices, testis histology, and circulating plasma levels of the sex steroids 17alpha, 20beta-dihydroxyprogesterone (17,20-DHP) and 11-ketotestosterone (11-KT). Exposure to 1,000 ng/L of EE2 caused complete mortality of the treatment group by day 57. Exposure to lower EE2 water concentrations (10 and 100 ng/L) caused an increase in sperm density, while a significant reduction in testis mass was observed only in the 100-ng/L exposure group. Most significantly, semen harvested from fish exposed to 10 and 100 ng/L EE2 caused an approximately 50% reduction in the number of eggs attaining the eyed stage of embryonic development. Plasma levels of 17,20-DHP in exposed fish were roughly twice the level of the controls, while levels of 11-KT were significantly reduced in fish exposed to 100 ng/L EE2. These results suggest that sexually maturing male rainbow trout are susceptible to detrimental reproductive effects of short-term exposures to environmentally relevant levels of EE2.

  16. Progesterone and preterm birth prevention: translating clinical trials data into clinical practice.

    Science.gov (United States)

    2012-05-01

    We sought to provide evidence-based guidelines for using progestogens for the prevention of preterm birth (PTB). Relevant documents, in particular randomized trials, were identified using PubMed (US National Library of Medicine, 1983 through February 2012) publications, written in English, which evaluate the effectiveness of progestogens for prevention of PTB. Progestogens evaluated were, in particular, vaginal progesterone and 17-alpha-hydroxy-progesterone caproate. Additionally, the Cochrane Library, organizational guidelines, and studies identified through review of the above were utilized to identify relevant articles. Data were evaluated according to population studied, with separate analyses for singleton vs multiple gestations, prior PTB, or short transvaginal ultrasound cervical length (CL), and combinations of these factors. Consistent with US Preventive Task Force suggestions, references were evaluated for quality based on the highest level of evidence, and recommendations were graded. Summary of randomized studies indicates that in women with singleton gestations, no prior PTB, and short CL ≤ 20 mm at ≤ 24 weeks, vaginal progesterone, either 90-mg gel or 200-mg suppository, is associated with reduction in PTB and perinatal morbidity and mortality, and can be offered in these cases. The issue of universal CL screening of singleton gestations without prior PTB for the prevention of PTB remains an object of debate. CL screening in singleton gestations without prior PTB cannot yet be universally mandated. Nonetheless, implementation of such a screening strategy can be viewed as reasonable, and can be considered by individual practitioners, following strict guidelines. In singleton gestations with prior PTB 20-36 6/7 weeks, 17-alpha-hydroxy-progesterone caproate 250 mg intramuscularly weekly, preferably starting at 16-20 weeks until 36 weeks, is recommended. In these women with prior PTB, if the transvaginal ultrasound CL shortens to premature rupture of

  17. Sorption of acetaminophen, 17alpha-ethynyl estradiol, nalidixic acid, and norfloxacin to silica, alumina. and a hydrophobic medium.

    Science.gov (United States)

    Lorphensri, Oranuj; Intravijit, Jittipong; Sabatini, David A; Kibbey, Tohren C G; Osathaphan, Khemarath; Saiwan, Chintana

    2006-04-01

    Two pure minerals and a hydrophobic medium were selected to study sorption of pharmaceuticals. The sorption of four pharmaceuticals, acetaminophen (analgesic), 17alpha-ethynyl estradiol (synthetic hormone), nalidixic acid (antibiotic), and norfloxacin (antibiotic), was evaluated with silica, alumina, and Porapak P (a hydrophobic medium). Alumina and silica were selected to represent positively charged and negatively charged aquifer mineral surfaces at neutral pH, respectively, while Porapak P was selected to represent the hydrophobic organic content of an aquifer medium. At neutral pH, acetaminophen, the least hydrophobic pharmaceutical, showed no significant sorption to any of the media, while 17alpha-ethynyl estradiol, the most hydrophobic pharmaceutical, showed significant sorption to Porapak P. Nalidixic acid, which has a carboxyl functional group that is anionic at neutral pH, showed significant adsorption to the positively charged alumina. Norfloxacin, with both a carboxyl (anionic) and a piperazynyl (cationic) group, can exist in four forms (neutral, cationic, anionic, and zwitterionic) depending on the aqueous pH. Norfloxacin also showed significant adsorption than nalidixic acid. Both nalidixic acid and norfloxacin adsorbed to silica and Porapak P to a much lower extent. The pH dependence of nalidixic acid and norfloxacin adsorption to silica and alumina was also studied by varying the pH between 4 and 11. The maximum adsorption of nalidixic acid to alumina occurred near its pKa (pH approximately 6), where the combination of cationic alumina and anionic nalidixic produced maximum adsorption. The maximum adsorption of norfloxacin to alumina was observed at pH approximately 7, which was the region where the zwitterionic form dominated. This research demonstrates that the adsorption of ionizable pharmaceuticals is strongly dependent on the system pH, the pharmaceutical properties (pKa and hydrophobicity), and the nature of the surface charge (point of zero

  18. Bioaccumulation of the pharmaceutical 17{alpha}-ethinylestradiol in shorthead redhorse suckers (Moxostoma macrolepidotum) from the St. Clair River, Canada

    Energy Technology Data Exchange (ETDEWEB)

    Al-Ansari, Ahmed M.; Saleem, Ammar; Kimpe, Linda E. [University of Ottawa, Department of Biology, Chemical and Environmental Toxicology, Ottawa, Ontario K1N 6N5 (Canada); Sherry, Jim P.; McMaster, Mark E. [Environment Canada, Water Science and Technology Directorate, Canada Centre for Inland Waters, Burlington, Ontario (Canada); Trudeau, Vance L. [University of Ottawa, Department of Biology, Chemical and Environmental Toxicology, Ottawa, Ontario K1N 6N5 (Canada); Blais, Jules M., E-mail: jules.blais@uottawa.c [University of Ottawa, Department of Biology, Chemical and Environmental Toxicology, Ottawa, Ontario K1N 6N5 (Canada)

    2010-08-15

    17{alpha}-ethynylestradiol (EE2), a synthetic estrogen prescribed as a contraceptive, was measured in Shorthead Redhorse Suckers (ShRHSs) (Moxostoma macrolepidotum) collected near a wastewater treatment plant (WWTP) in the St. Clair River (Ontario, Canada). We detected EE2 in 50% of the fish samples caught near the WWTP (Stag Island), which averaged 1.6 {+-} 0.6 ng/g (wet weight) in males and 1.43 {+-} 0.96 ng/g in females. No EE2 was detected in the samples from the reference site (Port Lambton) which was 26 km further downstream of the Stag Island site. Only males from Stag Island had VTG induction, suggesting the Corunna WWTP effluent as a likely source of environmental estrogen. EE2 concentrations were correlated with total body lipid content (R{sup 2} = 0.512, p < 0.01, n = 10). Lipid normalized EE2 concentrations were correlated with {delta}{sup 15}N (R{sup 2} = 0.436, p < 0.05, n = 10), suggesting higher EE2 exposures in carnivores. Our data support the hypothesis of EE2 bioaccumulation in wild fish. - Ethinylestradiol accumulation in wild fish.

  19. Mutation R96W in cytochrome P450c17 gene causes combined 17{alpha}-hydroxylase/17-20-lyase deficiency in two french canadian patients

    Energy Technology Data Exchange (ETDEWEB)

    LaFlamme, N.; Leblanc, J.F.; Mailloux, J. [Laval Univ., Quebec (Canada)

    1996-01-01

    Congenital adrenal hyperplasia (CAH) is the most frequent cause of adrenal insufficiency and ambiguous genitalia in newborn children. In contrast to CAH caused by 21{alpha}-hydroxylase and 11{beta}-hydroxylase deficiencies, which impairs steroid formation in the adrenal exclusively, 17{alpha}-hydroxylase/17,20-lyase deficiency impairs steroid biosynthesis in the adrenals and gonads. The sequence of CYP17 gene was determined by direct sequencing of asymmetric PCR products in two French-Canadian 46,XY pseudohermaphrodite siblings suffering from combined 17{alpha}-hydroxylase/17,20-lyase deficiency. The two patients are homozygous for the novel missense mutation R96W caused by a C to T transition converting codon Arg{sup 96} (CGG) into a Trp (TGG) in exon 1. Both parents are heterozygous for this missense mutation. We assessed the effect of the R96W mutation on 17{alpha}-hydroxylase/17,20-lyase activity by analysis of mutant enzyme, generated by site-directed mutagenesis, expressed in COS-1 cells. The presence of R96W substitution almost completely abolished the activity of the mutant protein. The present findings provide a molecular explanation for the signs and symptoms of combined 17 {alpha}-hydroxylase/17,20-lyase deficiency in these two patients and provide useful information on the structure-activity relationships of the P450c17 enzyme. 31 refs., 4 figs., 1 tab.

  20. Bioaccumulation of the synthetic hormone 17alpha-ethinylestradiol in the benthic invertebrates Chironomus tentans and Hyalella azteca.

    Science.gov (United States)

    Dussault, Eve B; Balakrishnan, Vimal K; Borgmann, Uwe; Solomon, Keith R; Sibley, Paul K

    2009-09-01

    The present study investigated the bioaccumulation of the synthetic hormone 17alpha-ethinylestradiol (EE2) in the benthic invertebrates Chironomus tentans and Hyalella azteca, in water-only and spiked sediment assays. Water and sediment residue analysis was performed by LC/MS-MS, while biota extracts were analyzed using both LC/MS-MS and a recombinant yeast estrogen receptor assay. At the lowest exposure concentration, C. tentans accumulated less EE2 than H. azteca in the water-only assays (p=0.0004), but due to different slopes, this difference subsided with increasing concentrations; at the exposure concentration of 1mg/L, C. tentans had a greater body burden than H. azteca (p=0.02). In spiked sediments, C. tentans had the greatest EE2 accumulation (1.2+/-0.14 vs. 0.5+/-0.05 microg/gdw, n=4). Measurements in H. azteca indicated a negligible contribution from the sediments to the uptake of EE2 in this species. These differences were likely due to differences in the behavior and life history of the two species (epibenthic vs. endobenthic). Water-only bioaccumulation factors (BAFs) calculated at the lowest exposure concentration were significantly smaller in C. tentans than in H. azteca (31 vs. 142, respectively; pazteca (0.8 vs. 0.3; p<0.0001). Extracts of the exposed animals caused a response in a recombinant yeast estrogen receptor assay, thus confirming the estrogenic activity of the samples, presumably from EE2 and its estrogenic metabolites. The results of the present study suggest that consumption of invertebrate food items could provide an additional source of exposure to estrogenic substances in vertebrate predators.

  1. Quantification of Dehydroepiandrosterone, 11-Deoxycortisol, 17-Hydroxyprogesterone, and Testosterone by Liquid Chromatography-Tandem Mass Spectrometry (LC/MS/MS).

    Science.gov (United States)

    Munar, Ada; Frazee, Clint; Garg, Uttam

    2016-01-01

    Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders due to enzymatic defects in the biosynthetic pathway of cortisol and/or aldosterone. The analysis of cortisol, 17-hydroxyprogesterone (OHPG), dehydroepiandrosterone (DHEA), 11-deoxycortisol, and testosterone is generally performed in the diagnosis and/or follow-up of CAH. Cortisol is generally analyzed by immunoassays whereas other hormones are preferably assayed by liquid chromatography-tandem mass spectrometry (LC/MS/MS). A multiple reaction monitoring, positive mode atmospheric pressure chemical ionization, LC/MS/MS method is described for the simultaneous quantification of 17-hydroxyprogesterone, DHEA, 11-deoxycortisol, and testosterone. Stable-isotope labeled internal standards are added to serum samples and steroids are extracted by liquid-liquid extraction using methyl tert-butyl ether. The extract is evaporated under stream of nitrogen and the residue is reconstituted in methanol and analyzed by LC/MS/MS.

  2. The Influence of Prior Obstetrical History on Current 17-Hydroxyprogesterone Caproate Use

    Directory of Open Access Journals (Sweden)

    Carla E. Ransom

    2011-01-01

    Full Text Available Objective. To determine if gestational age of prior preterm delivery influences a woman's receipt of 17-hydroxyprogesterone caproate (17-OHP-C. Methods. Retrospective cohort of women eligible for 17-OHP-C at Duke Obstetrics Clinic were identified by medical record review. Sociodemographic and clinical characteristics were abstracted. Results. Of 104 eligible subjects, 82 (78.8% were offered 17-OHP-C. Of these, thirty-four (41.5% declined. The median gestational age of the most recent preterm delivery was significantly lower among subjects who accepted 17-OHP-C as compared to those who declined (28.7 vs. 34.0 weeks, =.02 and in subjects offered 17-OHP-C compared to those not offered 17-OHP-C (30.2 vs. 36.0 weeks, =.03. Subjects not offered 17-OHP-C were more likely to have had an interval term delivery (31.8% vs. 9.7%, =.009 Conclusion. Women with earlier preterm deliveries were more likely to be offered and accept 17-OHP-C. Prior obstetric history may influence both providers' and patients' willingness to discuss and/or accept 17-OHP-C.

  3. Overview of progesterone profiles in dairy cows

    DEFF Research Database (Denmark)

    Blavy, P.; Derks, M.; Martin, O.

    2016-01-01

    kernel of three data points was used to smooth the progesterone time series. The time between start of progesterone rise and end of progesterone decline was identified by fitting a simple model consisting of base length and a quadratic curve to progesterone data, and this luteal like phase (LLP) was used...... to classify progesterone profiles without recourse to an a priori set of rules, which arbitrarily segment the natural variability in these profiles. Using data-derived profile shapes may allow a more accurate assessment of the effects of for example nutritional management or breeding system on progesterone...

  4. Elevated progesterone during ovarian stimulation for IVF

    DEFF Research Database (Denmark)

    Al-Azemi, M; Kyrou, D; Kolibianakis, E M

    2012-01-01

    There is an ongoing debate regarding the impact of premature progesterone rise on the IVF outcome. The objective of this review is to assess evidence of poorer ongoing pregnancy rate in IVF cycles with elevated serum progesterone at the end of follicular phase in ovarian stimulation. It also...... of premature progesterone in stimulated IVF cycles. There is an ongoing debate regarding the impact of premature progesterone rise on the IVF outcome. The objective of this review is to assess evidence of poorer ongoing pregnancy rate in IVF cycles with elevated serum progesterone at the end of follicular...... should document the cause and origin of premature progesterone in stimulated IVF cycles....

  5. The dialectic role of progesterone.

    Science.gov (United States)

    Huber, Johannes C; Ott, Johannes

    2009-04-20

    Progesterone is known to be metabolized into various metabolites exerting various effects, predominantly into 5alpha-pregnanes and 4-pregnenes. Studies on uterine tissues showed numerous progesterone-converting enzymes such as 5alpha-reductase (5alphaR), 5beta-reductase, 3alpha-, 3beta-, 20alpha-, and 20beta-hydroxysteroid oxidoreductases and others. The main progesterone-metabolizing enzymes in human breast tissues are 5alphaR, 3alpha-HSO 3beta-HSO, and 20alpha-HSO. Tumor genesis in the breast has been shown to be enhanced by high 5alphaR activity and suppression of 3alpha-HSO and 20alpha-HSO. A major determinant of 5alphaR, the breast's gate-keeping enzyme activity is the genetic variation in the enzyme's gene. Two polymorphisms within the steroid 5alphaR type 2 gene, Ala>Thr at codon 49 and Val>Leu at codon 89 have been reported to strongly affect the enzyme's activity, even in regard to breast cancer risk. As steroid hormones are known to be converted into many other steroids occupying different receptors and thereby exerting various different effects, progesterone receptors are important factors when mediating the hormone's effects. The progesterone receptor (PR) gene is transcribed from one gene by two alternative promoters and translated into PR-B, a potent transcriptional activator, and PR-A, the shorter isoform, necessary to oppose the effects of PR-B. In addition, endocrine reactions are modulated by epigenetics. The expression of progesterone receptors has been shown to be up- and downregulated by various epigenetic mechanisms. Many factors must be also taken into account in hormonal (replacement) therapy. Thus natural steroids should not be disparaged as treatment options for gender-specific diseases. An update on endocrinological knowledge and experience is rather mandatory for gynaecologists.

  6. Assay for trenbolone and its metabolite 17 alpha-trenbolone in bovine urine based on immunoaffinity chromatographic clean-up and off-line high-performance liquid chromatography-thin-layer chromatography.

    Science.gov (United States)

    van Ginkel, L A; van Blitterswijk, H; Zoontjes, P W; van den Bosch, D; Stephany, R W

    1988-07-22

    An high-performance liquid chromatography (HPLC)-thin-layer chromatography (TLC) method was developed to detect the illegal use of the xenobiotic growth promotor Trenbolone acetate (TBA). Very effective clean-up of bovine urine was achieved by immunoaffinity chromatography (IAC). The active form of TBA, the steroid 17 beta-Trenbolone (17 beta-TB), as well as its major metabolite 17 alpha-Trenbolone (17 alpha-TB), were assayed simultaneously with HPLC and on-line UV detection. The fraction containing 17 alpha-TB and 17 beta-TB (TB-fraction) was collected, and for confirmation 17 beta- and 17 alpha-TB were subsequently separated and identified by TLC. The limit of detection by on-line HPLC-UV (350 nm) was 1-2 micrograms TB/l. Off-line TLC detection was even more sensitive, 0.5 microgram 17 beta- or 17 alpha-TB/1. The assay was validated by investigating urine samples from veal calves implanted with TBA. The presence of 17 beta- and 17 alpha-TB was clearly demonstrated. A survey of the illegal use of TBA in cattle was performed by applying the assay to urine obtained at slaughter. No residues of TBA or its metabolites were found in any of the 144 random samples from the Dutch public health surveillance programme.

  7. [Effect of water quality on degradation of 17alpha-ethynyestradiol (EE2) by UV/H2O2 combination process].

    Science.gov (United States)

    Li, Qing-song; Gao, Nai-yun; Ma, Xiao-yan; Wang, Li; Zhao, Jian-fu; Le, Lin-sheng

    2006-10-01

    Effect of pH, HA and anions HCO3-, NO3-, CO3(2-), Cl- and SO4(2-) in aqueous solution on the photodegradation of 17alpha-ethynyestradiol (EE2) was studied by using a batch photo-reactor. The results show that 17alpha-ethynyestradiol (EE2) could be removed effectively by the UV/H2O2 process. The rate of photodegradation in aqueous solution follows first-order kinetics. When H2O2 was dosed as 5 mg/L, irradiated by a 14W low pressure mercury vapor discharge lamp, the first-order photodegradation rate constant of EE2 in distilled water and tap water were 0.0630 min(-1) and 0.1324 min(-1) respectively. HA, HCO3-, NO3-, Cl- and SO4(2-) have inhibitory action on EE2 photodegradation. When their concentrations at 5 mmol/L, their inhibitory action: HCO3- > SO4(2-) > Cl- > NO3-. HCO3- induced photodegradation rate constant of EE2 reduced by half, It was anions synthesize effect that caused photodegradation rate constant of EE2 in tap water lower than distilled water.

  8. [Progesterone and prevention of preterm birth].

    Science.gov (United States)

    Fuchs, F; Senat, M-V

    2015-10-01

    The literature confirms the interest of progesterone for prevention of preterm delivery in specific indications for patients carrying a singleton pregnancy. In contrast, randomized trials have shown no benefit using progesterone in the prevention of prematurity in twins and even an adverse effect. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  9. PROGESTERONE: BIOSYNTHESIS FROM PREGNENOLONE IN HOLARRHENA FLORIBUNDA.

    Science.gov (United States)

    BENNETT, R D; HEFTMANN, E

    1965-08-06

    After administration of pregnenolone-4-C(14) to Holarrhena floribunda leaves, radioactive progesterone was isolated and purified to constant specific activity by chromatography, conversion to a derivative, and recrystallization. The result suggests that the biogenetic sequence leading to progesterone is the same in plants as in animals.

  10. [Effects of ursodeoxycholic acid on the liver plasma membrane fluidity, hepatic glutathione concentration, hepatic estrogen receptors and progesterone receptors in pregnant rats with ethinylestradiol and progesterone induced intrahepatic cholestasis].

    Science.gov (United States)

    Shi, Qing-yun; Kong, Bei-hua; Ma, Kai-dong; Zhang, Xiang-li; Jiang, Sen

    2003-11-01

    To explore the effects of ursodeoxycholic acid (UDCA) on the fluidity of hepatic plasma membrane, glutathione concentration in liver, hepatic estrogen receptors and progesterone receptors in pregnant rats with ethinylestradiol and progesterone induced intrahepatic cholestasis. sixty clean SD pregnant rats were selected and divided into three groups at random. Since the 13th day of pregnancy after taking blood, normal group was injected subcutaneously with refined vegetable oil 2.5 ml x kg(-1) x d(-1). Control group and treatment group were injected subcutaneously with the solution of progesterone 75 mg x kg(-1) x d(-1) and 17-alpha-ethynylestradio 1.25 mg x kg(-1) x d(-1) till the 17th day. Since the 17th day control group, normal group were fedwish 0.9% natriichloridi solution 5 ml x kg(-1) x d(-1); Treatment group was fedwish UDCA 50 mg x kg(-1) x d(-1) every day. On the 21th day, all rats were killed. Then the livers were collected for study. Membrane fluidity was measured by fluorescence polarization using 1,6-diphenyl-1,3,5-hexatriene (DPH) as a probe. Glutathione concentration was measured by 5,5'-dithionbis (2-nitrobenzoic acid) (DTNB). Estrogen receptors and progesterone receptors were measured by flow cytometry. (1) Hepatic plasma membrane fluidity and glutathione (GSH) concentration: significantly lower level of GSH concentration and higher fluorescence polarization (P) were detected in control group (GSH: 1.13 +/- 0.03, P: 0.149 +/- 0.008) in comparison with normal group (GSH: 2.11 +/- 0.07, P: 0.132 +/- 0.004, P 0.05). Ursodeoxycholic acid may be effective drug in treatment intrahepatic cholestasis of pregnancy.

  11. Estrogen and progesterone receptors in gynecomastia.

    Science.gov (United States)

    Pensler, J M; Silverman, B L; Sanghavi, J; Goolsby, C; Speck, G; Brizio-Molteni, L; Molteni, A

    2000-10-01

    The etiology of gynecomastia is unknown. There seems to be no increased incidence of malignancies in patients with idiopathic gynecomastia; however, patients with Klinefelter syndrome exhibit an increased incidence of malignancy. The authors reviewed the results of 34 patients with gynecomastia diagnosed in adolescence who, following initial evaluation, had a mastectomy. The estrogen and progesterone receptors were analyzed in these patients. Three of the patients were diagnosed with Klinefelter syndrome. These three patients exhibited elevated amounts of estrogen and progesterone receptors. None of the patients who were not diagnosed with this syndrome demonstrated significant elevation of their estrogen or progesterone receptors. The presence of elevated estrogen and progesterone receptors in patients with Klinefelter syndrome provides a potential mechanism by which these patients may develop breast neoplasms. The absence of elevated estrogen and progesterone receptors in patients with idiopathic gynecomastia may serve to clarify why these patients' disease rarely degenerates into malignancy.

  12. Autoimmune Progesterone Dermatitis: A Case Report

    Directory of Open Access Journals (Sweden)

    Rachana George

    2012-01-01

    Full Text Available Background. Autoimmune progesterone dermatitis is a rare cyclic premenstrual allergic reaction to progesterone produced during the luteal phase of a woman's menstrual cycle. Patients present with a variety of conditions including erythema multiforme, eczema, urticaria, angioedema, and progesterone-induced anaphylaxis. Case. Thirty-eight-year-old woman G2P2002 presents with erythema multiforme and urticarial rash one week prior to her menses starting one year after menarche. She was treated with oral contraceptive pills and the symptoms resolved. Conclusion. This is a typical case of progesterone autoimmunity. The diagnosis is based on cyclic nature of the dermatitis. This differentiates the condition from other allergies or systemic diseases with skin manifestations. Inhibition of ovulation in such cases results in decrease in progesterone secretion and prevention of symptoms.

  13. Determination of the hormonal growth promoter 17alpha-methyltestosterone in food-producing animals: bovine hair analysis by HPLC-MS/MS.

    Science.gov (United States)

    Regal, P; Nebot, C; Vázquez, B I; Cepeda, A; Fente, C A

    2010-01-01

    This paper describes the development, validation and application of a confirmatory method to detect 17alpha-methyltestosterone (MT) in bovine hair, to aid in controlling the administration of this growth promoter in meat-producing animals. After cryogenic grinding, MT was removed from the hair matrix using a single step extraction procedure with acetonitrile. Hydroxylamine derivatisation was used to enhance analyte determination with an electrospray ionisation (ESI) source. Determination was carried out using a triple quadrupole liquid chromatography tandem mass spectrometer (LC-MS/MS) in multiple reaction monitoring mode (MRM). The method was validated in accordance with the criteria defined in Commission Decision 2002/657/EC and using deuterated testosterone (T-d(3)) as the internal standard. The decision limit (CCalpha) was 0.07 ng g(-1) and the detection capability (CCbeta) was 0.12 ng g(-1). Repeatability was CV% (7%), within-laboratory reproducibility was CV% (11.0%), and trueness was (87%). Applicability of the method was demonstrated in an animal study. Samples obtained from animal experiments were analyzed and the presence of MT was confirmed.

  14. Effects of eutrophication on vitellogenin gene expression in male fathead minnows (Pimephales promelas) exposed to 17{alpha}-ethynylestradiol in field mesocosms

    Energy Technology Data Exchange (ETDEWEB)

    Gordon, Denise A. [Molecular Indicators Research Branch, Ecological Exposure Research Division, National Exposure Research Laboratory, Office of Research and Development, United States Environmental Protection Agency, 26 West Martin L. King Dr., m/s 642, Cincinnati, OH 45268 (United States); Toth, Gregory P. [Molecular Indicators Research Branch, Ecological Exposure Research Division, National Exposure Research Laboratory, Office of Research and Development, United States Environmental Protection Agency, 26 West Martin L. King Dr., m/s 642, Cincinnati, OH 45268 (United States); Graham, David W. [Department of Civil, Environmental and Architectural Engineering, University of Kansas, 4112 Learned Hall, Lawrence, KS 60045 (United States)]. E-mail: dwgraham@ku.edu; Lazorchak, James M.; Reddy, Tirumuru V. [Molecular Indicators Research Branch, Ecological Exposure Research Division, National Exposure Research Laboratory, Office of Research and Development, United States Environmental Protection Agency, 26 West Martin L. King Dr., m/s 642, Cincinnati, OH 45268 (United States); Knapp, Charles W. [Department of Civil, Environmental and Architectural Engineering, University of Kansas, 4112 Learned Hall, Lawrence, KS 60045 (United States); Noyelles, Frank de; Campbell, Scott [Kansas Biological Survey, University of Kansas, Foley Hall, 2021 Constant Avenue, Lawrence, KS 66047 (United States); Lattier, David L. [Molecular Indicators Research Branch, Ecological Exposure Research Division, National Exposure Research Laboratory, Office of Research and Development, United States Environmental Protection Agency, 26 West Martin L. King Dr., m/s 642, Cincinnati, OH 45268 (United States)]. E-mail: lattier.david@epa.gov

    2006-08-15

    This study evaluated the effect of aquatic secondary nutrient supply levels (nitrogen and phosphorus) on the subcellular response of adult male fathead minnows (Pimephales promelas) exposed to a single nominal concentration of 17{alpha}-ethynylestradiol (EE2), a potent synthetic estrogen, under quasi-natural field conditions. Outdoor mesocosms were maintained under low, medium, and high nutrient supply conditions as categorized by total phosphorus (TP) level (nominal 0.012, 0.025, and 0.045 mg TP/L, respectively), and treated with EE2 with and without a carrier solvent. Using reverse transcription-polymerase chain reaction methods, vitellogenin gene (Vg) expression was determined in the fish collected at 0 h, 8 h, 24 h, 4 d, 7 d, and 14 d post-exposure. Induction of Vg was detected as early as 8 h post-exposure, with and without the carrier solvent, and persisted through Day 14. Results showed Vg to be significantly greater at low nutrient levels (p < 0.05), suggesting that EE2 bioavailability to the fish was likely greater under less-turbid water conditions. - Nutrient condition in surface waters strongly influences vitellogenin gene expression in male fathead minnows.

  15. Exposure of the eggs to 17{alpha}-methyl testosterone reduced hatching success and growth and elicited teratogenic effects in postembryonic life stages of crayfish

    Energy Technology Data Exchange (ETDEWEB)

    Vogt, Guenter [Zoological Institute and Museum, University of Greifswald, Johann-Sebastian-Bach-Strasse 11/12, D-17487 Greifswald (Germany)], E-mail: gunter.vogt@web.de

    2007-12-30

    Testosterone is regularly found in the tissues of decapod crustaceans. Although this vertebrate-type sex hormone is not the principal factor of sex differentiation in crustaceans, it was shown to be capable of acting on the reproductive organs of shrimps and crabs. In the present study I have exposed developing eggs and stage 5 juveniles of the parthenogenetic all female marbled crayfish to 17{alpha}-methyl testosterone in order to test whether in freshwater crayfish sex can be changed from female to male by this androgen. MT did not elicit sex change, neither when administered during embryonic development nor during juvenile stage 5, the main period of proliferation of the oocytes. However, exposure to 100 {mu}g/L MT from 64% to 84% embryonic development resulted in prolonged embryonic development, reduced hatching success, reduced growth of the juveniles, and severe malformations of the appendages in the juveniles. The marbled crayfish is recommended to be considered for toxicity tests due to its easy culture in the laboratory and its genotypical uniformity.

  16. Exposure of rats to exogenous endocrine disruptors 17alpha-ethinylestradiol and benzo(a) pyrene and an estrogenic hormone estradiol induces expression of cytochromes P450 involved in their metabolism

    Czech Academy of Sciences Publication Activity Database

    Bořek-Dohalská, L.; Klusoňová, Z.; Holecová, J.; Martinková, M.; Bárta, F.; Dračínská, H.; Cajthaml, Tomáš; Stiborová, M.

    2016-01-01

    Roč. 37, Sup 1 (2016), s. 84-94 ISSN 0172-780X R&D Projects: GA ČR(CZ) GA15-02328S Institutional support: RVO:61388971 Keywords : endocrine disruptor * 17 alpha-ethinylestradiol * cytochrome P450 Subject RIV: EE - Microbiology, Virology Impact factor: 0.918, year: 2016

  17. Reference ranges of 17-hydroxyprogesterone, DHEA, DHEAS, androstenedione, total and free testosterone determined by TurboFlow-LC-MS/MS and associations to health markers in 304 men

    DEFF Research Database (Denmark)

    Jensen, L.S.; Johannsen, T H; Holmboe, Stine Agergaard

    2016-01-01

    We report reference ranges based on LC-MS/MS for testosterone (T), free testosterone (FT) and its precursors, i.e. 17-hydroxyprogesterone (17-OHP), dehydroepiandrosterone (DHEA), DHEA-sulfate (DHEAS) and androstenedione (Adione), in relation to different health markers and lifestyle factors...... of health markers in healthy men provides age-related reference ranges, and furthermore evaluates the impact of lifestyle factors and metabolic syndrome on androgen metabolite levels....

  18. The stereoisomers of 17alpha-[123I]iodovinyloestradiol and its 11beta-methoxy derivative evaluated for their oestrogen receptor binding in human MCF-7 cells and rat uterus, and their distribution in immature rats.

    Science.gov (United States)

    Rijks, L J; Boer, G J; Endert, E; de Bruin, K; van den Bos, J C; van Doremalen, P A; Schoonen, W G; Janssen, A G; van Royen, E A

    1996-03-01

    We studied the potential of both stereoisomers of 17alpha-[123I]iodovinyloestradiol (E- and Z-[123I]IVE) and of 11beta-methoxy-17alpha-[123I]iodovinyloestradiol (E- and Z-[123I]MIVE) as suitable radioligands for the imaging of oestrogen receptor(ER)-positive human breast tumours. The 17alpha-[123I]iodovinyloestradiols were prepared stereospecifically by oxidative radio-iododestannylation of the corresponding 17alpha-tri-n-butylstannylvinyloestradiol precursors. Competitive binding studies were performed in order to determine the relative binding affinity (RBA) of the unlabelled 17alpha-iodovinyloestradiols for the ER in both human MCF-7 breast tumour cells and rat uterine tissue, compared with that of diethylstilboestrol (DES). Target tissue uptake, retention and uptake selectivity of their 123I-labelled analogues were studied in immature female rats. All four 17alpha-iodovinyloestradiols showed high affinity for the ER in human MCF-7 cells, as well as rat uterus. Their RBA for the ER showed the following order of decreasing potency: RBA of DES >Z-IVE >Z-MIVE >E-MIVE > or =E-IVE. Neither of these 17alpha-iodovinyloestradiols showed any significant binding to the sex hormone binding globulin in human plasma. The biodistribution studies showed ER-mediated uptake in the uterus, ovaries and pituitary, that of E- and Z-[123I]MIVE being higher than that of E- and Z-[123I]IVE. High target-to-non-target tissue uptake ratios, especially at longer periods after injection (up to 24h), were exhibited by both isomers of [123I]MIVE. The uterus-to-blood uptake ratio was higher for E-[123I]MIVE. However, the uterus-to-fat uptake ratio appeared to be higher for the Z-isomer of [123I]MIVE, especially at 24h after injection. Metabolic properties and temperature effects, which play a more important role in vivo, probably cause the discrepancies seen between in vitro and in vivo binding results. On the basis of their in vitro binding properties and in vivo distribution characteristics

  19. Effects of exposure to 17{alpha}-ethynylestradiol during larval development on growth, sexual differentiation, and abundances of transcripts in the liver of the wood frog (Lithobates sylvaticus)

    Energy Technology Data Exchange (ETDEWEB)

    Tompsett, Amber R., E-mail: amber.tompsett@usask.ca [Toxicology Centre, University of Saskatchewan, Saskatoon, SK (Canada); Wiseman, Steve; Higley, Eric [Toxicology Centre, University of Saskatchewan, Saskatoon, SK (Canada); Giesy, John P. [Toxicology Centre, University of Saskatchewan, Saskatoon, SK (Canada); Dept. of Veterinary Biomedical Sciences, University of Saskatchewan, Saskatoon, SK (Canada); Dept. of Biology and Chemistry and State Key Laboratory for Marine Pollution, City University of Hong Kong, Hong Kong, Special Administrative Region (Hong Kong); Hecker, Markus [Toxicology Centre, University of Saskatchewan, Saskatoon, SK (Canada); School of the Environment and Sustainability, University of Saskatchewan, Saskatoon, SK (Canada)

    2013-01-15

    Populations of amphibians are in decline in certain locations around the world, and the possible contribution of environmental contaminants, including estrogenic compounds, to these declines is of potential concern. In the current study, responses of the wood frog (Lithobates sylvaticus) to exposure to 17{alpha}-ethynylestradiol (EE2), the synthetic estrogen used in oral contraceptives, during the larval period were characterized. Exposure of L. sylvaticus to 1.08, 9.55, or 80.9 {mu}g EE2/L had no effects on survival, growth, or metamorphic endpoints monitored in the current study. However, there were significant effects of exposure to EE2 on phenotypic sex ratios. In general, lesser proportions of L. sylvaticus developed as phenotypic males and greater proportions developed as phenotypic females or with mixed sex phenotypes at all concentrations of EE2 tested. Utilizing the data collected in the current study, the EC{sub 50} for complete feminization of L. sylvaticus was determined to be 7.7 {mu}g EE2/L, and the EC{sub 50} for partial feminization was determined to be 2.3 {mu}g EE2/L. In addition, after chronic exposure, abundances of transcripts of vitellogenin A2, high density lipoprotein binding protein, and 7-dehydrocholesterol reductase were 1.8-280-fold greater in livers from L. sylvaticus exposed to EE2 compared to controls. Overall, there were significant effects of exposure to all concentrations of EE2 tested, the least of which was within about 2-fold of estrogen equivalent concentrations previously measured in the environment.

  20. Sensor and instrumentation for progesterone detection

    KAUST Repository

    Zia, Asif I.

    2012-05-01

    The reported research work uses a real time and noninvasive method to detect progesterone hormone concentration in purified water using Electrochemical Impedance Spectroscopy (E.I.S.) technique. Planar capacitive sensor, consisting of inter-digitated microelectrodes, is designed and fabricated on silicon substrate using thin-film Microelectromechanical system (MEMS) based semiconductor device fabrication technology. The sensor in conjunction with EIS is used to evaluate conductivity, permeability and dielectric properties of reproductive hormone progesterone and its concentration quantification in purified water. Impedance spectrums are obtained with various concentrations of the hormone in purified water by using an electric circuit in order to extract sample conductance. Relationship of sample conductance with progesterone concentration level is studied in this research work. The ability of E.I.S. to detect progesterone concentration is aimed to be used in dairy farming industry in order to obtain better reproductive performance of the dairy cattle. © 2012 IEEE.

  1. Uses of progesterone in clinical practice.

    Science.gov (United States)

    Warren, M P; Shantha, S

    1999-01-01

    Progesterone is the natural progestagen produced by the corpus luteum during the luteal phase. It is absorbed when administered orally, but is greater than 90% metabolized during the first hepatic pass. This greatly limits the efficacy of once-daily administration and also results in unphysiologically high levels of progesterone metabolites, particularly those reduced at the 5-a position. These metabolites can cause dizziness and drowsiness to the point of preventing the operation of a motor vehicle. Synthetic progestins, such as medroxyprogesterone acetate and norethindrone acetate (NETA), have been specifically designed to resist enzymatic degradation and remain active after oral administration. However, these compounds exert undesirable effects on the liver and often cause severe psychological side effects. The permeability of the skin does not allow for administration of progesterone in the quantities normally produced by the corpus luteum, i.e., up to 25 mg/day during the mid-luteal phase. To avoid this problem, synthetic progestins such as NETA have been administered transdermally. These compounds, though, just like synthetic estrogens administered non-orally, retain undesirable hepatic effects even when administered transdermally. Transvaginal administration of progesterone is a practical non-oral route available for administering progesterone. Early experience was gained with vaginal suppositories, which lack manufacturing controls. Recently, a new progesterone gel formulation has been designed for vaginal use. The clinical acceptability of this product has been enhanced by the bioadhesive characteristics of its polycarbophil-based gel, which conveys controlled and sustained-released properties. Investigations have shown that because of local direct vagina-to-uterus transport, which results in a preferential uterine uptake of progesterone, this formulation given in conjunction with physiological amounts of estradiol produces endometrial changes similar to

  2. PROGESTERONE EXERTS NEUROPROTECTIVE EFFECTS AFTER BRAIN INJURY

    OpenAIRE

    Stein, Donald G.

    2007-01-01

    Progesterone, although still widely considered primarily a sex hormone, is an important agent affecting many central nervous system functions. This review assesses recent, primarily in vivo, evidence that progesterone can play an important role in promoting and enhancing repair after traumatic brain injury and stroke. Although many of its specific actions on neuroplasticity remain to be discovered, there is growing evidence that this hormone may be a safe and effective treatment for traumatic...

  3. Progesterone exerts neuroprotective effects after brain injury.

    Science.gov (United States)

    Stein, Donald G

    2008-03-01

    Progesterone, although still widely considered primarily a sex hormone, is an important agent affecting many central nervous system functions. This review assesses recent, primarily in vivo, evidence that progesterone can play an important role in promoting and enhancing repair after traumatic brain injury and stroke. Although many of its specific actions on neuroplasticity remain to be discovered, there is growing evidence that this hormone may be a safe and effective treatment for traumatic brain injury and other neural disorders in humans.

  4. Synthesis and biological properties of 7alpha-cyano derivatives of the (17alpha,20E/Z)-[125I]iodovinyl- and 16alpha-[125I]iodo-estradiols.

    Science.gov (United States)

    Ali, Hasrat; Rousseau, Jacques; Paquette, Benoit; Dubé, Charlotte; Marko, Bernadette; van Lier, Johan E

    2003-12-01

    The synthesis, receptor binding affinity, estrogenic potency and tissue distribution of the 7alpha-cyano derivatives of the (17alpha,20E/Z)-[125I]iodovinyl-(CIVE) and 16alpha-[125I]iodo-estradiols (CIE) are reported. The iodovinyl derivatives were prepared via the (17alpha,20E/Z)-tri-n-butylstannyl intermediates, derived from the addition of tri-n-butyl tin hydride to the 17alpha-ethynyl group of the 7alpha-cyano-17alpha-ethynylestradiol, using triethylborane as a catalyst. The no-carrier-added [125I]-CIVE isomers were prepared via the same stereospecific reaction. [125I]-CIE was prepared from 7alpha-cyano-16beta-bromoestradiol via halogen exchange with Na125I. Addition of the 7alpha-cyano group to 16alpha-iodoestradiol did not affect estrogen receptor binding affinity (RBA of CIE is 115). However the estrogenic potential of CIE, as measured by the capacity to stimulate the expression of the pS2 gene, was reduced to 1% as compared to that of estradiol. Addition of a 7alpha-cyano group to the (17alpha,20E/Z)-IVE isomers reduced the RBA to 21 and 36, respectively, while the estrogenic potential was reduced to 2-3% of that of estradiol. Uterus uptake in immature rats of the 125I-labeled CIVE 20E-isomer and the 16alpha-iodo CIE peaked at 0.5h post injection while the (17alpha,20Z)-CIVE isomer showed a maximum only past 5h post injection. Uptake of all three 125I-labeled 7alpha-cyanoestrogens was suppressed by the co-injection of non-radioactive estradiol confirming the role of estrogen receptors in the localization process. Uterus retention pattern differ substantially from those of the analogues 7alpha-methylestrogens, which were previously shown to give high maximum 125I-uptake values at 2h post injection. Overall our data indicate that addition of a 7alpha-cyano group to 123I-labeled estrogens does not improve their potential to serve as SPECT agents for the imaging of estrogen receptor densities in breast cancer.

  5. Functional glucocorticoid receptor gene variants do not underlie the high variability of 17-hydroxyprogesterone screening values in healthy newborns.

    Science.gov (United States)

    Schreiner, Felix; Tozakidou, Magdalini; Maslak, Rita; Holtkamp, Ute; Peter, Michael; Gohlke, Bettina; Woelfle, Joachim

    2009-04-01

    17-Hydroxyprogesterone (17-OHP) screening for classical congenital adrenal hyperplasia (CAH) is part of many newborn screening programs worldwide. Cut-off values are relatively high, and screening sensitivity does not reach 100%. Recently, the glucocorticoid receptor (GR) N363S-variant has been linked to relatively low degree of virilization and comparatively lower 17-OHP serum concentrations in clinically diagnosed female CAH patients. We sought to determine whether functional GR gene variants, either increasing (N363S, BclI) or decreasing GR sensitivity (R23K), underlie the variable 17-OHP screening levels in healthy newborns. GR genotypes were compared with 17-OHP screening values in 1000 random samples from routine screening. 17-OHP was measured by conventional immunoassay (TRFIA) and a liquid chromatography-tandem mass spectrometry method (LC-MS/MS), which has been shown to increase screening specificity by steroid profiling and avoiding cross-reactions of the 17-OHP-antibody. There was no significant association of 17-OHP with GR genotypes, even after inclusion of gestational and postnatal age as covariates. However, among LC-MS/MS steroid measurements, we observed some unexpected trends, including lower 11-deoxycortisol concentrations in both 363S- and 23K-carriers. For carriers of the frequent BclI variant, linear regression analysis revealed a significant increase of 4-androstenedione levels with every mutant allele inherited. Functional GR variants do not underlie the variation of 17-OHP values observed in healthy individuals. However, whether and to which extent genetically determined differences in individual GR sensitivity influence 17-OHP screening levels in conditions of a pathological hypothalamus-pituitary-adrenal gland-axis stimulation and thus may explain false-negative screening results in those affected by CAH remains to be investigated.

  6. Progesterone induces adult mammary stem cell expansion.

    Science.gov (United States)

    Joshi, Purna A; Jackson, Hartland W; Beristain, Alexander G; Di Grappa, Marco A; Mote, Patricia A; Clarke, Christine L; Stingl, John; Waterhouse, Paul D; Khokha, Rama

    2010-06-10

    Reproductive history is the strongest risk factor for breast cancer after age, genetics and breast density. Increased breast cancer risk is entwined with a greater number of ovarian hormone-dependent reproductive cycles, yet the basis for this predisposition is unknown. Mammary stem cells (MaSCs) are located within a specialized niche in the basal epithelial compartment that is under local and systemic regulation. The emerging role of MaSCs in cancer initiation warrants the study of ovarian hormones in MaSC homeostasis. Here we show that the MaSC pool increases 14-fold during maximal progesterone levels at the luteal dioestrus phase of the mouse. Stem-cell-enriched CD49fhi cells amplify at dioestrus, or with exogenous progesterone, demonstrating a key role for progesterone in propelling this expansion. In aged mice, CD49fhi cells display stasis upon cessation of the reproductive cycle. Progesterone drives a series of events where luminal cells probably provide Wnt4 and RANKL signals to basal cells which in turn respond by upregulating their cognate receptors, transcriptional targets and cell cycle markers. Our findings uncover a dynamic role for progesterone in activating adult MaSCs within the mammary stem cell niche during the reproductive cycle, where MaSCs are putative targets for cell transformation events leading to breast cancer.

  7. Dgroup: DG00467 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available DG00467 Chemical ... DGroup Hydroxyprogesterone ... D08052 ... Hydroxyprogesterone (INN) D00949 ... Hydroxyprogest...erone caproate (JAN/USP/INN) ... D08053 ... Hydroxyprogesterone 17alfa-acetate Other ... DG01666 ... Progest...erone receptor agonist ... DG02004 ... Progesterone ATC code: G03DA03 Progestin NR3C3 (PGR) [HSA:5241] [KO:K08556] ...

  8. Effect of exogenous progesterone on oestrus response of West ...

    African Journals Online (AJOL)

    Twenty-four (24) healthy, parous West African dwarf (WAD) does aged 2 – 3 years were used to study the effects of varying doses of progesterone on oestrus synchronization and plasma progesterone levels. The does were randomly assigned to 4 treatment groups consisting of 12.5, 25.0 and 37.5 mg progesterone ...

  9. Progesterone receptor expression declines in the guinea pig uterus during functional progesterone withdrawal and in response to prostaglandins.

    Directory of Open Access Journals (Sweden)

    Toni N Welsh

    Full Text Available Progesterone withdrawal is essential for parturition, but the mechanism of this pivotal hormonal change is unclear in women and other mammals that give birth without a pre-labor drop in maternal progesterone levels. One possibility suggested by uterine tissue analyses and cell culture models is that progesterone receptor levels change at term decreasing the progesterone responsiveness of the myometrium, which causes progesterone withdrawal at the functional level and results in estrogen dominance enhancing uterine contractility. In this investigation we have explored whether receptor mediated functional progesterone withdrawal occurs during late pregnancy and labor in vivo. We have also determined whether prostaglandins that induce labor cause functional progesterone withdrawal by altering myometrial progesterone receptor expression. Pregnant guinea pigs were used, since this animal loses progesterone responsiveness at term and gives birth in the presence of high maternal progesterone level similarly to primates. We found that progesterone receptor mRNA and protein A and B expression decreased in the guinea pig uterus during the last third of gestation and in labor. Prostaglandin administration reduced while prostaglandin synthesis inhibitor treatment increased progesterone receptor A protein abundance. Estrogen receptor-1 protein levels remained unchanged during late gestation, in labor and after prostaglandin or prostaglandin synthesis inhibitor administration. Steroid receptor levels were higher in the non-pregnant than in the pregnant uterine horns. We conclude that the decreasing expression of both progesterone receptors A and B is a physiological mechanism of functional progesterone withdrawal in the guinea pig during late pregnancy and in labor. Further, prostaglandins administered exogenously or produced endogenously stimulate labor in part by suppressing uterine progesterone receptor A expression, which may cause functional progesterone

  10. Progesterone Receptor Expression Declines in the Guinea Pig Uterus during Functional Progesterone Withdrawal and in Response to Prostaglandins

    Science.gov (United States)

    Welsh, Toni N.; Hirst, Jonathan J.; Palliser, Hannah; Zakar, Tamas

    2014-01-01

    Progesterone withdrawal is essential for parturition, but the mechanism of this pivotal hormonal change is unclear in women and other mammals that give birth without a pre-labor drop in maternal progesterone levels. One possibility suggested by uterine tissue analyses and cell culture models is that progesterone receptor levels change at term decreasing the progesterone responsiveness of the myometrium, which causes progesterone withdrawal at the functional level and results in estrogen dominance enhancing uterine contractility. In this investigation we have explored whether receptor mediated functional progesterone withdrawal occurs during late pregnancy and labor in vivo. We have also determined whether prostaglandins that induce labor cause functional progesterone withdrawal by altering myometrial progesterone receptor expression. Pregnant guinea pigs were used, since this animal loses progesterone responsiveness at term and gives birth in the presence of high maternal progesterone level similarly to primates. We found that progesterone receptor mRNA and protein A and B expression decreased in the guinea pig uterus during the last third of gestation and in labor. Prostaglandin administration reduced while prostaglandin synthesis inhibitor treatment increased progesterone receptor A protein abundance. Estrogen receptor-1 protein levels remained unchanged during late gestation, in labor and after prostaglandin or prostaglandin synthesis inhibitor administration. Steroid receptor levels were higher in the non-pregnant than in the pregnant uterine horns. We conclude that the decreasing expression of both progesterone receptors A and B is a physiological mechanism of functional progesterone withdrawal in the guinea pig during late pregnancy and in labor. Further, prostaglandins administered exogenously or produced endogenously stimulate labor in part by suppressing uterine progesterone receptor A expression, which may cause functional progesterone withdrawal, promote

  11. Progesterone Receptor Scaffolding Function in Breast Cancer

    Science.gov (United States)

    2012-10-01

    response. PR are expressed in multiple human tissues including the uterus, mammary gland , brain, pancreas, thymus , bone, ovary, testes, and in the...ABSTRACT Progesterone receptors (PR) are critical mediators of mammary gland development and contribute to breast cancer progression. Progestin...receptors (PR) are critical for massive breast epithelial cell expansion during mammary gland development and contribute to breast cancer progression

  12. Determination of plasma progesterone during pregnancy

    NARCIS (Netherlands)

    Molen, H.J. van der

    A modification of Short's method for the determination of plasma progesterone is described, which allows the estimation of 0.5–1.0 μg per sample. The reliability of the method is tested and plasma levels in cord and peripheral blood during pregnancy are reported.

  13. Estrogen receptor, progesterone receptor, and human epidermal ...

    African Journals Online (AJOL)

    Current clinical practice employs the use of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2), as biomarkers to appropriately select patients that would benefit from targeted therapy against these major molecular pathways of the disease. This study aims at ...

  14. Milk progesterone concentrations: an accurate early pregnancy ...

    African Journals Online (AJOL)

    The optimal day of milk sampling for pregnancy diagnosis by milk progesterone quantitation was determined as well as the diagnostic efficiency of the test for days 14- 24 post insemination in dairy cattle. The results show that on days. 22 and 23 after insemination diagnostic efficiencies of approximately 100% can be ...

  15. Comparing intramuscular progesterone, vaginal progesterone and 17 -hydroxyprogestrone caproate in IVF and ICSI cycle

    Directory of Open Access Journals (Sweden)

    Ashraf Moini

    2011-01-01

    Full Text Available Background: Supplementation of luteal phase with progesterone is prescribed for women undergoing routine IVF treatment.Objective: The objective of this study was to compare the efficacy of three types of progesterone on biochemical, clinical and ongoing pregnancy rates and abortion and live birth rates.Materials and Methods: A prospective randomized study was performed at Royan Institute between March 2008 and March 2009 in women under 40 years old, who use GnRH analog down-regulation. One hundred eighty six patients in three groups were received progesterone in oil (100 mg, IM daily, intravaginal progesterone (400 mg, twice daily and 17- hydroxyprogestrone caproate (375mg, every three days, respectively.Results: Final statistical analysis after withdrawal of some patients was performed in 50, 50 and 53 patients in group 1, 2 and 3 respectively. No differences between the groups were found in baseline characteristics. No statistical significance different was discovered for biochemical, clinical and ongoing pregnancies. Although the abortion rate was statistically higher in group 1 (p=0.025 the live birth rate was not statistically significant between the three groups.Conclusion: The effects of three types of progesterone were similar on pregnancies rate. We suggest the use of intravaginal progesterone during the luteal phase in patients undergoing an IVF-ET program because of the low numbers of abortions, and high ongoing pregnancy rates

  16. Removal of estrone, 17alpha-ethinylestradiol, and 17beta-estradiol in algae and duckweed-based wastewater treatment systems.

    Science.gov (United States)

    Shi, Wenxin; Wang, Lizheng; Rousseau, Diederik P L; Lens, Piet N L

    2010-05-01

    Many pollutants have received significant attention due to their potential estrogenic effect and are classified as endocrine disrupting compounds (EDCs). Because of possible ecological effects and increased attention for water reuse schemes, it is important to increase our understanding of the EDC removal capacities of various wastewater treatment systems. However, there has so far been little research on the fate and behavior of EDCs in stabilization pond systems for wastewater treatment, which represent an important class of wastewater treatment systems in developing countries because of their cost-effectiveness. The aim of this work is to study the fate and behavior of EDCs in algae and duckweed ponds. Because the synthetic hormone 17alpha-ethinylestradiol (EE2) and the natural hormones estrone (E1), as well as 17beta-estradiol (E2), have been detected in effluents of sewage treatment plants and been suggested as the major compounds responsible for endocrine disruption in domestic sewage; E1, E2, and EE2 were therefore chosen as target chemicals in this current work. Both batch tests and continuous-flow tests were carried out to investigate the sorption and biodegradation of estrogens in algae and duckweed pond systems. The applied duckweed was a Lemna species. The applied algae was a mixture of pure cultures of six different algae genera, i.e., Anabaena cylindrica, Chlorococcus, Spirulina platensis, Chlorella, Scenedesmus quadricauda, and Anaebena var. Synthetic wastewater were used in all tests. The concentrations of estrogens were measured with three different enzyme-linked immunosorbent assay kits specific for E1, E2, or EE2. When the concentrations of estrogens in water samples were below the lowest quantitative analysis range (0.05 microg/l), preconcentration of the water samples were performed by means of solid phase extraction (SPE) with C18 cartridges. The 6-day batch tests show that the presence of algae or duckweed accelerated the removal of the three

  17. 17-Hydroxyprogesterone Test

    Science.gov (United States)

    ... High-sensitivity C-reactive Protein (hs-CRP) Histamine Histone Antibody HIV Antibody and HIV Antigen (p24) HIV ... activity of the enzyme for which the gene codes. Parents may be carriers , and carriers may not ...

  18. 17-Hydroxyprogesterone Test

    Science.gov (United States)

    ... a female has increased growth of facial and body hair ( hirsutism ) or other symptoms that could be related ... who have symptoms such as excess facial and body hair and irregular periods. This includes women with suspected ...

  19. Endocrine-disrupting activities in vivo of the fungicides tebuconazole and epoxiconazole

    DEFF Research Database (Denmark)

    Taxvig, Camilla; Hass, Ulla; Petersen, Marta Axelstad

    2007-01-01

    synthesis pathway in the Leydig cells. The high dose of epoxiconazole had marked fetotoxic effects, while the lower dose caused increased birth weights. The increased birth weights may be explained by a marked increase in testosterone levels in dams during gestation. Common features for azole fungicides...... on male offspring as shown by increased nipple retention. This effect was likely caused by the reduced testosterone levels seen in male fetuses. Tebuconazole increased the testicular concentrations of progesterone and 17 alpha-hydroxyprogesterone in male fetuses, indicating a direct impact on the steroid...

  20. The influence of seasonality and manufacturer kit lot changes on 17α-hydroxyprogesterone measurements and referral rates of congenital adrenal hyperplasia in newborns.

    Science.gov (United States)

    Pearce, Melissa; Dauerer, Erin; DiRienzo, A Gregory; Caggana, Michele; Tavakoli, Norma P

    2017-01-01

    Newborn screening for congenital adrenal hyperplasia (CAH) is performed by measuring the concentration of 17α-hydroxyprogesterone (17-OHP) in dried blood spots. Unfortunately, the level of 17-OHP varies due to multiple factors, and therefore, the false positive rate for the test is a challenge. We analyzed screening data from 2007 to 2015 to determine the effect of seasonal changes and manufacturer kit lot changes on 17-OHP values and on numbers of infants referred. Data from screening 2.2 million infants over a 9-year period indicates that in the NYS during the colder months, daily mean 17-OHP values are higher, more retests are performed, and more infants are referred even though fewer infants are born. The practice of using fixed cutoffs for referring infants for CAH leads to more false positive results in colder months. In addition, there was an overall 10% increase in the daily mean 17-OHP values from the 2 years before and after a manufacturer kit lot change that occurred in November 2013, suggestive of a functional change in the kit at that time. Newborn screening programs should be cognizant of seasonal temperature variations and (un)anticipated manufacturer kit changes because they may affect 17-OHP values and CAH referral rates. What is Known: • Newborn screening for congenital adrenal hyperplasia is generally performed by measuring 17α-hydroxyprogesterone (17-OHP) levels in dried blood spots. • 17-OHP concentrations are affected by gestational age/weight of infant when specimen is collected, specimen collection time after birth, as well as race and sex of infant. What is New: • Seasonal temperature variations and unanticipated manufacturer kit changes affect 17-OHP levels and consequently referral rates in programs that use fixed cutoffs. • Daily mean 17-OHP is generally higher when the ambient temperature is lower.

  1. Childhood conditions influence adult progesterone levels.

    Directory of Open Access Journals (Sweden)

    Alejandra Núñez-de la Mora

    2007-05-01

    Full Text Available Average profiles of salivary progesterone in women vary significantly at the inter- and intrapopulation level as a function of age and acute energetic conditions related to energy intake, energy expenditure, or a combination of both. In addition to acute stressors, baseline progesterone levels differ among populations. The causes of such chronic differences are not well understood, but it has been hypothesised that they may result from varying tempos of growth and maturation and, by implication, from diverse environmental conditions encountered during childhood and adolescence.To test this hypothesis, we conducted a migrant study among first- and second-generation Bangladeshi women aged 19-39 who migrated to London, UK at different points in the life-course, women still resident in Bangladesh, and women of European descent living in neighbourhoods similar to those of the migrants in London (total n = 227. Data collected included saliva samples for radioimmunoassay of progesterone, anthropometrics, and information from questionnaires on diet, lifestyle, and health. Results from multiple linear regression, controlled for anthropometric and reproductive variables, show that women who spend their childhood in conditions of low energy expenditure, stable energy intake, good sanitation, low immune challenges, and good health care in the UK have up to 103% higher levels of salivary progesterone and an earlier maturation than women who develop in less optimal conditions in Sylhet, Bangladesh (F9,178 = 5.05, p < 0.001, standard error of the mean = 0.32; adjusted R(2 = 0.16. Our results point to the period prior to puberty as a sensitive phase when changes in environmental conditions positively impact developmental tempos such as menarcheal age (F2,81 = 3.21, p = 0.03 and patterns of ovarian function as measured using salivary progesterone (F2,81 = 3.14, p = 0.04.This research demonstrates that human females use an extended period of the life cycle prior

  2. [Reproductive physiology of the European mink: progesterone profile during pregnancy].

    Science.gov (United States)

    Amstislavskiĭ, S Ia; Zav'ialov, E L; Ternovskaia, Iu G; Gerlinskaia, L A

    2010-04-01

    Reproductive physiology of the European mink, an endangered mustelid species, has been so far scarcely investigated. This study confirms that in European mink embryo implantation occurs on the day 12 of pregnancy. Progesterone profile during pregnancy has been compared in European mink and domestic ferret. In both species, progesterone increases at peri-implantation period, i. e. on day 8 and day 12 after mating. However, toward the end of pregnancy, on day 40 after mating, progesterone concentration in faeces of the ferrets decreases and does not differ from the initial level. In contrast, increase of progesterone during first 12 days of pregnancy in European mink is not as rapid as in ferrets, but in this species, there is no visible decrease of progesterone at the end of pregnancy. Peak levels of progesterone in faeces (day 8, 12) are lower in European mink than in ferret.

  3. Autoimmune Progesterone Dermatitis Presenting as Stevens-Johnson Syndrome.

    Science.gov (United States)

    Drayer, Sara M; Laufer, Larry R; Farrell, Maureen E

    2017-10-01

    Autoimmune progesterone dermatitis is an uncommon disease presenting with cyclical skin eruptions corresponding with the menstrual cycle luteal phase. Because symptoms are precipitated by rising progesterone levels, treatment relies on hormone suppression. A 22-year-old nulligravid woman presented with symptoms mistaken for Stevens-Johnson syndrome. A cyclic recurrence of her symptoms was noted, and the diagnosis of autoimmune progesterone dermatitis was made by an intradermal progesterone challenge. After 48 months, she remained refractory to medical management and definitive surgical treatment with bilateral oophorectomy was performed. Autoimmune progesterone dermatitis is a challenging diagnosis owing to its rarity and variety of clinical presentations. Treatment centers on suppression of endogenous progesterone and avoidance of exogenous triggers. When these modalities fail, surgical management must be undertaken.

  4. The benefits of progesterone therapy in imminent abortion

    Directory of Open Access Journals (Sweden)

    A. Abadi

    2005-12-01

    Full Text Available The causes of imminent abortion are multi-factorial. The biggest causal factor is the low level of serum progesterone level. The lowest critical level of serum progesterone for survivability of pregnancy is 10 ng/ml. Eighty percent of patients experiencing abortion showed that their progesterone level was < 10 ng/ml. Patients who realized that their pregnancy would experience hemorrhage generally would suffer from depression. Stress was one of the factors responsible for the occurence of abortion. Administration of natural progesterone substitution (not  progestogen accelerates the disappearance of uterine contractions, and speeds up the stoppage of bleeding. In addition, progesterone has the effect of anti-anxiety. Adminstration of oral progesterone would result in metabolism in the intestine and liver, such that physiological level of serum progesterone could not be reached, while administration of suppositoria progesterone would result in physiological level of serum, such that it was effective to prevent imminent abortion. (Med J Indones 2005; 14:258-62Keywords: progesterone, imminent abortion

  5. Induction of LH hypersecretion in cyclic rats during the afternoon of oestrus by oestrogen in conjunction with progesterone antagonism or opioidergic blockade.

    Science.gov (United States)

    Lustig, R H; Pfaff, D W; Fishman, J

    1988-05-01

    The pro-oestrous secretion of progesterone that follows the LH surge in the rat limits the expression of the daily signal for LH surge initiation until the following oestrous cycle. This study explored the role of endogenous opioid peptides in the extinction by progesterone of the signal for the LH surge induced by oestrogen. Intact cyclic rats underwent external jugular venous cannulation on dioestrus, and were allowed to elicit a spontaneous pro-oestrous LH surge. On the afternoon of pro-oestrus, rats received an s.c. injection of oestradiol and an s.c. injection of either oil, 17 beta-hydroxy-11 beta-(4-dimethylaminophenyl)17 alpha-(prop-1-ynyl)oestra-4,9,dien-3-one (RU 486; a synthetic anti-progestin), or N-cyclopropylmethyl-6-desoxy-6-methylene-noroxy-morphone (nalmefene; a long-acting opiate antagonist). Repeat doses of each were administered on the morning of oestrus to maintain increased oestrogen levels, and either progesterone or opioidergic blockade. Plasma was obtained from 13.00 to 19.00 h on oestrus for determination of the concentration of rat LH. Rats treated with oestradiol alone demonstrated consistently low concentrations of LH throughout the afternoon of oestrus. Rats treated with both oestradiol and either RU 486 or nalmefene demonstrated spontaneous augmentations of rat LH concentration during the afternoon of oestrus, which, although of diminished amplitude as compared with that seen in pro-oestrus, were consistent with a reactivation of the LH surge-generating mechanism. Rats treated with nalmefene in the absence of oestradiol were unable to augment LH secretion spontaneously.(ABSTRACT TRUNCATED AT 250 WORDS)

  6. [Effects of electroacupuncture of "Guanyuan" (CV 4)-"Zhongji" (CV 3) on ovarian P450 arom and P450c 17alpha expression and relevant sex hormone levels in rats with polycystic ovary syndrome].

    Science.gov (United States)

    Sun, Jie; Zhao, Ji-meng; Ji, Rong; Liu, Hui-rong; Shi, Yin; Jin, Chun-lan

    2013-12-01

    To observe the effect of electroacupuncture (EA) on ovarian P 450 arom and P 450 c 17 alpha (aromatases) expression and related sex hormone levels in polycystic ovary syndrome (PCOS) rats. Thirty SD rats were randomly divided into normal control group, model group and EA group (10 rats/group). PCOS model was made by intragastric administration of letrozole at 1 mg/kg per day for consecutive 21 days. "Guanyuan" (CV 4) and "Zhongji" (CV 3) acupoints were stimulated 20 min by EA (2 mA, 2 Hz), once daily for consecutive 14 days. The damp ovarian weight was weighed and the pathological changes of the ovarian tissue were observed after H. E. staining. Ultrastructural changes of the ovarian tissue were observed by transmission electron microscope. Immunohistochemical staining was adopted to detect ovarian follicle granulosa cell P 450 arom and follicle membrane cell P 450 c 17 alpha expression. The contents of estradiol (E 2), estrone (E 1), androstenedione (ASD), testosterone (T), follicle-stimulating hormone (FSH) and luteinizing hormone (LH) in the ovarian tissue were measured by ELISA. Compared with the normal group, there was a significant increase in the damp weight of both left and right ovarian tissues in the model group (P ovary, thinning of the granular cell layer, and disappearance of the intraovular oocytes and coronaradiata under light microscope, and mitochondrion swelling, fracture or disappearance of mitochondrial cristae, and enlargement of the endoplasmic reticulum, etc. after modeling were obviously improved in the EA group. In comparison to the control group, the expression of the follicle granulosa cell P450 arom was significantly down-regulated and that of follicle membrane cell P 450 c 17 alpha was significantly upregulated in the model group (P < 0.01). After EA intervention these changes were obviously reversed (P < 0.05, P < 0.01). In the model group, there was a significant increase in the levels of ASD, T and LH in the ovarian tissues (P < 0

  7. Progesterone supplementation in women with otherwise unexplained recurrent miscarriages

    Directory of Open Access Journals (Sweden)

    Munawar Hussain

    2012-01-01

    Full Text Available Context: Recurrent miscarriages, the loss of three or more consecutive intrauterine pregnancies before 20 weeks of gestation with the same partner, affect 1%-1.5% of the pregnant population. The inadequate secretion of progesterone in early pregnancy has been proposed as a cause of recurrent miscarriages. Aims: The aim was to investigate the efficacy of progesterone supplementation in patients with unexplained recurrent miscarriages. Settings And Design: This was a 9-year cohort study of women with otherwise unexplained recurrent miscarriages who attended a recurrent miscarriage clinic in a tertiary care university hospital. Subjects and Methods: Women with at least three unexplained recurrent miscarriages were included in the study. They were divided into three groups according to their initial and 48-h repeat progesterone levels. For women with inadequate endogenous progesterone secretion, natural progesterone vaginal pessaries 400 mg 12-hourly were offered until 12 weeks gestation. Statistical Analysis: Proportions and 95% confidence intervals calculated for categorical variables and the chi-square test were used to show statistical significance. Medians and ranges were calculated for noncontinuous variables. Results: Pregnancy cycles (n = 203 were analyzed to examine the miscarriage rate following progesterone supplementation. Overall live birth and miscarriage rates were 63% and 36%, respectively. When analyzed by the number of previous miscarriages there was a reduction in the miscarriage rate following progesterone supplementation in women with 4 previous miscarriages when compared with historical data. Conclusions: Progesterone supplementation may have beneficial effects in women with otherwise unexplained recurrent miscarriages.

  8. Perspectives for on-site monitoring of progesterone

    NARCIS (Netherlands)

    Posthuma-Trumpie, G.A.; Amerongen, van A.; Korf, J.; Berkel, van W.J.H.

    2009-01-01

    The steroid hormone progesterone is the primary biomarker of the reproductive status of female mammals. Current techniques of monitoring progesterone are based predominantly on (enzyme) immunoassays, but these are too expensive to be affordable in daily screening programmes because of their

  9. Progesterone profiles of postpartum dairy cows as an aid to ...

    African Journals Online (AJOL)

    mining the concentration of progesterone in milk samples. (Laing & Heap, 1971; Darling, Laing & Harkness, 1974). The rapid measurement of progesterone in milk using a semi-automated radioimmunoassay (RIA) is now a well established technique for pregnancy diagnosis in dairy cows. (Booth & Holdsworth, 1976).

  10. Progesterone, Estradiol and their Receptors in Leiomyomata and the

    African Journals Online (AJOL)

    Estradiol and progesterone binding in uterine leiomyomata and in normal uterine tissues. Obstetrics and. Gynaecology. 1980; 55: 4-20. 4. Jorge RP, Edgrad C, Jacques G,. Christine V, Bernard S and Albert N. Effect of Decapeptyl, an agonist analog of GnRH on estrogens, estrogen sulfates, and progesterone receptors in.

  11. Diagnosis of pregnancy in dairy cows based on the progesterone ...

    African Journals Online (AJOL)

    A linear discriminant function (LDF) was used to estimate the level of milk progesterone which allowed the best overall classification of dairy cows into pregnant and non-pregnant groups (confirmed by rectal palpation). Progesterone levels were measured in milk samples drawn between 20 and 24 days after insemination.

  12. A Randomized Trial of Progesterone in Women with Recurrent Miscarriages

    NARCIS (Netherlands)

    Coomarasamy, Arri; Williams, Helen; Truchanowicz, Ewa; Seed, Paul T; Small, Rachel; Quenby, Siobhan; Gupta, Pratima; Dawood, Feroza; Koot, Yvonne E M; Bender Atik, Ruth; Bloemenkamp, Kitty W M; Brady, Rebecca; Briley, Annette L; Cavallaro, Rebecca; Cheong, Ying C; Chu, Justin J; Eapen, Abey; Ewies, Ayman; Hoek, Annemieke; Kaaijk, Eugenie M; Koks, Carolien A M; Li, Tin-Chiu; MacLean, Marjory; Mol, Ben W; Moore, Judith; Ross, Jackie A; Sharpe, Lisa; Stewart, Jane; Vaithilingam, Nirmala; Farquharson, Roy G; Kilby, Mark D; Khalaf, Yacoub; Goddijn, Mariette; Regan, Lesley; Rai, Rajendra

    2015-01-01

    BACKGROUND: Progesterone is essential for the maintenance of pregnancy. However, whether progesterone supplementation in the first trimester of pregnancy would increase the rate of live births among women with a history of unexplained recurrent miscarriages is uncertain. METHODS: We conducted a

  13. Carbopol-based gels for nasal delivery of progesterone.

    Science.gov (United States)

    Rathnam, Grace; Narayanan, N; Ilavarasan, R

    2008-01-01

    The purpose of this study was to investigate the nasal absorption of progesterone from carbopol-based nasal gels in rabbits. Progesterone nasal gels were prepared by dispersing carbopol 974 (1%, 1.5%, and 2%) in distilled water followed by addition of progesterone/progesterone-beta cyclodextrin complex dissolved in propylene glycol then neutralization. The potential use of beta cyclodextrin (CD) as nasal absorption enhancer by simple addition, as a physical mixture and as a complex with progesterone was investigated. The absolute bioavailability of progesterone from nasal gels in rabbits was studied by estimating the serum progesterone level by competitive solid-phase enzyme immunoassay in comparison to intravenous injection. The carbopol gel formulations produced a significant increase in bioavailability. CD complex promotes the nasal absorption of progesterone from carbopol gels as compared with gels where the CD is added by simple addition and gels which do not contain CD. This method of addition of CD as an inclusion complex in the gels could be considered as a preferred platform in nasal drug administration.

  14. Effect of Progesterone Therapy versus Diet Modification on ...

    African Journals Online (AJOL)

    Effect of Progesterone Therapy versus Diet Modification on Constipation during Pregnancy. ... Aim: To compare the effect of progesterone versus diet modification in the treatment of constipation during pregnancy. Subjects and Methods: ... A randomized placebo controlled trial is required to confirm the data of this study.

  15. Women's Perspective on Progesterone: A Qualitative Study Conducted in Australia.

    Science.gov (United States)

    Spark, M Joy; Dunn, Rebecca A; Houlahan, Kelli L

    2009-01-01

    This study explored the perspective of women using compounded progesterone preparations. Semi-structured interviews were conducted in Victoria, Australia with eight self-selected women who were dispensed a progesterone-only preparation. Participating women gained symptome relief for migraine, painful breasts, mood swings, bloating, hot flushes, and other conditions. The participants also experienced unexpected benefits such as improvement in irregular and painful periods, relief from cystitis, or increased libido, without any reported negative side effects. The participants appreciated the ability to adjust the dose and dosage form to their individual requirements and held a positive perception of progesterone as a "natural" product. Accessibility of progesterone treatment is limited due to the limited number of doctors that have knowledge about the treatment, little information available for lay people, and cost. Participants who had been treated with progesterone were willing to share their experience with others, and many heard about progesterone therapy from their social contacts. The cost of progesterone therapy, which was often more expensive than traditional hormone replacement therapy, was outweighed by the benefits received. These women found that progesterone treatment, although hard to access, was beneficial over conventional therapy.

  16. Progesterone, selected heavy metals and micronutrients in pregnant ...

    African Journals Online (AJOL)

    Background: Environmental and endocrine factors have been implicated in the aetiology of recurrent abortion, with poorly understood roles. Luteal phase insufficiency marked with insufficient progesterone secretion has been reported. Objective: To define the involvement of progesterone, trace metals, and Vitamin E in ...

  17. Diagnosis of pregnancy in dairy cows based on the progesterone ...

    African Journals Online (AJOL)

    Two of the many factors which may affect the accuracy of pregnancy diagnosis using milk progesterone levels are day of sampling and number of samples taken per cow. These two aspects were analysed using information obtained from progesterone profiles encompassing 359 pregnancy tests. Where a single sample was ...

  18. Progesterone withdrawal I: pro-convulsant effects.

    Science.gov (United States)

    Moran, M H; Smith, S S

    1998-10-05

    Pro-convulsant withdrawal properties have been reported for a variety of GABA-modulatory drugs, such as the benzodiazepines (BDZs, [S.E. File, The history of BDZ dependence: a review of animal studies, Neurosci. Biobehav. Rev. 14 (1990) 135-146; P.R. Finley, P. E. Nolan, Precipitation of BDZ withdrawal following sudden discontinuation of midazolam, DICP 23 (1989) 151-152]), barbiturates and ethanol [N. Kokka, D.E. Sapp, U. Witte, R.W. Olsen, Sex differences in sensitivity to pentylenetetrazol but not in GABAA receptor binding, Pharm. Biochem. Behav. 43 (1992) 441-447]. In this report, we test the hypothesis that pro-convulsant effects are produced by withdrawal from the GABA-modulatory neurosteroid 3alpha-OH-5alpha-pregnan-20-one (3alpha,5alpha-THP) after sustained exposure to elevated circulating levels of its parent compound progesterone (P). Seizure activity was precipitated by picrotoxin or with the BDZ inverse agonist n-methyl-beta-carboline-3-carboxamide (beta-CC), and a seizure rating determined 24 h after abrupt discontinuation of P following a multiple withdrawal/chronic administration paradigm. In some cases, a pseudopregnant rat model was employed to produce increased ovarian production of P prior to withdrawal (ovariectomy). Rats undergoing P withdrawal exhibited greater seizure-like activity than vehicle-treated controls, and received seizure scores in the same range as rats undergoing BDZ withdrawal. Administration of a 5alpha-reductase blocker, MK-906, along with P, prevented this pro-convulsant effect of P withdrawal, suggesting that the GABA-modulatory 3alpha,5alpha-THP is the active compound responsible for this withdrawal effect. Combined administration of P and diazepam produced synergistic effects upon withdrawal and produced a seizure score higher than observed after withdrawal from either agent alone. These results suggest that P exhibits withdrawal properties via the neuroactive steroid 3alpha, 5alpha-THP, that include exacerbation of

  19. Progesterone Negatively Regulates BCRP in Progesterone Receptor-Positive Human Breast Cancer Cells

    Directory of Open Access Journals (Sweden)

    Xiaojuan Wu

    2013-08-01

    Full Text Available Background/Aims: Breast cancer resistance protein (BCRP plays a crucial role in multidrug resistance (MDR. Previous studies have shown that steroid hormones, like progesterone (PROG, regulate BCRP expression. The presence of a progesterone response element (PRE in the BCRP promoter, suggests that PROG may regulate transcription of BCRP. Methods: To investigate the role of PROG in the regulation of BCRP expression, two constructs encoding full-length BCRP driven by either an endogenous PRE promoter or a constitutive CMV promoter, were transfected into T47D cells that express the progesterone receptor (PR or into PR-negative MDA-MB-231 cells. Results: After treatment with PROG, qPCR and Western blotting analyses indicated that BCRP mRNA and BCRP protein levels were significantly reduced in a dose-dependent manner in PR-positive cells, but PROG had no significant effect on BCRP levels in the PR-negative cells. The effect observed in PR-positive cells was reversed by co-treatment with RU-486, a specific PROG inhibitor. Cytometric analysis confirmed that BCRP-mediated drug efflux was inhibited and chemosensitivity to mitoxantrone was markedly increased by PROG treatment. Conclusion: These results suggest that PROG reverses BCRP-mediated MDR by down-regulating BCRP expression in breast cancer cells by affecting transcription from the PRE-containing BCRP promoter. Our studies suggest that breast cancer patients with BCRP-mediated MDR may be successfully treated with PROG.

  20. Radioimmunoassay for progesterone in human saliva during the menstrual cycle

    Energy Technology Data Exchange (ETDEWEB)

    Luisi, M.; Franchi, F.; Kicovic, P.M.; Silvestri, D.; Cossu, G.; Catarsi, A.L.; Barletta, D.; Gasperi, M. (Pisa Univ. (Italy))

    1981-10-01

    A sensitive, specific and accurate radioimmunoassay of progesterone in human saliva is described, using /sup 3/H. The assay had a sensitivity of 8 pg/tube and blanks were negligible. The intra- and inter-assay coefficients of variation were 5.2 and 9.4%, respectively. The mean recovery from 60 samples was 93.2 +- 6.3%. Results obtained from nine healthy, normally menstruating women showed that salivary progesterone rose from the 4th day before ovulation to a mean peak (+- SD) of 1.14 +- 0.17 ng/ml on the 8th day after ovulation, followed by a gradual decline. Correlation of salivary and simultaneously obtained plasma progesterone levels was good (r = 0.47; P < 0.001), although the maximum percent increase in salivary progesterone was more than 10 times greater than that of plasma progesterone. Salivary progesterone is thought to reflect the unbound fraction of plasma progesterone and this non-invasive technique can be used for serial investigations in which frequent samplings are required.

  1. Progesterone and Mental Rotation Task: Is There Any Effect?

    Directory of Open Access Journals (Sweden)

    Donatas Noreika

    2014-01-01

    Full Text Available Mental rotation task (MRT incorporates elements of spatial abilities, important in many professions, with people of both genders involved. Importantly, these are the areas where spatial tasks might be performed for long time periods; thus adverse effects of mental fatigue are highly unwanted. Substantial variation of MRT performance in relation to estrogen levels has been observed in many studies, whereas the role of progesterone remains elusive. Here we aimed to elucidate the effect of progesterone level on the long-duration (1.5 hours performance of MRT. We included three groups of subjects: a group of males as a control, a group of females in their follicular phase (low progesterone and a group of females in their luteal phase (high progesterone, MRT accuracy and response time, subjective fatigue ratings and cardiovascular measures together with 17β-estradiol and progesterone concentrations were analyzed. We found that subjective ratings of fatigue increased, performance accuracy increased, and mean response times decreased during the task in all groups. Females in luteal phase were significantly slower not only than men, but also than females in their follicular phase. An increase in subjective fatigue ratings was positively related to progesterone level—at higher progesterone levels, females felt more tired.

  2. Microfilter paper method for 17. cap alpha. -hydroxyprogesterone radioimmunoassay: its application for rapid screening for congenital adrenal hyperplasia. [Tritium tracer techniques

    Energy Technology Data Exchange (ETDEWEB)

    Pang, S.; Hotchkiss, J.; Drash, A.L.; Levine, L.S.; New, M.I.

    1977-11-01

    A new micromethod for measuring a steroid in blood collected on filter paper has been developed. The method is easy and rapid and has the specificity, accuracy and precision of RIA in whole plasma. Less than 20 ..mu..l of blood is required, and, therefore, samples may be obtained with heel prick. This method has been applied to the determination of 17..cap alpha..-hydroxyprogesterone (17..cap alpha..-OH-P) for screening patients with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency. There was excellent correlation (r = .94) between the values of 17..cap alpha..-OH-P obtained by microfilter paper method and those from plasma samples of cord (40 +- 13 ng/ml) and neonatal blood (<3.6 ng/ml) in normal infants. In six neonates at risk for CAH the diagnosis was made utilizing the microfilter paper method. 17..cap alpha..-OH-P concentrations were highly elevated in both filter paper eluates of whole blood (67 to 360 ng/ml of plasma) and simultaneously obtained plasma concentration (74 to 395 ng/ml) in affected infants. The concentrations of 17..cap alpha..-OH-P remained unchanged in dried filter paper blood when stored at room temperature for up to 21 days. Thus, filter paper with dried blood may be sent for steroid assay by mail. The ease with which samples may be transported and the minute amount of sample necessary make this method a promising screening test for CAH.

  3. Synthesis and evaluation of 17alpha-20E-21-(4-substituted phenyl)-19-norpregna-1,3,5(10),20-tetraene-3,17beta-diols as probes for the estrogen receptor alpha hormone binding domain.

    Science.gov (United States)

    Hanson, Robert N; Lee, Choon Young; Friel, Carolyn J; Dilis, Robert; Hughes, Alun; DeSombre, Eugene R

    2003-07-03

    As part of our program to develop probes for the hormone binding domain of the estrogen receptor alpha (ERalpha), we prepared a series of 4-para-substituted phenylvinyl estradiol derivatives using a combination of solution and solid-phase Pd(0)-catalyzed methods. The compounds 5a-j were evaluated for their binding affinity using the ERalpha hormone binding domain (HDB) isolated from transfected BL21 cells. The results indicated that although the new compounds were somewhat lower in relative binding affinity (RBA at 25 degrees C is 1-60%) than estradiol (100%), most had higher affinity than the unsubstituted parent phenylvinyl estradiol (RBA = 9%). Because the substituents did not generate a structure-activity relationship directly based on physicochemical properties, the series was evaluated using molecular modeling and molecular dynamics to determine key interactions between the ligand, especially the para substituent, and the protein. The results suggest that the observed relative binding affinities are directly related to the calculated binding energies and that amino acids juxtaposed to the para position play a significant but not dominant role in binding. In conclusion, we have identified the 17alpha-E-(4-substituted phenyl)vinyl estradiols as a class of ligands that retain significant affinity for the ERalpha-HBD. In particular, 4-substitution tends to increase receptor affinity compared to the unsubstituted analogue, as exemplified by 5e (4-COCH(3)), which had the highest RBA value (60%) of the series. Palladium(0)-catalyzed coupling reactions on solid support or in solution using suitably substituted iodo arenes and 17alpha-E-tributylstannylvinyl estradiols offer a flexible approach to their preparation. Molecular modeling studies of the receptor suggest that there exists additional ligand accessible regions within the ERalpha-HBD to generate interactions that may enhance receptor affinity or modify efficacy in developing new therapeutic agents. Studies to

  4. Prediction of ovulation in women using a rapid progesterone radioimmunoassay

    Energy Technology Data Exchange (ETDEWEB)

    Fleming, R.; Coults, J.R.T. (Glasgow Univ. (UK))

    1982-02-01

    A rapid (3-h) radioimmunoassay of plasma progesterone has been developed and used successfully to predict the time of ovulation in women undergoing artificial insemination. The results obtained using progesterone levels to date the stage of the cycle were analysed retrospectively by (1) estimation of the length of the ensuing luteal phases and comparison of these with luteal phase lengths of a control group (2) comparison of the dating using progesterone levels with retrospective determination of LH values and (3) by analysis of the dating in cycles in which conception occurred.

  5. Prior attenuation of KiSS1/GPR54 signaling in the anteroventral periventricular nucleus is a trigger for the delayed effect induced by neonatal exposure to 17alpha-ethynylestradiol in female rats.

    Science.gov (United States)

    Ichimura, Ryohei; Takahashi, Miwa; Morikawa, Tomomi; Inoue, Kaoru; Maeda, Jun; Usuda, Kento; Yokosuka, Makoto; Watanabe, Gen; Yoshida, Midori

    2015-01-01

    Neonatal exposure to 17alpha-ethynylestradiol (EE) causes delayed effect, a late-occurring irreversible damage to reproductive functions characterized by the early onset of age-matched abnormal estrous cycling. To clarify the involvement of a hypothalamic key cycling regulator KiSS1/GPR54 in the delayed effect, we investigated artificially induced LH surges and KiSS1 mRNA expression in the anteroventral periventricular nucleus (AVPV) of cycling young adult rats neonatally exposed to EE, and compared these parameters to those in about 5 months old middle-aged rats. KiSS1 mRNA expression, the number of KiSS1-positive cells and KiSS1/ERα co-expressing cells in the AVPV decreased in both EE-exposed and middle-aged rats. The peak area and levels of LH surge dose-dependently decreased in EE-exposed rats, and reduction was more evident in middle-aged rats. These results indicate that the prior attenuation of KiSS1 and consequent depression of LH surges plays a key role in the onset of abnormal estrous cycling in the delayed effect. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. Effects of 17 beta-hydroxy-17 alpha-methyl-estra-4,9,11-triene-3-one (R 1881): evidence for direct involvement of androgens in the defeminization of behaviour in rats.

    Science.gov (United States)

    Olsen, K L

    1983-09-01

    The synthetic androgen 17 beta-hydroxy-17 alpha-methyl-estra-4,9,11-triene-3-one (methyltrienolone, R 1881) binds specifically and with high affinity to androgen receptors and is presumably not metabolized into either the less potent androgens or into oestrogens. Because of these intrinsic properties, R 1881 can be used to investigate the possibility of a direct androgen involvement in the development of sexual behaviour. Females, at birth, were implanted with silicone elastomer capsules containing R 1881, testosterone, dihydrotestosterone or cholesterol for 10 days, or given daily injections of 100 micrograms hormone for 5 days. Neonatal treatment with R 1881 inhibited the capacity of female rats to show female mating behaviour when given ovarian hormones in adulthood; both implants and injections caused a similar reduction in receptive and proceptive behaviours. Testosterone, given as implants, caused almost complete defeminization, while injecting the hormone had a partial inhibition on mating responses. Dihydrotestosterone had no appreciable effect upon the development of behaviour. Thus, an androgen, R 1881, which is presumed not to be aromatized to oestrogens, has the potential to cause defeminization of mating and proceptive behaviour in female rats.

  7. Progesterone modulation of diazepam withdrawal syndrome in mice.

    Science.gov (United States)

    Pesce, M E; Acevedo, X; Pinardi, G; Miranda, H F

    1996-12-01

    The influence of progesterone and oestrogens on the benzodiazepine withdrawal syndrome in mice was studied. The intraperitoneal administration of 15 mg/kg of flumazenil induced a withdrawal syndrome in chronic diazepam-treated mice, characterized by jerks, usually accompanied by tail lifts, and seizures. The principal finding of the present work is that the intensity of diazepam withdrawal syndrome was significantly reduced by acute administration of progesterone as revealed by a low incidence of jerks and seizures. The action of progesterone could be due to a modulatory role of the hormone on neuronal activity as an anxiolytic agent. The modulatory activity of progesterone appears to be related to changes in the pharmacological properties of benzodiazepine receptors.

  8. Effect of Progesterone Therapy versus Diet Modification on ...

    African Journals Online (AJOL)

    The pathophysiology underlying functional constipation is undoubtedly, multifactorial, and not well understood. Progressively, rising progesterone and estrogen levels ... Women with endocrine disorders (hypothyroidism),. Hirschsprung's disease, spinal anomalies, anorectal pathology, inflammatory bowel disease, previous.

  9. Progesterone receptor levels independently predict survival in endometrial adenocarcinoma

    DEFF Research Database (Denmark)

    Nyholm, H C; Christensen, Ib Jarle; Nielsen, Anette Lynge

    1995-01-01

    Estrogen receptor (ER) and progesterone receptor (PR) contents were determined by biochemical (dextran charcoal-coated (DCC) assay) and immunohistochemical (ICA) methods in biopsies from 145 primary endometrial adenocarcinomas and those with eligible receptor measurements were analyzed with respect...

  10. Contraception with depot medroxy progesterone acetate (DMPA) in ...

    African Journals Online (AJOL)

    , South-South Nigeria. Cosmos E. Enyindah, Faith C. Mmom. Abstract. Clinical experience with depot medroxy progesterone acetate (DMPA) at the family planning clinic of the University of Port Harcourt Teaching Hospital st st between 1 of ...

  11. Distinct cognitive effects of estrogen and progesterone in menopausal women.

    Science.gov (United States)

    Berent-Spillson, Alison; Briceno, Emily; Pinsky, Alana; Simmen, Angela; Persad, Carol C; Zubieta, Jon-Kar; Smith, Yolanda R

    2015-09-01

    The effects of postmenopausal hormone treatment on cognitive outcomes are inconsistent in the literature. Emerging evidence suggests that cognitive effects are influenced by specific hormone formulations, and that progesterone is more likely to be associated with positive outcomes than synthetic progestin. There are very few studies of unopposed progesterone in postmenopausal women, and none that use functional neuroimaging, a sensitive measure of neurobiological function. In this study of 29 recently postmenopausal women, we used functional MRI and neuropsychological measures to separately assess the effects of estrogen or progesterone treatment on visual and verbal cognitive function. Women were randomized to receive 90 days of either estradiol or progesterone counterbalanced with placebo. After each treatment arm, women were given a battery of verbal and visual cognitive function and working memory tests, and underwent functional MRI including verbal processing and visual working memory tasks. We found that both estradiol and progesterone were associated with changes in activation patterns during verbal processing. Compared to placebo, women receiving estradiol treatment had greater activation in the left prefrontal cortex, a region associated with verbal processing and encoding. Progesterone was associated with changes in regional brain activation patterns during a visual memory task, with greater activation in the left prefrontal cortex and right hippocampus compared to placebo. Both treatments were associated with a statistically non-significant increase in number of words remembered following the verbal task performed during the fMRI scanning session, while only progesterone was associated with improved neuropsychological measures of verbal working memory compared to placebo. These results point to potential cognitive benefits of both estrogen and progesterone. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. Paraquat inhibits progesterone synthesis in human placental mitochondria.

    Science.gov (United States)

    Milczarek, Ryszard; Sokołowska, Ewa; Rybakowska, Iwona; Kaletha, Krystian; Klimek, Jerzy

    2016-07-01

    Human placenta mitochondria produces huge amounts of progesterone necessary for maintaining the pregnancy. Lipid peroxidation in human placental mitochondria inhibits progesterone synthesis and that inhibition can be reversed by superoxide dismutase and other antioxidants. Paraquat (PQ) a highly toxic herbicide generates superoxide radical inside cells and induces lipid peroxidation. Hence, it is supposed to stimulate lipid peroxidation in human placental mitochondria and in consequence to inhibit a placental mitochondrial steroidogenesis. Placentas were obtained from normal pregnancies. All experiments were done using isolated human placental mitochondria. Mitochondrial lipid peroxidation was determined as tiobarbituric acid reactive substances (TBARS). A conversion of cholesterol to pregnenolone or pregnenolone to progesterone was measured using radiolabeled steroids and thin layer chromatography. PQ enhanced the iron-dependent lipid peroxidation as also PQ heightened the inhibitory action of this process on progesterone synthesis in isolated human placental mitochondria. Paradoxically, a superoxide dismutase (SOD) reversed the inhibition of progesterone synthesis only minimally although it strongly inhibited PQ stimulated iron-dependent lipid peroxidation. When iron was absent, PQ stimulated only negligible lipid peroxidation but strongly inhibited progesterone synthesis. SOD had no effect on inhibition of progesterone synthesis by PQ. PQ strongly inhibited of the conversion of cholesterol to pregnenolone but had not got any influence on the enzymatic activity of mitochondrial 3β-hydroxysteroid dehydrogenase. PQ strongly decreased the efficiency of NADPH-dependent cytochrome P450 reduction as well as it promoted the rapid oxidation of the pre-reduced mitochondrial cytochrome P450. However PQ has not inhibited combined activity of adrenodoxin reductase and adrenodoxin. We conclude that the most important reason of the inhibition of progesterone synthesis by PQ

  13. A case of autoimmune progesterone dermatitis in an adolescent female.

    Science.gov (United States)

    Kakarla, Nirupama; Zurawin, Robert K

    2006-04-01

    Progesterone-induced dermatitis is a rare disorder. It typically occurs in females due to an autoimmune phenomenon to endogenous progesterone production, but can also be caused by exogenous intake of a synthetic progestin. Here, we present a case of autoimmune progesterone dermatitis (AIPD) seen in an adolescent female. The patient is a 15-year-old Caucasian female with no significant past medical history and no prior exogenous hormone use, who presented to her primary care physician complaining of cyclic skin eruptions. She noted that her dermatologic symptoms occurred monthly, just prior to her menses. An intradermal skin test using 0.1 cc of progesterone was performed. The patient immediately developed a wheal, confirming the diagnosis of AIPD. The patient was begun on a continuous regimen of an oral contraceptive pill with 30 micrograms of ethinyl estradiol and 0.15 mg of levonorgestrel. The skin eruptions have not returned since the initiation of this therapy. Autoimmune progesterone dermatitis manifests via the occurrence of cyclic skin eruptions. Women with the disorder commonly present with dermatologic lesions in the luteal phase of the menstrual cycle. Diagnosis of AIPD is confirmed by performing a skin allergen test using progesterone. Due to its rarity, AIPD should be considered a diagnosis of exclusion. In cases believed to be due to an endogenous production of progesterone, several methods of therapy have been attempted. The ultimate goal of therapy is the suppression of ovulation, which will prevent endogenous hormone production as progesterone is only produced in ovulatory cycles. Currently, the first-line choice of therapy is a combination oral contraceptive. If this treatment is ineffective, patients have been treated with danazol, gonadotropin releasing hormone analogs, tamoxifen, and oophorectomy with varying success.

  14. The role of progesterone in prevention of preterm birth

    Directory of Open Access Journals (Sweden)

    Jodie M Dodd

    2009-07-01

    Full Text Available Jodie M Dodd, Caroline A CrowtherDiscipline of Obstetrics and Gynaecology, The University of Adelaide, Adelaide, South Australia, AustraliaAbstract: Preterm birth continues to provide an enormous challenge in the delivery of perinatal health care, and is associated with considerable short and long-term health consequences for surviving infants. Progesterone has a role in maintaining pregnancy, by suppression of the calcium–calmodulin–myosin light chain kinase system. Additionally, progesterone has recognized anti-inflammatory properties, raising a possible link between inflammatory processes, alterations in progesterone receptor expression and the onset of preterm labor. Systematic reviews of randomized controlled trials evaluating the use of intramuscular and vaginal progesterone in women considered to be at increased risk of preterm birth have been published, with primary outcomes of perinatal death, preterm birth <34 weeks, and neurodevelopmental handicap in childhood. Eleven randomized controlled trials were included in the systematic review, involving 2714 women and 3452 infants, with results presented according to the reason women were considered to be at increased risk of preterm birth. While there is a potential beneficial effect in the use of progesterone for some women considered to be at increased risk of preterm birth, primarily in the reduction in the risk of preterm birth before 34 weeks gestation, it remains unclear if the observed prolongation of pregnancy translates into improved health outcomes for the infant.Keywords: progesterone, preterm birth, systematic review, randomized trial

  15. 17-Hydroxyprogesterone caproate to prolong pregnancy after preterm rupture of the membranes: early termination of a double-blind, randomized clinical trial

    Directory of Open Access Journals (Sweden)

    Combs C Andrew

    2011-12-01

    Full Text Available Abstract Background Progestational agents may reduce the risk of preterm birth in women with various risk factors. We sought to test the hypothesis that a weekly dose of 17-hydroxyprogesterone caproate (17P given to women with preterm rupture of the membranes (PROM will prolong pregnancy and thereby reduce neonatal morbidity. Methods Double-blind, placebo-controlled randomized clinical trial. Women with PROM at 23.0 to 31.9 weeks of gestation were randomly assigned to receive a weekly intramuscular injection of 17P (250 mg in 1 mL castor oil or placebo (1 mL castor oil. The primary outcome was the rate of continuing the pregnancy until 34.0 weeks of gestation or until documentation of fetal lung maturity at 32.0 to 33.9 weeks of gestation. Planned secondary outcomes were duration of latency period and rate of composite neonatal morbidity. Enrollment of 111 participants per group, 222 total, was planned to yield 80% power to detect an increase in the primary outcome from 30% with placebo to 50% with 17P. Results Twelve women were enrolled of whom 4 were randomly assigned to receive 17P and 8 to receive placebo. The trial was terminated prematurely because of two separate issues related to the supply of 17P. No adverse events attributable to 17P were identified. Conclusion Because of premature termination, the trial does not have adequate statistical power to evaluate efficacy or safety of 17P in women with PROM. Nonetheless, ethical principles dictate that we report the results, which may contribute to possible future metaanalyses and systematic reviews. Trial Registration ClinicalTrials.gov: NCT01119963 Supported by a research grant from the Center for Research, Education, and Quality, Pediatrix Medical Group, Sunrise, FL

  16. Reference ranges of 17-hydroxyprogesterone, DHEA, DHEAS, androstenedione, total and free testosterone determined by TurboFlow-LC-MS/MS and associations to health markers in 304 men.

    Science.gov (United States)

    Damgaard-Olesen, A; Johannsen, T H; Holmboe, S A; Søeborg, T; Petersen, J H; Andersson, Am; Aadahl, M; Linneberg, A; Juul, A

    2016-02-15

    We report reference ranges based on LC-MS/MS for testosterone (T), free testosterone (FT) and its precursors, i.e. 17-hydroxyprogesterone (17-OHP), dehydroepiandrosterone (DHEA), DHEA-sulfate (DHEAS) and androstenedione (Adione), in relation to different health markers and lifestyle factors. The study was based on 304 healthy men aged 30-61 years participating in a population-based cross-sectional study (Health2008). Examination program consisted of a clinical examination, completion of a self-administered questionnaire and blood sampling. Steroid metabolites were measured by a validated and sensitive LC-MS/MS method. Older age-groups were significantly associated with decreased concentrations of DHEA, DHEAS, Adione, and FT, while no significant associations with age were shown for 17-OHP or T. Participants with BMI≥30 kg/m(2) had lower age-related steroid metabolite z-scores compared to participants with BMI<30 kg/m(2), i.e. 17-OHP: -0.51 vs. 0.08 (p<0.001); DHEA: -0.27 vs. 0.09 (p=0.014); Adione: -0.29 vs. 0.09 (p=0.012); T: -0.99 vs. 0.14 (p<0.001); and FT -0.55 vs. 0.05 (p<0.001), respectively. In conclusion, this large study on serum steroid metabolites and concomitant assessment of health markers in healthy men provides age-related reference ranges, and furthermore evaluates the impact of lifestyle factors and metabolic syndrome on androgen metabolite levels. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. Determination of estriol, estradiol, estrone, and progesterone in cosmetic products.

    Science.gov (United States)

    Hubinger, Jean C

    2015-01-01

    This report describes the development and validation of a reverse phase high-performance liquid chromatography (HPLC) method with UV detection for the determination of the hormones estriol, estradiol, estrone, and progesterone in topically applied products. The developed method was then used to conduct a postmarket survey of consumer products for these hormones. Each product was first mixed with Celite and then extracted with methanol. Extracts were cleaned on a Waters Oasis HLB solid phase extraction cartridge, and then analyzed using reversed phase HPLC. The analytes were separated using an Agilent Zorbax Eclipse XDB C8 (5 μm, 250 mm by 4.6 mm) analytical column and detected by their absorbance at 230 nm. Chromatographic separation was achieved by a 1.0-ml/min linear gradient from 30% acetonitrile and 70% water to 80% acetonitrile and 20% water over 30 min. A final 5 min hold time and a re-equilibration time of 10 min were used to prepare the column for subsequent analysis. Recovery from two different brand lotions spiked with three different levels of estriol, estradiol, estrone, and progesterone ranged from 81.8% to 101%. In this study, a total of 70 cosmetic products were surveyed. Twenty two (63%) of the 35 products were labeled as containing an estrogen and/ or progesterone and also provided quantitative label information about the hormone ingredient. The most frequently labeled hormones were progesterone (66%), estriol (46%), estradiol (11%), and estrone (6%). Six products labeled as containing estriol were found to contain estradiol. An estrogen and/or progesterone were found in 34 products at concentrations ranging from 86.0 to 26,800 μg/g. Progesterone was not found in one product labeled as containing this hormone. An additional 35 products, which did not list hormones on their labels, were analyzed and estrogen or progesterone was not detected in these products.

  18. Evaluation of clinical evidences for progesterone therapy in catamenial epilepsy

    Directory of Open Access Journals (Sweden)

    Tao CHEN

    2014-12-01

    Full Text Available Objective To formulate the best treatment plan for catamenial epilepsy patients by evaluating the efficacy and side effect of progesterone therapy via evidence-based medicine.  Methods Catamenial epilepsy, drug therapy, progesterone, allopregnanolone, systematic review and randomized controlled trial (RCT both in Chinese and English were used as retrieval words. Databases including Wanfang Data, VIP, China National Knowledge Infrastructure (CNKI, Cochrane Library, PubMed and Google Scholar were used with applying of manual searching. Systematic reviews, RCTs, open-label trials, prospective and retrospective case analysis, case-observation studies and reviews were collected and evaluated by Jadad Scale.  Results After screening, 18 relevant resources were selected, including one systematic review, 3 RCTs, one open-label trial, 2 prospective case-controlled studies, one follow-up study and 10 reviews. Ten of the articles were evaluated to be high quality (Jadad Scale score ≥ 4, and the other 8 were of low quality (Jadad Scale score < 4. After the efficacy and safety of those clinical studies were evaluated, the results were summarized as follows: 1 progesterone combined with antiepileptic drugs (AEDs was well tolerated and resulted in a significant reduction of seizure frequency in a majority of patients with catamenial epilepsy. 2 Both natural progesterone and synthetic progesterone could be used in the treatment for catamenial epilepsy. 3 There were two ways of progestogen therapy for catamenial epilepsy: cyclical progesterone hormone therapy and suppressive therapy. The former was more commonly used.  Conclusions Using evidence-based medicine evaluation can provide best clinical evidence for the progesterone treatment on catamenial epilepsy. doi: 10.3969/j.issn.1672-6731.2014.12.007

  19. Influence of monoolein on progesterone transdermal delivery

    Directory of Open Access Journals (Sweden)

    Wanessa de Souza Cardoso Quintão

    2015-12-01

    Full Text Available abstract This work aimed to investigate in vitro the influence of monoolein (MO on progesterone (PG transdermal delivery and skin retention. Information about the role of MO as an absorption enhancer for lipophilic molecules can help on innovative product development capable of delivering the hormone through the skin in a consistent manner, improving transdermal therapy of hormonal replacement. MO was dispersed in propylene glycol under heat at concentrations of 0% (control, 5% w/w, 10% w/w and 20% w/w. Then, 0.6% of PG (w/w was added to each formulation. Permeation profile of the hormone was determined in vitro for 48 h using porcine skin in Franz diffusion cells. PG permeation doubled when 5% (w/w of MO was present in formulation in comparison to both the control and higher MO concentrations (10% and 20% w/w. An equal trend was observed for PG retention in stratum corneum (SC and reminiscent skin (E+D. PG release rates from the MO formulations, investigated using cellulose membranes, revealed that concentrations of MO higher than 5% (w/w hindered PG release, which indeed negatively reflected on the hormone permeation through the skin. In conclusion, this work demonstrated the feasibility of MO addition (at 5% w/w in formulations as a simple method to increase transdermal PG delivery for therapies of hormonal replacement. In contrast, higher MO concentrations (from 10% to 20% w/w can control active release, and this approach could be extrapolated to other lipophilic, low-molecular-weight molecules.

  20. Immunohistochemical Expression of Estrogen and Progesterone Receptors in Epulis Fissuratum

    Directory of Open Access Journals (Sweden)

    Maryam Seyedmajidi

    2013-01-01

    Full Text Available Background: Epulis Fissuratum (Epulis Fissuratum (EF or Denture Epulis or inflammatory fibrous hyperplasia is a common hyperplastic tumor-like lesion with reactive nature, related to loose and ill-fitting, full or partial removable dentures and it is more common in women than men. For this reason, hormonal influences may also play role in its creation. The effect of steroid hormones especially sex hormones (Estrogen and progesterone on oral mucosa is identified in some studies. In the present study, the distribution pattern and presence of estrogen and progesterone receptors in epithelial, stromal, endothelial and inflammatory cells in Epulis Fissuratum was investigated. Materials and Methods: This cross-sectional study was carried out on 30 samples of paraffin blocks with Epulis Fissuratum diagnosis and 30 samples of normal mucosal tissues as a control group who have had surgery as a margin beside the above lesions and had been obtained from the oral and maxillofacial pathology departement of Babol Dental School since 2003 up to 2010. Intensity of staining and immunoreactivity were evaluated using subjective index and considering the positive control group (breast carcinoma.Results: Epithelial, stromal, endothelial and inflammatory cells didn’t show reaction with monoclonal antibodies against estrogen and progesterone in none of the samples. Conclusion: It seems that the hypothesis of the existence of estrogen and progesterone receptors in epulis fissuratum and normal oral mucosa is ruled out. The possibility of direct effect of estrogen and progesterone in occurring of epulis fissuratum is rejected.

  1. Distribution of estrogen and progesterone receptors in Epulis Fissuratum

    Directory of Open Access Journals (Sweden)

    Shahrabi Sh.

    2005-06-01

    Full Text Available Statement of Problem: Epulides Fissurata (EF are common proliferative and denture- induced lesions of the oral cavity with a predilection for female. This suggests a possible role for sex steroid hormones in the development and progression of these lesions. Purpose: The objective of this study was the immunohistochemical evaluation of epulis fissuratum of the oral cavity for estrogen and progesterone receptors expression in epithelial, stromal, inflammatory and endothelial cells populations. Materials and Methods: In this cross-sectional study, 15 samples of formalin- fixed, paraffin- embedded epulis fissuratums including marginal mucosal tissues in 4 cases as a control group, were immuno-histochemically evaluated for estrogen and progesterone receptors protein expression. Result: In 10 cases, estrogen receptor positivity was found within the epithelium and progesterone receptor immunoreactivity was present in 7 cases. Stromal cells exhibited estrogen and progesterone receptor immunostaining in many cases but only few cases showed expression of these receptors in the inflammatory and endothelial cells. Estrogen and progesterone receptors were also detected in some cases containing salivary glands tissue. Conclusion: Although chronic irritation may be the initiating factor for the occurence of epulis fissuratum, some of the cells in the lesion, could be potential targets for estrogen and progestrone hormones.

  2. Comparison of pregnancy rates with intramuscular and vaginal progesterone use for luteal phase support in intracytoplasmic sperm injection cycles

    Directory of Open Access Journals (Sweden)

    Murat Isikalan

    2016-12-01

    Conclusion: The results of vaginal progesterone administration were similar with the results obtained with intramuscular progesterone. Vaginal progesterone use is a more tolerable method for patients. [Cukurova Med J 2016; 41(4.000: 639-647

  3. Use of Progesterone Treatment for the Prevention of Recurrent Preterm Birth: Identification of Obstacles to Change

    NARCIS (Netherlands)

    Lim, Arianne C.; Goossens, Astrid; Ravelli, Anita C. J.; Boer, Kees; Bruinse, Hein W.; Mol, Ben Willem J.

    2010-01-01

    Progesterone treatment has proven to be effective in preventing recurrent preterm birth. The use of progesterone varies widely between different obstetric clinics in the Netherlands. The study aimed to identify factors that hamper or facilitate the use of progesterone to create an implementation

  4. Milk progesterone on day 5 following insemination in the dairy cow ...

    African Journals Online (AJOL)

    Despite the importance of progesterone on the fertility of lactating dairy cows, the factors that affect post ovulatory progesterone concentration are still unclear. Thus, the aim of the present study was to identify factors associated with the post ovulatory progesterone rise following 1st insemination in lactating dairy cows.

  5. Fabrication of Progesterone-Loaded Nanofibers for the Drug Delivery Applications in Bovine

    Science.gov (United States)

    Karuppannan, Chitra; Sivaraj, Mehnath; Kumar, J. Ganesh; Seerangan, Rangasamy; Balasubramanian, S.; Gopal, Dhinakar Raj

    2017-02-01

    Progesterone is a potent drug for synchronization of the estrus and ovulation cycles in bovine. At present, the estrus cycle of bovine is controlled by the insertion of progesterone-embedded silicone bands. The disadvantage of nondegradable polymer inserts is to require for disposal of these bands after their use. The study currently focuses on preparation of biodegradable progesterone-incorporated nanofiber for estrus synchronization. Three different concentrations (1.2, 1.9, and 2.5 g) of progesterone-impregnated nanofibers were fabricated using electrospinning. The spun membrane were characterized by scanning electron microscopy, X-ray diffraction, differential scanning calorimetry, thermogravimetric analysis, and Fourier transform infrared spectroscopy. Uniform surface morphology, narrow size distribution, and interaction between progesterone and zein were confirmed by SEM. FTIR spectroscopy indicated miscibility and interaction between zein and progesterone. X-ray analysis indicated that the size of zein crystallites increased with progesterone content in nanofibers. Significant differences in thermal behavior of progesterone-impregnated nanofiber were observed by DSC. Cell viability studies of progesterone-loaded nanofiber were examined using MTT assay. In vitro release experiment is to identify the suitable progesterone concentration for estrus synchronization. This study confirms that progesterone-impregnated nanofibers are an ideal vehicle for progesterone delivery for estrus synchronization of bovines.

  6. Progesterone profiles of postpartum dairy cows as an aid to ...

    African Journals Online (AJOL)

    insemination. It was concluded that repeat breeding could be due to several reasons, only some of which could be identified from progesterone profiles. Daaglikse melkprogesteroonwaardes van 44 melkkoeie is bepaal vanaf kalwing tot besetting sodat progesteroon- profiele gebruik kon word om voortplantingsgebreke.

  7. Effects of progesterone injection on performance, plasma hormones ...

    African Journals Online (AJOL)

    An experiment was conducted to evaluate responses of feed-satiated and feed- restricted breeder hens to daily injection of progesterone (P4). A total of 64 Cobb 500 hens were fed either restricted or ad libitum from 27 to 38 wk of age. Fourteen laying hens from each group were selected to conduct P4 injection assay.

  8. Effect of exogenous progesterone on oestrus response of West ...

    African Journals Online (AJOL)

    SERVER

    2008-01-04

    Jan 4, 2008 ... 1Department of Veterinary Physiology, Pharmacology and Biochemistry, College of Veterinary Medicine, University of. Agriculture, PMB 2373 ... progesterone treatments and 1.0 ml physiological saline as the control. The animals were ... are more researches on goat reproduction and manage- ment in ...

  9. Effects of progesterone injection on performance, plasma hormones ...

    African Journals Online (AJOL)

    PRECIOUS

    2009-11-16

    Nov 16, 2009 ... steroid hormones (P4, E2 and testosterone) and regres- sed ovary. Progesterone injection increased numbers of hens holding a hard-shelled egg in their uterus. Proges- terone injection had no significant effect on glucose home ostasis and lipid metabolism. Restricted fed and laying ad libitum fed breeder ...

  10. Effect of Exogenous Progesterone on Testes Characteristics of ...

    African Journals Online (AJOL)

    The parameters measured include seminiferous tubule diameter, paired testes weight (PTW), testis density, Daily sperm production (DSP) from gonadal sperm reserves (GSR) and DSP from quantitative testicular histology (QTH). The results show that progesterone significantly (P<0.05) increased the values of DSP from ...

  11. Long-term effects of prenatal progesterone exposure

    DEFF Research Database (Denmark)

    Vedel, C.; Larsen, H.; Holmskov, Anni

    2016-01-01

    children from 498 twin pregnancies, were followed-up. PREDICT was a placebo-controlled randomized clinical trial examining the effect of progesterone for prevention of preterm delivery in unselected twin pregnancies. Medical histories of the children were reviewed and neurophysiological development...

  12. 21 CFR 862.1620 - Progesterone test system.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Progesterone test system. 862.1620 Section 862.1620 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... in the diagnosis and treatment of disorders of the ovaries or placenta. (b) Classification. Class I...

  13. Rodent Models of Non-classical Progesterone Action Regulating Ovulation

    Directory of Open Access Journals (Sweden)

    Melinda A. Mittelman-Smith

    2017-07-01

    Full Text Available It is becoming clear that steroid hormones act not only by binding to nuclear receptors that associate with specific response elements in the nucleus but also by binding to receptors on the cell membrane. In this newly discovered manner, steroid hormones can initiate intracellular signaling cascades which elicit rapid effects such as release of internal calcium stores and activation of kinases. We have learned much about the translocation and signaling of steroid hormone receptors from investigations into estrogen receptor α, which can be trafficked to, and signal from, the cell membrane. It is now clear that progesterone (P4 can also elicit effects that cannot be exclusively explained by transcriptional changes. Similar to E2 and its receptors, P4 can initiate signaling at the cell membrane, both through progesterone receptor and via a host of newly discovered membrane receptors (e.g., membrane progesterone receptors, progesterone receptor membrane components. This review discusses the parallels between neurotransmitter-like E2 action and the more recently investigated non-classical P4 signaling, in the context of reproductive behaviors in the rodent.

  14. Progesterone Regulation of Synaptic Transmission and Plasticity in Rodent Hippocampus

    Science.gov (United States)

    Foy, Michael R.; Akopian, Garnik; Thompson, Richard F.

    2008-01-01

    Ovarian hormones influence memory formation by eliciting changes in neural activity. The effects of various concentrations of progesterone (P4) on synaptic transmission and plasticity associated with long-term potentiation (LTP) and long-term depression (LTD) were studied using in vitro hippocampal slices. Extracellular studies show that the…

  15. Characterization of the Ca2+ Channels Involved in the Progesterone ...

    African Journals Online (AJOL)

    There is evidence that intracellular Ca2+ concentration plays significant roles in sperm function such as motility and acrosome reaction. Many calcium channels have been identified in the plasma membrane of sperm. Progesterone (P4) stimulates Ca2+ influx and acrosome reaction in human spermatozoa. The effects of ...

  16. Protective actions of progesterone in the cardiovascular system: potential role of membrane progesterone receptors (mPRs) in mediating rapid effects.

    Science.gov (United States)

    Thomas, Peter; Pang, Yefei

    2013-06-01

    The protective functions of progesterone in the cardiovascular system have received little attention even though evidence has accumulated that progesterone lowers blood pressure, inhibits coronary hyperactivity and has powerful vasodilatory and natriuretic effects. One possible reason why potential beneficial actions of progesterone on cardiovascular functions have not been extensively studied is that divergent effects to those of progesterone have been observed in many clinical trials with synthetic progestins such as medroxyprogesterone acetate which are associated with increased risk of coronary disease. Evidence that progesterone exerts protective effects on cardiovascular functions is briefly reviewed. The finding that progesterone administration decreases blood vessel vasoconstriction in several animal models within a few minutes suggests that rapid, nongenomic progesterone mechanisms are of physiological importance in regulating vascular tone. Rapid activation of second messenger pathways by progesterone has been observed in vascular endothelial and smooth muscle cells, resulting in alterations in endothelial nitric oxide synthase (eNOS) activity and calcium influx, respectively. Both nuclear progesterone receptors (PRs) and novel membrane progesterone receptors (mPRs) are candidates for the intermediaries in these rapid, cell-surface initiated progesterone actions in endothelial and smooth muscle vascular cells. PRs have been detected in both cell types. New data are presented showing mPRα, mPRβ and mPRγ are also present in human endothelial and smooth muscle vascular cells. Preliminary evidence suggests mPRs mediate rapid progestin signaling in these endothelial cells, resulting in down-regulation of cAMP production and increased nitric oxide synthesis. The role of mPRs in progesterone regulation of cardiovascular functions warrants further investigation. Copyright © 2013 Elsevier Inc. All rights reserved.

  17. Progesterone stimulates adipocyte determination and differentiation 1/sterol regulatory element-binding protein 1c gene expression. potential mechanism for the lipogenic effect of progesterone in adipose tissue.

    Science.gov (United States)

    Lacasa, D; Le Liepvre, X; Ferre, P; Dugail, I

    2001-04-13

    Fatty acid synthase (FAS), a nutritionally regulated lipogenic enzyme, is transcriptionally controlled by ADD1/SREBP1c (adipocyte determination and differentiation 1/sterol regulatory element-binding protein 1c), through insulin-mediated stimulation of ADD1/SREBP1c expression. Progesterone exerts lipogenic effects on adipocytes, and FAS is highly induced in breast tumor cell lines upon progesterone treatment. We show here that progesterone up-regulates ADD1/SREBP1c expression in the MCF7 breast cancer cell line and the primary cultured preadipocyte from rat parametrial adipose tissue. In MCF7, progesterone induced ADD1/SREBP1c and Metallothionein II (a well known progesterone-regulated gene) mRNAs, with comparable potency. In preadipocytes, progesterone increased ADD1/SREBP1c mRNA dose-dependently, but not SREBP1a or SREBP2. Run-on experiments demonstrated that progesterone action on ADD1/SREBP1c was primarily at the transcriptional level. The membrane-bound and mature nuclear forms of ADD1/SREBP1 protein accumulated in preadipocytes cultured with progesterone, and FAS induction could be abolished by adenovirus-mediated overexpression of a dominant negative form of ADD1/SREBP1 in these cells. Finally, in the presence of insulin, progesterone was unable to up-regulate ADD1/SREBP1c mRNA in preadipocytes, whereas its effect was restored after 24 h of insulin deprivation. Together these results demonstrate that ADD1/SREBP1c is controlled by progesterone, which, like insulin, acts by increasing ADD1/SREBP1c gene transcription. This provides a potential mechanism for the lipogenic actions of progesterone on adipose tissue.

  18. Sex, age, pubertal development and use of oral contraceptives in relation to serum concentrations of DHEA, DHEAS, 17α-hydroxyprogesterone, Δ4-androstenedione, testosterone and their ratios in children, adolescents and young adults

    DEFF Research Database (Denmark)

    Søeborg, Tue; Frederiksen, Hanne; Mouritsen, Annette

    2014-01-01

    serum samples from healthy children, adolescents and young adults was evaluated. Samples were analyzed by Turboflow-LC-MS/MS. Sex hormone-binding globulin was analyzed by immunoassay. All steroid metabolite concentrations were positively associated with age and pubertal development in both sexes......The influence of sex, age, pubertal development and oral contraceptives on dehydroepiandrosterone (DHEA), DHEA sulfate (DHEAS), 17α-hydroxyprogesterone (17-OHP), Δ4-androstenedione (Adione), testosterone (T), calculated free testosterone (fT), free androgen index (FAI) and selected ratios in 1798...... to sex, age and pubertal development. Use of oral contraceptives strongly influences adrenal steroidogenesis and should be considered when diagnosing and monitoring treatment of patients with disorders of sex development....

  19. A prospective randomized multicentre study comparing vaginal progesterone gel and vaginal micronized progesterone tablets for luteal support after in vitro fertilization/intracytoplasmic sperm injection

    DEFF Research Database (Denmark)

    Bergh, Christina; Lindenberg, Svend; Al Humaidan, Peter Samir Heskjær

    2012-01-01

    SUMMARY QUESTION: Is vaginal progesterone gel equivalent to vaginal micronized progesterone tablets concerning ongoing pregnancy rate and superior concerning patient convenience when used for luteal support after IVF/ICSI? SUMMARY ANSWER: Equivalence of treatments in terms of ongoing live intraut...

  20. Stress-induced progesterone secretion and progesterone receptor immunoreactivity in the paraventricular nucleus are modulated by pubertal development in male rats.

    Science.gov (United States)

    Romeo, Russell D; Bellani, Rudy; McEwen, Bruce S

    2005-12-01

    Male rats show a differential adrenocortical response to stress before and after pubertal development, such that prepubertal animals have a more prolonged stress-induced corticosterone response compared to adults. Whether pubertal maturation affects other adrenocortical responses to stress is currently unknown. To address this question, we assessed stress-induced progesterone secretion in both intact and gonadectomized prepubertal (28 days of age) and adult (77 days of age) male rats either before or after exposure to a 30 min session of restraint stress. We found that prepubertal males show a greater and more prolonged stress-induced progesterone response compared to adults. We also found a similar effect in castrated prepubertal and adult males, indicating the differential stress-induced progesterone response is not gonadal in origin. We also examined progesterone receptor (PR) levels by immunohistochemistry in the paraventricular nucleus (PVN) of the hypothalamus, a key regulatory nucleus of the hypothalamic-pituitary-adrenal (HPA) axis, and found lower PR protein expression in the PVN of prepubertal compared to adult males. These data indicate that in addition to corticosterone, stress-induced adrenocortical progesterone levels are differentially affected by pubertal maturation. Furthermore, these data raise the possibility of different progesterone sensitivity of the PVN before and after puberty. The significance of this differential response is presently unknown. However, given the pleiotropic effects of progesterone on male physiology and behaviour, it is likely that the disparate post-stress exposure to progesterone affects the prepubertal and adult male differently.

  1. Progesterone and the Latency Period: Threatened Preterm Labor

    Directory of Open Access Journals (Sweden)

    S Borna

    2008-06-01

    Full Text Available Background: Preterm labor is a major contributor to neonatal morbidity and mortality and results in increased obstetric and pediatric care costs. The purpose of this study was to assess the effects of vaginal progesterone for maintenance therapy following treatment of threatened preterm labor for preventing preterm birth.Methods: The study included 70 singleton pregnant women with preterm labor with intact membranes. Patients were randomized to receive either maintenance vaginal progesterone therapy (n=37 administered (400 mg daily or no treatment (controls, n=33 after discontinuation of acute intravenous tocolysis.Results: The two groups were similar with at respect to maternal age, race, parity, gestational age at admission, bishop score, and preterm delivery risk factors .Compared to the control group, the mean ±SD time gained from initiation of maintenance therapy to delivery (36/1117/9 versus 24/5227/2 (meanSD days, p=0.037 and the gestational age at delivery (36.071.56 vs. 34.51.3 weeks, p=0.041 were higher in the vaginal progesterone maintenance therapy group. No significant differences were found with recurrent preterm labor 13 (35.1% versus 19 (57.6%, p=0.092. Respiratory distress syndrome 4 (10.8% versus 12 (36.4% p=0.021, Low birth weight10 (27% versus, 17 (51.5% p=0.04, birth weight (3101.54±587.9gr versus r 2609.39±662.9gr, p=0.002 were significantly different between the two groups.Conclusion: The gestational age and time gained from initiation of maintenance therapy to delivery were longer in women receiving vaginal maintenance tocolysis with progesterone and improve perinatal outcomes. However, maintenance therapy did not decrease the recurrence of preterm labor episodes.

  2. Improving the developability profile of pyrrolidine progesterone receptor partial agonists

    Energy Technology Data Exchange (ETDEWEB)

    Kallander, Lara S.; Washburn, David G.; Hoang, Tram H.; Frazee, James S.; Stoy, Patrick; Johnson, Latisha; Lu, Qing; Hammond, Marlys; Barton, Linda S.; Patterson, Jaclyn R.; Azzarano, Leonard M.; Nagilla, Rakesh; Madauss, Kevin P.; Williams, Shawn P.; Stewart, Eugene L.; Duraiswami, Chaya; Grygielko, Eugene T.; Xu, Xiaoping; Laping, Nicholas J.; Bray, Jeffrey D.; Thompson, Scott K. (GSKPA)

    2010-09-17

    The previously reported pyrrolidine class of progesterone receptor partial agonists demonstrated excellent potency but suffered from serious liabilities including hERG blockade and high volume of distribution in the rat. The basic pyrrolidine amine was intentionally converted to a sulfonamide, carbamate, or amide to address these liabilities. The evaluation of the degree of partial agonism for these non-basic pyrrolidine derivatives and demonstration of their efficacy in an in vivo model of endometriosis is disclosed herein.

  3. Progesterone Action in Endometrial Cancer, Endometriosis, Uterine Fibroids, and Breast Cancer

    Science.gov (United States)

    Kim, J. Julie; Kurita, Takeshi

    2013-01-01

    Progesterone receptor (PR) mediates the actions of the ovarian steroid progesterone, which together with estradiol regulates gonadotropin secretion, prepares the endometrium for implantation, maintains pregnancy, and differentiates breast tissue. Separation of estrogen and progesterone actions in hormone-responsive tissues remains a challenge. Pathologies of the uterus and breast, including endometrial cancer, endometriosis, uterine fibroids, and breast cancer, are highly associated with estrogen, considered to be the mitogenic factor. Emerging evidence supports distinct roles of progesterone and its influence on the pathogenesis of these diseases. Progesterone antagonizes estrogen-driven growth in the endometrium, and insufficient progesterone action strikingly increases the risk of endometrial cancer. In endometriosis, eutopic and ectopic tissues do not respond sufficiently to progesterone and are considered to be progesterone-resistant, which contributes to proliferation and survival. In uterine fibroids, progesterone promotes growth by increasing proliferation, cellular hypertrophy, and deposition of extracellular matrix. In normal mammary tissue and breast cancer, progesterone is pro-proliferative and carcinogenic. A key difference between these tissues that could explain the diverse effects of progesterone is the paracrine interactions of PR-expressing stroma and epithelium. Normal endometrium is a mucosa containing large quantities of distinct stromal cells with abundant PR, which influences epithelial cell proliferation and differentiation and protects against carcinogenic transformation. In contrast, the primary target cells of progesterone in the breast and fibroids are the mammary epithelial cells and the leiomyoma cells, which lack specifically organized stromal components with significant PR expression. This review provides a unifying perspective for the diverse effects of progesterone across human tissues and diseases. PMID:23303565

  4. Progesterone modulates microtubule dynamics and epiboly progression during zebrafish gastrulation.

    Science.gov (United States)

    Eckerle, Stephanie; Ringler, Mario; Lecaudey, Virginie; Nitschke, Roland; Driever, Wolfgang

    2017-12-26

    Control of microtubule dynamics is crucial for cell migration. We analyzed regulation of microtubule network dynamics in the zebrafish yolk cell during epiboly, the earliest coordinated gastrulation movement. We labeled microtubules with EMTB-3GFP and EB3-mCherry to visualize and measure microtubule dynamics by TIRF microscopy live imaging. Yolk cell microtubules dynamics is temporally modulated during epiboly progression. We used maternal zygotic Pou5f3 mutant (MZspg) embryos, which develop strong distortions of microtubule network organization and epiboly retardation, to investigate genetic control of microtubule dynamics. In MZspg embryos, microtubule plus-end growth tracks move slower and are less straight compared to wild-type. MZspg embryos have altered steroidogenic enzyme expression, resulting in increased pregnenolone and reduced progesterone levels. We show that progesterone positively affects microtubule plus-end growth and track straightness. Progesterone may thus act as a non-cell-autonomous regulator of microtubule dynamics across the large yolk cell, and may adjust differing demands on microtubule dynamics and stability during initiation and progression phases of epiboly. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Progesterone is essential for protecting against LPS-induced pregnancy loss. LIF as a potential mediator of the anti-inflammatory effect of progesterone.

    Directory of Open Access Journals (Sweden)

    Julieta Aisemberg

    Full Text Available Lipopolysaccharide (LPS administration to mice on day 7 of gestation led to 100% embryonic resorption after 24 h. In this model, nitric oxide is fundamental for the resorption process. Progesterone may be responsible, at least in part, for a Th2 switch in the feto-maternal interface, inducing active immune tolerance against fetal antigens. Th2 cells promote the development of T cells, producing leukemia inhibitory factor (LIF, which seems to be important due to its immunomodulatory action during early pregnancy. Our aim was to evaluate the involvement of progesterone in the mechanism of LPS-induced embryonic resorption, and whether LIF can mediate hormonal action. Using in vivo and in vitro models, we provide evidence that circulating progesterone is an important component of the process by which infection causes embryonic resorption in mice. Also, LIF seems to be a mediator of the progesterone effect under inflammatory conditions. We found that serum progesterone fell to very low levels after 24 h of LPS exposure. Moreover, progesterone supplementation prevented embryonic resorption and LPS-induced increase of uterine nitric oxide levels in vivo. Results show that LPS diminished the expression of the nuclear progesterone receptor in the uterus after 6 and 12 h of treatment. We investigated the expression of LIF in uterine tissue from pregnant mice and found that progesterone up-regulates LIF mRNA expression in vitro. We observed that LIF was able to modulate the levels of nitric oxide induced by LPS in vitro, suggesting that it could be a potential mediator of the inflammatory action of progesterone. Our observations support the view that progesterone plays a critical role in a successful pregnancy as an anti-inflammatory agent, and that it could have possible therapeutic applications in the prevention of early reproductive failure associated with inflammatory disorders.

  6. Progesterone inhibits epithelial-to-mesenchymal transition in endometrial cancer.

    Directory of Open Access Journals (Sweden)

    Paul H van der Horst

    Full Text Available BACKGROUND: Every year approximately 74,000 women die of endometrial cancer, mainly due to recurrent or metastatic disease. The presence of tumor infiltrating lymphocytes (TILs as well as progesterone receptor (PR positivity has been correlated with improved prognosis. This study describes two mechanisms by which progesterone inhibits metastatic spread of endometrial cancer: by stimulating T-cell infiltration and by inhibiting epithelial-to-mesenchymal cell transition (EMT. METHODOLOGY AND PRINCIPAL FINDINGS: Paraffin sections from patients with (n = 9 or without (n = 9 progressive endometrial cancer (recurrent or metastatic disease were assessed for the presence of CD4+ (helper, CD8+ (cytotoxic and Foxp3+ (regulatory T-lymphocytes and PR expression. Progressive disease was observed to be associated with significant loss of TILs and loss of PR expression. Frozen tumor samples, used for genome-wide expression analysis, showed significant regulation of pathways involved in immunesurveillance, EMT and metastasis. For a number of genes, such as CXCL14, DKK1, DKK4, PEG10 and WIF1, quantitive RT-PCR was performed to verify up- or downregulation in progressive disease. To corroborate the role of progesterone in regulating invasion, Ishikawa (IK endometrial cancer cell lines stably transfected with PRA (IKPRA, PRB (IKPRB and PRA+PRB (IKPRAB were cultured in presence/absence of progesterone (MPA and used for genome-wide expression analysis, Boyden- and wound healing migration assays, and IHC for known EMT markers. IKPRB and IKPRAB cell lines showed MPA induced inhibition of migration and loss of the mesenchymal marker vimentin at the invasive front of the wound healing assay. Furthermore, pathway analysis of significantly MPA regulated genes showed significant down regulation of important pathways involved in EMT, immunesuppression and metastasis: such as IL6-, TGF-β and Wnt/β-catenin signaling. CONCLUSION: Intact progesterone signaling in non

  7. Progesterone Induces Scolex Evagination of the Human Parasite Taenia solium: Evolutionary Implications to the Host-Parasite Relationship

    Science.gov (United States)

    Escobedo, Galileo; Camacho-Arroyo, Ignacio; Hernández-Hernández, Olivia Tania; Ostoa-Saloma, Pedro; García-Varela, Martín; Morales-Montor, Jorge

    2010-01-01

    Taenia solium cysticercosis is a health problem in underdeveloped and developed countries. Sex hormones are involved in cysticercosis prevalence in female and male pigs. Here, we evaluated the effects of progesterone and its antagonist RU486 on scolex evagination, which is the initial step in the development of the adult worm. Interestingly, progesterone increased T. solium scolex evagination and worm growth, in a concentration-independent pattern. Progesterone effects could be mediated by a novel T. solium progesterone receptor (TsPR), since RU486 inhibits both scolex evagination and worm development induced by progesterone. Using RT-PCR and western blot, sequences related to progesterone receptor were detected in the parasite. A phylogenetic analysis reveals that TsPR is highly related to fish and amphibian progesterone receptors, whereas it has a distant relation with birds and mammals. Conclusively, progesterone directly acts upon T. solium cysticerci, possibly through its binding to a progesterone receptor synthesized by the parasite. PMID:20037735

  8. Progesterone Induces Scolex Evagination of the Human Parasite Taenia solium: Evolutionary Implications to the Host-Parasite Relationship

    Directory of Open Access Journals (Sweden)

    Galileo Escobedo

    2010-01-01

    Full Text Available Taenia solium cysticercosis is a health problem in underdeveloped and developed countries. Sex hormones are involved in cysticercosis prevalence in female and male pigs. Here, we evaluated the effects of progesterone and its antagonist RU486 on scolex evagination, which is the initial step in the development of the adult worm. Interestingly, progesterone increased T. solium scolex evagination and worm growth, in a concentration-independent pattern. Progesterone effects could be mediated by a novel T. solium progesterone receptor (TsPR, since RU486 inhibits both scolex evagination and worm development induced by progesterone. Using RT-PCR and western blot, sequences related to progesterone receptor were detected in the parasite. A phylogenetic analysis reveals that TsPR is highly related to fish and amphibian progesterone receptors, whereas it has a distant relation with birds and mammals. Conclusively, progesterone directly acts upon T. solium cysticerci, possibly through its binding to a progesterone receptor synthesized by the parasite.

  9. Consequences of loss of progesterone receptor expression in development of invasive endometrial cancer

    OpenAIRE

    Hanekamp, Eline; Blok, Leen; Gielen, Susanne; Smid-Koopman, Ellen; Kühne, Liesbeth; Ruiter, Petra; Chadha-Ajwani, Savi; Brinkmann, Albert; Grootegoed, Anton; Burger, Curt; Huikeshoven, Frans

    2003-01-01

    textabstractPURPOSE: In endometrial cancer, loss of progesterone receptors (PR) is associated with more advanced disease. This study aimed to investigate the mechanism of action of progesterone and the loss of its receptors (PRA and PRB) in development of endometrial cancer. EXPERIMENTAL DESIGN: A 9600-cDNA microarray analysis was performed to study regulation of gene expression in the human endometrial cancer subcell line Ishikawa PRAB-36 by the progestagen medroxy progesterone acetate (MPA)...

  10. An electrochemical immunosensor for detecting progesterone in milk from dairy cows

    OpenAIRE

    Wu, Ling; Yang, Wei; Xia, Cheng; Xu, Chuang; Zhang, Hongyou

    2018-01-01

    In this study, an electrochemical immunosensor for milk progesterone produced by dairy cows was developed. Using the immunosensor, milk progesterone levels in healthy estrus dairy cows was found to range from 1 to 6 ng/mL 20 days after estrus. There were high levels of progesterone in the milk from cows with prolonged luteal phase and luteal cysts, which ranged from 15 to 28 and 19 to 29 ng/mL, respectively. Cows with inactive ovaries also showed low milk progesterone levels of 1-8 ng/mL, but...

  11. Progesterone modulates the proliferation and differentiation of human periodontal ligament cells.

    Science.gov (United States)

    Yuan, Gongjie; Cai, Chuan; Dai, Juan; Liu, Yali; Zhang, Rui; Dai, Yuanyuan; Wen, Li; Ding, Yin

    2010-08-01

    Hormone deficiency has been recognized as a risk factor for periodontal disease in postmenopausal women. However, the anabolic effects of progesterone on human periodontal ligament cells (hPDLCs) are still unclear. Therefore, the objective of this study was to detect the expression of progesterone receptor (PgR) in hPDLCs and investigate the bone-sparing effects of progesterone. We detected PgR expression in hPDLCs by reverse transcriptase-polymerase chain reaction and immunocytochemistry. After progesterone stimulation, the percentage of hPDLCs entering the S + G2M phase of the cell cycle increased significantly, accompanied by an increased cell growth curve. In both basic culture medium and osteogenic medium, progesterone activated alkaline phosphatase-positive cells and alizarin red-positive nodules. Moreover, mineralization-related markers were up-regulated by progesterone in both time-dependent and dose-dependent manners. In contrast, these effects of progesterone were blocked by the PgR antagonist (RU486). Our results demonstrated that the PgR is expressed in hPDLCs at the gene and protein level, and that progesterone can stimulate the proliferation and differentiation of the hPDLCs. These findings suggest that progesterone may play a significant role in osteoblastic function of hPDLCs and may influence the maintenance of alveolar bone mass.

  12. Estrogen and progesterone receptors in human breast cancer. Correlation with histologic subtype and degree of differentiation

    National Research Council Canada - National Science Library

    Mohammed, R H; Lakatua, D J; Haus, E; Yasmineh, W J

    1986-01-01

    Microscopic review of 490 consecutive human breast biopsy and mastectomy specimens were correlated with estrogen and progesterone receptor content of the tissue, by subtype and degree of differentiation...

  13. Progesterone increases dopamine neurone number in differentiating mouse embryonic stem cells.

    Science.gov (United States)

    Díaz, N F; Díaz-Martínez, N E; Velasco, I; Camacho-Arroyo, I

    2009-08-01

    Progesterone participates in the regulation of several functions in mammals, including brain differentiation and dopaminergic transmission, but the role of progesterone in dopaminergic cell differentiation is unknown. We investigated the effects of progesterone on dopaminergic differentiation of embryonic stem cells using a five-stage protocol. Cells were incubated with different progesterone concentrations during the proliferation (stage 4) or differentiation (stage 5) phases. Progesterone added at 1, 10 and 100 nm during stage 4 increased the number of dopamine neurones at stage 5 by 72%, 80% and 62%, respectively, compared to the control group. The administration of progesterone at stage 5 did not induce significant changes in the number of dopamine neurones. These actions were not mediated by the activation of intracellular progesterone receptors because RU 486 did not block the positive effects of progesterone on differentiation to dopaminergic neurones. The results obtained suggest that progesterone should prove useful with respect to producing higher proportions of dopamine neurones from embryonic stem cells in the treatment of Parkinson's disease.

  14. Short communication: Plasma progesterone concentration and ovarian dynamics of lactating Jersey cows treated with 1 or 2 intravaginal progesterone inserts.

    Science.gov (United States)

    Moraes, João G N; Silva, Paula R B; Bortoletto, Nathália; Scanavez, Alexandre L A; Chebel, Ricardo C

    2016-03-01

    The objectives of the current experiment were to determine circulating progesterone concentrations and ovarian follicle development of lactating Jersey cows treated with 1 or 2 controlled internal drug release (CIDR) insert containing 1.38 g of progesterone during proestrus. Cows were enrolled in the experiment at 34 ± 3 d in milk and were paired by parity, body condition score, body weight, and milk yield. Estrous cycles were presynchronized with an injection of GnRH concurrent with a new CIDR insert (study d -7) and 2 injections of PGF2α given 5 and 6 d after the GnRH injection (study d -2 and -1, respectively). Cows assigned to the 1CIDR treatment (n=30) or 2CIDR treatment (n=30) received 1 and 2 CIDR inserts, respectively, from study d 0 through 7. Control cows (n=10) did not receive further treatment. On study d -2 and daily from study d 0 through 7, ovaries were examined by transrectal ultrasound and blood samples were collected for determination of progesterone. On study d 7, CIDR inserts were removed after ultrasound exam and blood sample collection. Progesterone concentration from study d 0 through 7 was greatest for 2CIDR cows (2.17 ± 0.09 ng/mL), followed by 1CIDR cows (1.37 ± 0.10 ng/mL) and control cows (0.62 ± 0.21 ng/mL). The interaction between treatment and study day affected progesterone concentration from study d 0 through 7. The average increase in progesterone concentration from study d 1 through 7 was 0.80 ng/mL for 1CIDR and 1.72 ng/mL for 2CIDR cows compared with control cows. The percentage of cows that ovulated between study d 0 and 7 was greatest for control cows (80%), but it did not differ between 1CIDR (12%) and 2CIDR (3.7%) cows. Growth of class III follicles (10-17 mm) identified on study d 0 was affected by treatment because 1CIDR cows had larger class III follicles than 2CIDR cows on study d 5, 6 and 7. A larger proportion of control cows developed a new follicular wave between study d 0 and 7 (control=60.0%, 1CIDR=12.0%, 2

  15. The Role of Progesterone and a Novel Progesterone Receptor, Progesterone Receptor Membrane Component 1, in the Inflammatory Response of Fetal Membranes to Ureaplasma parvum Infection.

    Directory of Open Access Journals (Sweden)

    Liping Feng

    Full Text Available Ureaplasma parvum (U. parvum is gaining recognition as an important pathogen for chorioamnionitis and preterm premature rupture of membranes. We aimed to investigate the roles of progesterone (P4 and a novel progesterone receptor, progesterone receptor membrane component 1 (PGRMC1, in the response of fetal membranes to U. parvum. Fetal membrane cells (amnion, chorion and decidua were isolated and confirmed to be free of Mycoplasmataceae. Cells were treated with U. parvum (5x106 CFU, and adherence was quantified by qPCR. Amnion and chorion cells were transfected with scrambled siRNA or validated PGRMC1 siRNA for 72h. Cells were then treated with U. parvum for 4h with or without pretreatment with P4 (10-7 M or ethanol for 1h. Interleukin-8 (IL-8, matrix metalloproteinase 9 (MMP9 and cyclooxygenase (COX-2 mRNA expression were quantified by qRT-PCR. Culture medium was harvested and analyzed for IL-8 and prostaglandin (PGE2 secretion by ELISA and MMP9 activity by zymography. U. parvum had a mean adherence of 15.0±0.6%, 16.9± 3.7% and 4.7±0.3% in cultured amnion, chorion and decidua cells, respectively. Exposure to U. parvum elicited significant inflammatory responses including induction of IL-8, COX-2, PGE2 and MMP9. A possible role of PGRMC1 was identified in the inhibition of U. parvum-stimulated COX-2 and MMP9 mRNA expression in chorion cells and MMP9 activity in amnion cells. On the other hand, it might enhance the U. parvum-stimulated IL-8 protein secretion in amnion cells. P4, mediated through PGRMC1, significantly inhibited U. Parvum-induced MMP9 mRNA and COX-2 mRNA expression in chorion cells. P4 appeared to attenuate U. parvum induced IL-8 mRNA expression in chorion cells, but this P4 effect might not mediated through PGRMC1. In summary, U. parvum preferentially adheres to and induces inflammatory responses in chorion and amnion cells. P4 and PGRMC1 appear to differentially modulate the inflammatory responses induced by U. parvum among

  16. Dgroup: DG01666 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available DG01666 DGroup Progesterone receptor agonist ... DG00456 ... Norethisterone ... D00182 ... No...N) ... D08285 ... Norethisterone enantate DG00457 ... Megestrol ... D08167 ... Megestrol (INN) ... D00952 ... Megestrol acetat...e (USAN) ... DG00458 ... Medroxyprogesterone ... D08166 ... Medroxyprogesterone (INN) ... D00951 ... Medroxyprogest...erone acetate (JP17/USP) ... DG00467 ... Hydroxyprogesterone ... D08052 ... Hydroxyprogesterone (INN) ... D00949 ... Hydroxyprogest...erone caproate (JAN/USP/INN) ... D08053 ... Hydroxyprogesterone 17alfa-acetate DG00468 ... Nomegest

  17. Progesterone and non-specific immunologic mechanisms in pregnancy.

    Science.gov (United States)

    Szekeres-Bartho, J; Par, G; Szereday, L; Smart, C Y; Achatz, I

    1997-09-01

    Progesterone-dependent immunomodulation is one of the mechanisms that enables pregnancy to proceed to term. Immunologic effects of progesterone are mediated by a protein named the progesterone-induced blocking factor (PIBF). Among other effects this protein inhibits natural killer (NK) activity and displays an anti-abortive effect in mice. Recently, we have shown that PIBF induces a Th2 shift in vitro. The present study was aimed at investigating the in vivo effect of PIBF on cytokine production, as well as the relationship between cytokine production, NK activity, and pregnancy loss. Balb-c mice on day 8.5 of pregnancy were injected intraperitoneally with 0.5 mg of rabbit anti-PIBF immunoglobulin G (IgG). Another group of mice was simultaneously treated with anti-NK monoclonal antibodies. Mice treated with the same amount of normal rabbit serum or untreated mice of similar gestational age were used as controls. The animals were sacrificed and their uteri were inspected. The ratio of living and resorbed embryos was determined. NK activity as well as cytokine expression on the spleen cells were determined by immunocytochemistry and enzyme-linked immunoadsorbent assay (ELISA). Mitogen-activated spleen cells from anti-PIBF-treated mice produced significantly (P < 0.001) less IL-10 than those of pregnant control mice. A significantly higher percentage (P < 0.001) of spleen cells from anti-PIBF-treated mice expressed interferon-gamma (IFN gamma) as determined by immunocytochemistry, than those of untreated pregnant mice. There was a positive relationship between the percentage of IFN gamma-positive spleen cells and resorption rates, and an inverse relationship between the latter and interleukin-10 (IL-10) production. All these effects were corrected by treatment with anti-NK antibodies. Our data suggest that PIBF contributes to the success of gestation via cytokine-mediated inhibition of NK activity.

  18. Prenatal Exposure to Progesterone Affects Sexual Orientation in Humans

    DEFF Research Database (Denmark)

    Reinisch, June M.; Mortensen, Erik Lykke; Sanders, Stephanie A.

    2017-01-01

    Prenatal sex hormone levels affect physical and behavioral sexual differentiation in animals and humans. Although prenatal hormones are theorized to influence sexual orientation in humans, evidence is sparse. Sexual orientation variables for 34 prenatally progesterone-exposed subjects (17 males...... preparation. Controls were matched on 14 physical, medical, and socioeconomic variables. A structured interview conducted by a psychologist and self-administered questionnaires were used to collect data on sexual orientation, self-identification, attraction to the same and other sex, and history of sexual...... in the development of sexual orientation....

  19. Luteal Support for IVF/ICSI Cycles with Crinone 8% (90 mg Twice Daily Results in Higher Pregnancy Rates Than with Intramuscular Progesterone

    Directory of Open Access Journals (Sweden)

    Chi-Hong Ho

    2008-08-01

    Conclusion: The use of vaginal progesterone gel twice daily for luteal support results in better pregnancy outcomes than intramuscular progesterone. A high local progesterone effect from vaginal gel might improve endometrial receptivity under extraordinarily high serum estradiol levels.

  20. Effects of metformin treatment on luteal phase progesterone concentration in polycystic ovary syndrome

    Directory of Open Access Journals (Sweden)

    Meenakumari K.J.

    2004-01-01

    Full Text Available The causes of luteal phase progesterone deficiency in polycystic ovary syndrome (PCOS are not known. To determine the possible involvement of hyperinsulinemia in luteal phase progesterone deficiency in women with PCOS, we examined the relationship between progesterone, luteinizing hormone (LH and insulin during the luteal phase and studied the effect of metformin on luteal progesterone levels in PCOS. Patients with PCOS (19 women aged 18-35 years were treated with metformin (500 mg three times daily for 4 weeks prior to the test cycle and throughout the study period, and submitted to ovulation induction with clomiphene citrate. Blood samples were collected from control (N = 5, same age range as PCOS women and PCOS women during the late follicular (one sample and luteal (3 samples phases and LH, insulin and progesterone concentrations were determined. Results were analyzed by one-way analysis of variance (ANOVA, Duncan's test and Karl Pearson's coefficient of correlation (r. The endocrine study showed low progesterone level (4.9 ng/ml during luteal phase in the PCOS women as compared with control (21.6 ng/ml. A significant negative correlation was observed between insulin and progesterone (r = -0.60; P < 0.01 and between progesterone and LH (r = -0.56; P < 0.05 concentrations, and a positive correlation (r = 0.83; P < 0.001 was observed between LH and insulin. The study further demonstrated a significant enhancement in luteal progesterone concentration (16.97 ng/ml in PCOS women treated with metformin. The results suggest that hyperinsulinemia/insulin resistance may be responsible for low progesterone levels during the luteal phase in PCOS. The luteal progesterone level may be enhanced in PCOS by decreasing insulin secretion with metformin.

  1. Vaginal cytology, vaginoscopy and progesterone profile: breeding tools in bitches

    Directory of Open Access Journals (Sweden)

    K. C. S. Reddy

    2011-01-01

    Full Text Available The exfoliative vaginal cytology, vaginoscopic examination of vaginal mucosa and progesterone profiles were recorded in an attempt to identify the ideal time of breeding in bitches. A total of 18 anestrus bitches were selected and divided into 03 groups (Control, CABG and eCG groups. The bitches in control group did not receive any treatment and exhibited estrus. The estrus was induced with Cabergoline (CABG and equine Chorionic Gonadotropin (eCG in the other two groups of bitches. In control group, higher percentage of superficial cells (89.94 ± 0.64 and lower percentage of intermediate (7.30 ± 0.77 and parabasal cells (2.76 ± 0.30 were characteristic vaginal cytological changes during estrus. Vaginoscopic examination of CABG group of bitches revealed that the vaginal mucus was creamy and paper white with angular shrinkage during estrus. In eCG group of bitches, the plasma progesterone concentration was 1.55 ± 0.19 ng/ml on day 8.00 ± 0.71 of proestrus. The conception rates were 66.66, 83.33 and 83.33 per cent in Control, Cabergoline and eCG groups, respectively. The litter size varied from 3.50 + 1.12 to 4.83 + 0.83 in the three groups.

  2. Progesterone receptor modulates ERα action in breast cancer.

    Science.gov (United States)

    Mohammed, Hisham; Russell, I Alasdair; Stark, Rory; Rueda, Oscar M; Hickey, Theresa E; Tarulli, Gerard A; Serandour, Aurelien A; Serandour, Aurelien A A; Birrell, Stephen N; Bruna, Alejandra; Saadi, Amel; Menon, Suraj; Hadfield, James; Pugh, Michelle; Raj, Ganesh V; Brown, Gordon D; D'Santos, Clive; Robinson, Jessica L L; Silva, Grace; Launchbury, Rosalind; Perou, Charles M; Stingl, John; Caldas, Carlos; Tilley, Wayne D; Carroll, Jason S

    2015-07-16

    Progesterone receptor (PR) expression is used as a biomarker of oestrogen receptor-α (ERα) function and breast cancer prognosis. Here we show that PR is not merely an ERα-induced gene target, but is also an ERα-associated protein that modulates its behaviour. In the presence of agonist ligands, PR associates with ERα to direct ERα chromatin binding events within breast cancer cells, resulting in a unique gene expression programme that is associated with good clinical outcome. Progesterone inhibited oestrogen-mediated growth of ERα(+) cell line xenografts and primary ERα(+) breast tumour explants, and had increased anti-proliferative effects when coupled with an ERα antagonist. Copy number loss of PGR, the gene coding for PR, is a common feature in ERα(+) breast cancers, explaining lower PR levels in a subset of cases. Our findings indicate that PR functions as a molecular rheostat to control ERα chromatin binding and transcriptional activity, which has important implications for prognosis and therapeutic interventions.

  3. Progesterone and Bone: Actions Promoting Bone Health in Women

    Directory of Open Access Journals (Sweden)

    Vanadin Seifert-Klauss

    2010-01-01

    Full Text Available Estradiol (E2 and progesterone (P4 collaborate within bone remodelling on resorption (E2 and formation (P4. We integrate evidence that P4 may prevent and, with antiresorptives, treat women's osteoporosis. P4 stimulates osteoblast differentiation in vitro. Menarche (E2 and onset of ovulation (P4 both contribute to peak BMD. Meta-analysis of 5 studies confirms that regularly cycling premenopausal women lose bone mineral density (BMD related to subclinical ovulatory disturbances (SODs. Cyclic progestin prevents bone loss in healthy premenopausal women with amenorrhea or SOD. BMD loss is more rapid in perimenopause than postmenopause—decreased bone formation due to P4 deficiency contributes. In 4 placebo-controlled RCTs, BMD loss is not prevented by P4 in postmenopausal women with increased bone turnover. However, 5 studies of E2-MPA co-therapy show greater BMD increases versus E2 alone. P4 fracture data are lacking. P4 prevents bone loss in pre- and possibly perimenopausal women; progesterone co-therapy with antiresorptives may increase bone formation and BMD.

  4. Novel Progesterone Receptors: Neural Localization and Possible Functions

    Directory of Open Access Journals (Sweden)

    Sandra L Petersen

    2013-09-01

    Full Text Available Progesterone (P4 regulates a wide range of neural functions and likely acts through multiple receptors. Over the past 30 years, most studies investigating neural effects of P4 focused on genomic and non-genomic actions of the classical progestin receptor (PGR. More recently the focus has widened to include two groups of non-classical P4 signaling molecules. Members of the Class II progestin and adipoQ receptor (PAQR family are called membrane progestin receptors (mPRs and include: mPRα (PAQR7, mPRβ (PAQR8, mPRγ (PAQR5, mPRδ (PAQR6 and mPRε (PAQR9. Members of the b5-like heme/steroid-binding protein family include progesterone receptor membrane component 1 (PGRMC1, PGRMC2, neudesin and neuferricin. Results of our recent mapping studies show that members of the PGRMC1/S2R family, but not mPRs, are quite abundant in forebrain structures important for neuroendocrine regulation and other non-genomic effects of P4. Herein we describe the structures, neuroanatomical localization and signaling mechanisms of these molecules. We also discuss possible roles for Pgrmc1/S2R in gonadotropin release, feminine sexual behaviors, fluid balance and neuroprotection, as well as catamenial epilepsy.

  5. Progesterone Inhibits Human Myometrial Contractions by Action on Membrane Receptors

    Directory of Open Access Journals (Sweden)

    Remzi Gokdeniz

    2013-02-01

    Full Text Available Background: The mechanisms for myometrial inhibition are still being investigated Aim: To examine mechanisms of progesterone (P4 inhibition of uterine contractility. Methods: Prospective study Tertiary care center at St. Joseph’s Hospital and at Maricopa Hospital, Phoenix, AZ and research center in Arizona, USA. During 2010-2011, 24 women given birth by cesarean section. Uterine tissues from women (n=24 at term were suspended in organ chambers and exposed to various agents. Contractility was registered and compared before and after addition of agents. Tissues were treated with P4 alone, a progestin (R5020 with low affinity to the progesterone membrane receptor (mPR, or a non-sex steroid (cholesterol. Other tissues were pretreated with inhibitors of adenylate cyclase (SQ 22536, phosphodiesterase (rolipram, nitric oxide (NO synthases (L-NAME or a nuclear P4 receptor antagonist (mifepristone, MIF, followed by P4. Data were analyzed by ANOVA. Results: P4 (P0.05 inhibitory effects. P4 inhibition is not blocked by MIF, SQ, ODQ, rolipram or L-NAME (P>0.05. Conclusions: P4 rapidly inhibits myometrial contractility by nongenomic mechanisms through action on mPR but not via cAMP, cGMP, or NO [Cukurova Med J 2013; 38(1.000: 92-102

  6. Stress-induced increases in progesterone and cortisol in naturally cycling women

    Directory of Open Access Journals (Sweden)

    Alexandra Ycaza Herrera

    2016-06-01

    Full Text Available Studies with animals of both sexes show that the adrenal glands release progesterone in addition to cortisol in response to stress. However, little is known about the progesterone response to stress in naturally cycling women. We investigated the effect of stress on estradiol, progesterone, and cortisol levels in women during the follicular phase of the menstrual cycle. We found that physical stress (the cold pressor test had no effect on estradiol levels, but increased progesterone and cortisol. We also found positive correlations between baseline progesterone and cortisol levels, as well as between the change in progesterone and cortisol before and after water exposure in both the stress and control sessions. Mediation analyses revealed during the stress session, the change in progesterone from baseline to 42-min post-stress onset was mediated by the magnitude of change in cortisol levels across the same time span. Overall, these findings reveal that progesterone released in response to stress as observed in animals and men extends to women during the low ovarian output follicular phase of the menstrual cycle, and that the mechanism of release may be similar to the mechanism of cortisol release.

  7. Estrogen and progesterone receptors in human breast cancer. Correlation with histologic subtype and degree of differentiation.

    Science.gov (United States)

    Mohammed, R H; Lakatua, D J; Haus, E; Yasmineh, W J

    1986-09-01

    Microscopic review of 490 consecutive human breast biopsy and mastectomy specimens were correlated with estrogen and progesterone receptor content of the tissue, by subtype and degree of differentiation. Of the 4 grades of differentiation, the less differentiated Grade III and IV tumors showed significantly lower levels of estrogen and progesterone receptors in infiltrating ductal and lobular carcinoma (P less than 0.001). In contrast, patients with medullary carcinoma had the lowest tissue levels of estrogen and progesterone receptors with approximately 80% of the cases with less than 10 fmol/mg protein. Patients with mucinous carcinoma had the highest percentages of positive estrogen and progesterone receptor levels (75% and 87%, respectively). Sixty-three percent of the patients with Grade IV infiltrating ductal carcinoma were younger than 53 years of age (P less than 0.001). Patients younger than 53 years of age with Grade II and III infiltrating ductal carcinoma also had significantly lower levels of estrogen receptors, but not of progesterone receptors, than those patients older than 53 years of age (P less than 0.001). Nineteen of 20 "normal" breast tissue specimens were negative (less than 3 fmol/mg protein) for estrogen and progesterone receptors. About 50% of 17 tissue specimens from benign breast lesions (fibroadenoma, fibrocystic disease, sclerosing adenosis) showed positive estrogen (greater than 10 fmol/mg protein) or progesterone receptor values. In two patients with gynecomastia, no estrogen or progesterone receptors were detectable.

  8. Progesterone-induced spike-wave discharges are inhibited by finasteride

    NARCIS (Netherlands)

    Budziszewska, B.; Tetich, M.; Luijtelaar, E.L.J.M. van; Lason, W.

    2004-01-01

    Previously, it was found that progesterone aggravates spike-wave discharges (SWD) in WAG/Rij rats in a non-genomic way. In order to elucidate whether the regulatory effect of progesterone depends on its conversion to allopregnanolone, the effect of finasteride, a 5?-reductase inhibitor, on

  9. Development of a competitive lateral flow immunoassay for progesterone : influence of coating conjugates and buffer components

    NARCIS (Netherlands)

    Posthuma-Trumpie, Geertruida A.; Korf, Jakob; van Amerongen, Aart

    2008-01-01

    Several aspects of the development of competitive lateral flow immunoassays (LFIAs) are described. The quantitation of progesterone is taken as an example. The LFIA format consisted of a nitrocellulose membrane spotted with various progesterone conjugates as the test line. A mixture of primary

  10. Development of a competitive lateral flow immunoassay for progesterone: influence of coating conjugates and buffer components

    NARCIS (Netherlands)

    Posthuma-Trumpie, G.A.; Korf, J.; Amerongen, van A.

    2008-01-01

    Several aspects of the development of competitive lateral flow immunoassays (LFIAs) are described. The quantitation of progesterone is taken as an example. The LFIA format consisted of a nitrocellulose membrane spotted with various progesterone conjugates as the test line. A mixture of primary

  11. Serum progesterone as an indicator of cyclic activity in post-partum ...

    African Journals Online (AJOL)

    user

    Serum progesterone as an indicator of cyclic activity in post-partum goat does. V.M. Mmbengwa ... Reproduction is a major factor contributing to the efficiency of meat and milk production (Khanum et al.,. 2008). .... where energy intake was limited, exhibited low levels of serum progesterone concentrations and consequently.

  12. Progesterone receptor structure and protease activity in primary human endometrial carcinoma.

    Science.gov (United States)

    Feil, P D; Clarke, C L; Satyaswaroop, P G

    1988-03-01

    Monoclonal antibodies were used to investigate progesterone receptor structure (isoforms) in 33 primary human endometrial tumors. The monoclonal antibodies recognized on protein blots two progesterone receptor proteins with molecular weights of 116,000 and 81,000. The Mr 116,000 protein appeared as a triplet, while a single band was found for the Mr 81,000 protein. The triplet/singlet structure was found in all progesterone receptor-positive tumors, regardless of the degree of tumor differentiation. Protease activity, which gave rise to a false-negative pattern on protein blots, was found in approximately one-half of the tumors in which it was investigated. Inclusion of a cocktail of protease inhibitors during sample preparation resulted in the maintenance of the triplet/singlet progesterone receptor structure. Mixing experiments using a progesterone receptor-rich human endometrial carcinoma (EnCa 101), which lacks protease activity, and protease-containing primary tumor homogenates indicated that the protease was leupeptin sensitive. Interestingly, while the proteolytic activity reduced or eliminated the triplet/singlet progesterone receptor structure seen on protein blot analysis, it did not affect progesterone receptor concentration measured by Scatchard analysis. Sample preparation in the presence of protease inhibitors is therefore a requisite for structural analysis of the progesterone receptor in endometrial tumors.

  13. Radioimmunoassays to determine the presence of progesterone and estrone in the starfish Asterias rubens

    NARCIS (Netherlands)

    Dieleman, S.J.; Schoenmakers, H.J.N.

    1979-01-01

    RIA's have been made for progesterone and estrone with the antisera S74B7 and 7604-7 40, respectively, which will be described. The characteristics of the RIA for progesterone resemble those of other reported RIA's. The antiserum for the RIA of estrone is highly specific, with main cross-reactions

  14. Influence of the reuse of progesterone implants in a fixed-time ...

    African Journals Online (AJOL)

    aghomotsegin

    2015-01-28

    Jan 28, 2015 ... the reuse of the P4 implant can influence the conception rates of dairy cows. Key words: Heat stress, Holstein cows, ... progesterone concentration achieved after insertion of new or reused progesterone ... insemination was performed with semen from the same bull and single inseminator. A pregnancy ...

  15. Oral progesterone decreases saccadic eye velocity and increases sedation in women.

    NARCIS (Netherlands)

    Broekhoven, F. van; Backstrom, T.; Verkes, R.J.

    2006-01-01

    The aim of this study was to investigate the neurophysiological and behavioural effects of a single dose of progesterone in women. Allopregnanolone is a metabolite of progesterone and a potent positive modulator of the GABA(A) receptor and produces sedative and anxiolytic effects. This study was

  16. Progesterone treatment shows greater protection in brain vs. retina in a rat model of middle cerebral artery occlusion: Progesterone receptor levels may play an important role.

    Science.gov (United States)

    Allen, Rachael S; Sayeed, Iqbal; Oumarbaeva, Yuliya; Morrison, Katherine C; Choi, Paul H; Pardue, Machelle T; Stein, Donald G

    2016-11-22

    To determine whether inflammation increases in retina as it does in brain following middle cerebral artery occlusion (MCAO), and whether the neurosteroid progesterone, shown to have protective effects in both retina and brain after MCAO, reduces inflammation in retina as well as brain. MCAO rats treated systemically with progesterone or vehicle were compared with shams. Protein levels of cytosolic NF-κB, nuclear NF-κB, phosphorylated NF-κB, IL-6, TNF-α, CD11b, progesterone receptor A and B, and pregnane X receptor were assessed in retinas and brains at 24 and 48 h using western blots. Following MCAO, significant increases were observed in the following inflammatory markers: pNF-κB and CD11b at 24 h in both brain and retina, nuclear NF-κB at 24 h in brain and 48 h in retina, and TNF-α at 24 h in brain.Progesterone treatment in MCAO animals significantly attenuated levels of the following markers in brain: pNF-κB, nuclear NF-κB, IL-6, TNF-α, and CD11b, with significantly increased levels of cytosolic NF-κB. Retinas from progesterone-treated animals showed significantly reduced levels of nuclear NF-κB and IL-6 and increased levels of cytosolic NF-κB, with a trend for reduction in other markers. Post-MCAO, progesterone receptors A and B were upregulated in brain and downregulated in retina. Inflammatory markers increased in both brain and retina after MCAO, with greater increases observed in brain. Progesterone treatment reduced inflammation, with more dramatic reductions observed in brain than retina. This differential effect may be due to differences in the response of progesterone receptors in brain and retina after injury.

  17. Effects of dexamethasone on progesterone and estrogen profiles and uterine progesterone receptor localization during pregnancy in Sahel goat in Semi-Arid region

    Directory of Open Access Journals (Sweden)

    Dauda Yahi

    2017-05-01

    Full Text Available Abstract Background Despite the widespread use of dexamethasone in veterinary and human medicine, it is reported to cause some severe pregnancy related side effects like abortion in some animals. The mechanism of the response is not clear but seems to be related to interspecies and/or breed difference in response which may involve alterations in the concentrations of some reproductive hormones. Methods Twenty Sahel goats comprising 18 does and 2 bucks were used for this study. Pregnancies were achieved by natural mating after synchronization. Repeated dexamethasone injections were given at 0.25 mg/kg body weight. Blood samples were collected biweekly for hormonal assay. Uterine biopsies were harvested at days 28 and day 78 of gestation through caesarean section for immunohistochemical analysis using 3 pregnant does randomly selected from each group at each instant. Data were expressed as Means ± Standard Deviations and analyzed using statistical soft ware package, GraphPad Instant, version 3.0 (2003 and progesterone receptor (PR were scored semi-quantitatively. Results Dexamethasone treatments had no significant (p > 0.05 effect on progesterone and estrogen concentrations in pregnant Sahel goats but up regulated PR from 2+ to 3+ in second trimester. Conclusion As dexamethasone adverse effect on placenta is an established fact, the lack of effect on progesterone level in this study may be due to the fact that unlike other species whose progesterone production during pregnancy is placenta – dependent, in goats is corpus luteum - dependent. Consequently dexamethasone adverse effect on placenta reported in literatures did not influence progesterone levels during pregnancy in Sahel goat. The up regulation of progesterone receptor (PR in Sahel goat gravid uterus is a beneficial effects and that dexamethasone can safely be used in corpus luteum – dependent progesterone secreting pregnant animal species like Sahel goat and camel. Therefore

  18. Effects of dexamethasone on progesterone and estrogen profiles and uterine progesterone receptor localization during pregnancy in Sahel goat in Semi-Arid region.

    Science.gov (United States)

    Yahi, Dauda; Ojo, Nicholas Adetayo; Mshelia, Gideon Dauda

    2017-01-01

    Despite the widespread use of dexamethasone in veterinary and human medicine, it is reported to cause some severe pregnancy related side effects like abortion in some animals. The mechanism of the response is not clear but seems to be related to interspecies and/or breed difference in response which may involve alterations in the concentrations of some reproductive hormones. Twenty Sahel goats comprising 18 does and 2 bucks were used for this study. Pregnancies were achieved by natural mating after synchronization. Repeated dexamethasone injections were given at 0.25 mg/kg body weight. Blood samples were collected biweekly for hormonal assay. Uterine biopsies were harvested at days 28 and day 78 of gestation through caesarean section for immunohistochemical analysis using 3 pregnant does randomly selected from each group at each instant. Data were expressed as Means ± Standard Deviations and analyzed using statistical soft ware package, GraphPad Instant, version 3.0 (2003) and progesterone receptor (PR) were scored semi-quantitatively. Dexamethasone treatments had no significant (p > 0.05) effect on progesterone and estrogen concentrations in pregnant Sahel goats but up regulated PR from 2+ to 3+ in second trimester. As dexamethasone adverse effect on placenta is an established fact, the lack of effect on progesterone level in this study may be due to the fact that unlike other species whose progesterone production during pregnancy is placenta - dependent, in goats is corpus luteum - dependent. Consequently dexamethasone adverse effect on placenta reported in literatures did not influence progesterone levels during pregnancy in Sahel goat. The up regulation of progesterone receptor (PR) in Sahel goat gravid uterus is a beneficial effects and that dexamethasone can safely be used in corpus luteum - dependent progesterone secreting pregnant animal species like Sahel goat and camel. Therefore source of progesterone secretions during pregnancy should be considered

  19. Vaginal versus intramuscular progesterone in the prevention of preterm labor and their effect on uterine and fetal blood flow

    Directory of Open Access Journals (Sweden)

    Azza A. Abd El Hameed

    2012-09-01

    Conclusion: Vaginally administrated progesterone was nearly as equally effective as intra muscular progesterone in the prevention of PTL in women at risk and both were associated with significant reduction in fetal MCA-PI and RI, but a significant reduction in uterine artery RI and PI was observed only after vaginal progesterone.

  20. Comparison of the administration of progesterone versus progesterone and vitamin D in improvement of outcomes in patients with traumatic brain injury: A randomized clinical trial with placebo group.

    Science.gov (United States)

    Aminmansour, Bahram; Nikbakht, Hossein; Ghorbani, Abbas; Rezvani, Majid; Rahmani, Paiman; Torkashvand, Mostaffa; Nourian, Mohammadamin; Moradi, Mehran

    2012-01-01

    Due to the heterogeneity of traumatic brain injury (TBI), many of single treatments have not been successful in prevention and cure of these kinds of injuries. The neuroprotective effect of progesterone drug on severe brain injuries has been identified, and recently, the neuroprotective effect of vitamin D has also been studied as the combination of these two drugs has shown better effects on animal samples in some studies. This study was conducted to examine the effect of vitamin D and progesterone on brain injury treatment after brain trauma. This study was performed on patients with severe brain trauma (Glasgow Coma Scale (GCS) ≤ 8) from April to September, 2011. The patients were divided to 3 groups (placebo, progesterone, progesterone-vitamin D), each with 20 people. Upon the patients' admission, their GCS and demographic information were recorded. After 3 months, they were reassessed, and their GCS and GOS (Glasgow outcome scale) were recorded. The collected data were analyzed using SPSS 18 software (SPSS Inc., Chicago IL, USA). Before intervention, GCS mean of the placebo, progesterone, and progesterone-vitamin D groups were 6.3 ± 0.88, 6.31 ± 0.87, and 6 ± 0.88, respectively. They increased to 9.16 ± 1.11, 10.25 ± 1.34, and 11.27 ± 2.27, respectively 3 months after intervention. There was a significant difference among GCS means of the 3 groups (P-value = 0.001). GOS was classified to 2 main categories of favorable and unfavorable recovery, of which, favorable recovery in placebo, progesterone, and progesterone-vitamin D was 25%, 45%, and 60%, respectively which showed a statistical significant difference among the groups (P-value = 0.03). The results showed that recovery rate in patients with severe brain trauma in the group receiving progesterone and vitamin D together was significantly higher than that of progesterone group, which was in turn higher than that of placebo group.

  1. Comparison of the administration of progesterone versus progesterone and vitamin D in improvement of outcomes in patients with traumatic brain injury: A randomized clinical trial with placebo group

    Directory of Open Access Journals (Sweden)

    Bahram Aminmansour

    2012-01-01

    Full Text Available Background: Due to the heterogeneity of traumatic brain injury (TBI, many of single treatments have not been successful in prevention and cure of these kinds of injuries. The neuroprotective effect of progesterone drug on severe brain injuries has been identified, and recently, the neuroprotective effect of vitamin D has also been studied as the combination of these two drugs has shown better effects on animal samples in some studies. This study was conducted to examine the effect of vitamin D and progesterone on brain injury treatment after brain trauma. Materials and Methods: This study was performed on patients with severe brain trauma (Glasgow Coma Scale (GCS ≤ 8 from April to September, 2011. The patients were divided to 3 groups (placebo, progesterone, progesterone-vitamin D, each with 20 people. Upon the patients′ admission, their GCS and demographic information were recorded. After 3 months, they were reassessed, and their GCS and GOS (Glasgow outcome scale were recorded. The collected data were analyzed using SPSS 18 software (SPSS Inc., Chicago IL, USA. Results: Before intervention, GCS mean of the placebo, progesterone, and progesterone-vitamin D groups were 6.3 ± 0.88, 6.31 ± 0.87, and 6 ± 0.88, respectively. They increased to 9.16 ± 1.11, 10.25 ± 1.34, and 11.27 ± 2.27, respectively 3 months after intervention. There was a significant difference among GCS means of the 3 groups (P-value = 0.001. GOS was classified to 2 main categories of favorable and unfavorable recovery, of which, favorable recovery in placebo, progesterone, and progesterone-vitamin D was 25%, 45%, and 60%, respectively which showed a statistical significant difference among the groups (P-value = 0.03. Conclusion: The results showed that recovery rate in patients with severe brain trauma in the group receiving progesterone and vitamin D together was significantly higher than that of progesterone group, which was in turn higher than that of placebo group.

  2. The inactivation of cytochrome P450 3A5 by 17alpha-ethynylestradiol is cytochrome b5-dependent: metabolic activation of the ethynyl moiety leads to the formation of glutathione conjugates, a heme adduct, and covalent binding to the apoprotein.

    Science.gov (United States)

    Lin, Hsia-Lien; Hollenberg, Paul F

    2007-04-01

    17Alpha-ethynylestradiol (EE) inactivates cytochrome P450 3A5 (3A5) in the reconstituted system in a mechanism-based manner. The inactivation is dependent on NADPH, and it is irreversible. The inactivation of 3A5 by EE is also dependent on cytochrome b5 (b5). The values for the K(I) and k(inact) of the 7-benzyloxy-4-(trifluoromethyl)coumarin O-debenzylation activity of 3A5 are 26 microM and 0.06 min(-1), respectively. Incubation of 3A5 with EE resulted in a 62% loss of catalytic activity, 60% loss in the reduced CO difference spectrum, and 40% decrease in native heme with the formation of a heme adduct. The partition ratio was approximately 25, and the stoichiometry of binding was approximately 0.3 mol of EE metabolite bound/mol of P450 inactivated. Four major metabolites were formed during the metabolism of EE by 3A5. SDS-polyacrylamide gel electrophoresis analysis demonstrated that [3H]EE was irreversibly bound to 3A5 apoprotein. Liquid chromatography-tandem mass spectrometry analysis (LC-MS/MS) revealed that two glutathione (GSH) conjugates with m/z values of 620 were formed only in the presence of b5. These two conjugates are formed from the reaction of GSH with the ethynyl group with the oxygen being inserted into either the internal or terminal carbon. A heme adduct with the ion at m/z 927 and two dipyrrole adducts with ions at m/z 579 were detected by LC-MS/MS analysis. In conclusion, 3A5 can activate EE to a 17alpha-oxirene-related reactive species that can then partition the oxygen between the internal and terminal carbons of the ethynyl group to form heme and apoprotein adducts, resulting in the inactivation of P450 3A5.

  3. Ulipristal acetate, a progesterone receptor modulator for emergency contraception

    Science.gov (United States)

    Jadav, Shilpa P.; Parmar, Dinesh M.

    2012-01-01

    Unwanted pregnancy is a global reproductive health problem. Emergency contraception is defined as the use of drug or device after unprotected or underprotected intercourse to prevent an unwanted pregnancy. 1.5 mg of levonorgestrel as a single dose or in two doses with 12 h apart taken within 72 h of unprotected intercourse is the current gold standard emergency contraception regimen. This method is only effective if used as soon as possible after sexual intercourse and before ovulation. A single dose of 30 mg ulipristal acetate, a novel selective progesterone receptor modulator, has recently been proposed for the emergency contraception use up to 120 h of unprotected intercourse with similar side effect profiles as levonorgestrel. Ulipristal acetate could possibly prevent pregnancy when administered in the advanced follicular phase, even if luteinizing hormone levels have already begun to rise, a time when levonorgestrel is no longer effective in inhibiting ovulation. PMID:22629083

  4. Progesterone release from magnetic alginate/chitosan microcapsules

    Energy Technology Data Exchange (ETDEWEB)

    Leite, Melina Vasconcelos; Castro, Mayara de Freitas e; Sanchez Rodriguez, Ruben J., E-mail: sanchez@uenf.br [Universidade Estadual do Norte Fluminense (UENF), Campos dos Goytacazes, RJ (Brazil); Rojas-Ayala, Chachi; Baggio-Saitovitch, Elisa Maria [Centro Brasileiro de Pesquisa Fisicas (CBPF), Rio de Janeir, RJ (Brazil)

    2015-07-01

    Magnetite nanoparticles (Fe{sub 3}O{sub 4}) were prepared using the hydrothermal method (160°C) in a closed system and characterized with the aid of the techniques of X-ray Diffraction patterns (DRX), Mössbauer spectroscopy and Vibrating Sample Magnetometer (VSM). The Fe{sub 3}O{sub 4} phase showed high crystallinity and medium crystallite size of 19nm with superparamagnetic properties, reversible behavior and saturation magnetization of 43 emu g{sup -1}. The nanoparticles coated with alginate / chitosan were characterized morphologically by Scanning and Transmission Electron Microscope. The microcapsules have a regular spherical shape with the main contribution of the size distribution in the range of 34-53μm. The progesterone released was 14% higher when external magnetic field was applied. (author)

  5. Inverse Relationship between Progesterone Receptor and Myc in Endometrial Cancer.

    Directory of Open Access Journals (Sweden)

    Tamar Kavlashvili

    Full Text Available Endometrial cancer, the most common gynecologic malignancy, is a hormonally-regulated disease. Response to progestin therapy positively correlates with hormone receptor expression, in particular progesterone receptor (PR. However, many advanced tumors lose PR expression. We recently reported that the efficacy of progestin therapy can be significantly enhanced by combining progestin with epigenetic modulators, which we term "molecularly enhanced progestin therapy." What remained unclear was the mechanism of action and if estrogen receptor α (ERα, the principle inducer of PR, is necessary to restore functional expression of PR via molecularly enhanced progestin therapy. Therefore, we modeled advanced endometrial tumors that have lost both ERα and PR expression by generating ERα-null endometrial cancer cell lines. CRISPR-Cas9 technology was used to delete ERα at the genomic level. Our data demonstrate that treatment with a histone deacetylase inhibitor (HDACi was sufficient to restore functional PR expression, even in cells devoid of ERα. Our studies also revealed that HDACi treatment results in marked downregulation of the oncogene Myc. We established that PR is a negative transcriptional regulator of Myc in endometrial cancer in the presence or absence of ERα, which is in contrast to studies in breast cancer cells. First, estrogen stimulation augmented PR expression and decreased Myc in endometrial cancer cell lines. Second, progesterone increased PR activity yet blunted Myc mRNA and protein expression. Finally, overexpression of PR by adenoviral transduction in ERα-null endometrial cancer cells significantly decreased expression of Myc and Myc-regulated genes. Analysis of the Cancer Genome Atlas (TCGA database of endometrial tumors identified an inverse correlation between PR and Myc mRNA levels, with a corresponding inverse correlation between PR and Myc downstream transcriptional targets SRD5A1, CDK2 and CCNB1. Together, these data

  6. A critical period of progesterone withdrawal precedes menstruation in macaques

    Science.gov (United States)

    Slayden, Ov D; Brenner, Robert M

    2006-01-01

    Macaques are menstruating nonhuman primates that provide important animal models for studies of hormonal regulation in the uterus. In women and macaques the decline of progesterone (P) at the end of the cycle triggers endometrial expression of a variety of matrix metalloproteinase (MMP) enzymes that participate in tissue breakdown and menstrual sloughing. To determine the minimal duration of P withdrawal required to induce menses, we assessed the effects of adding P back at various time points after P withdrawal on both frank bleeding patterns and endometrial MMP expression. Artificial menstrual cycles were induced by treating the animals sequentially with implants releasing estradiol (E2) and progesterone (P). To assess bleeding patterns, P implants were removed at the end of a cycle and then added back at 12, 24, 30, 36, 40, 48, 60, or 72 hours (h) after the initial P withdrawal. Observational analysis of frank bleeding patterns showed that P replacement at 12 and 24 h blocked menses, replacement at 36 h reduced menses but replacement after 36 h failed to block menses. These data indicate that in macaques, a critical period of P withdrawal exists and lasts approximately 36 h. In other similarly cycled animals, we withdrew P and then added P back either during (12–24 h) or after (48 h) the critical period, removed the uterus 24 h after P add back and evaluated endometrial MMP expression. Immunocytochemistry showed that replacement of P during the critical period suppressed MMP-1, -2 and -3 expression along with menses, but replacement of P at 48 h, which failed to suppress mense, suppressed MMP-1 and MMP-3 but did not block MMP-2. We concluded that upregulation of MMPs is essential to menses induction, but that after the critical period, menses will occur even if some MMPs are experimentally blocked. PMID:17118170

  7. Intestinal tumorigenesis is not affected by progesterone signaling in rodent models.

    Directory of Open Access Journals (Sweden)

    Jarom Heijmans

    Full Text Available Clinical data suggest that progestins have chemopreventive properties in the development of colorectal cancer. We set out to examine a potential protective effect of progestins and progesterone signaling on colon cancer development. In normal and neoplastic intestinal tissue, we found that the progesterone receptor (PR is not expressed. Expression was confined to sporadic mesenchymal cells. To analyze the influence of systemic progesterone receptor signaling, we crossed mice that lacked the progesterone receptor (PRKO to the Apc(Min/+ mouse, a model for spontaneous intestinal polyposis. PRKO-Apc(Min/+ mice exhibited no change in polyp number, size or localization compared to Apc(Min/+. To examine effects of progestins on the intestinal epithelium that are independent of the PR, we treated mice with MPA. We found no effects of either progesterone or MPA on gross intestinal morphology or epithelial proliferation. Also, in rats treated with MPA, injection with the carcinogen azoxymethane did not result in a difference in the number or size of aberrant crypt foci, a surrogate end-point for adenoma development. We conclude that expression of the progesterone receptor is limited to cells in the intestinal mesenchyme. We did not observe any effect of progesterone receptor signaling or of progestin treatment in rodent models of intestinal tumorigenesis.

  8. Effects of estradiol and progesterone on the reproduction of the freshwater crayfish Cherax albidus.

    Science.gov (United States)

    Coccia, E; De Lisa, E; Di Cristo, C; Di Cosmo, A; Paolucci, M

    2010-02-01

    In this study we have investigated the role of 17beta-estradiol and progesterone in the reproduction of the crayfish Cherax albidus by using vitellogenin (VTG) as a biomarker. Early-vitellogenic (EV), full-vitellogenic (FV), and non-vitellogenic (NV) females of Cherax albidus were treated with 17beta-estradiol, progesterone, or both for 4 weeks. Levels of VTG mRNA in the hepatopancreas were detected by RT-PCR. The PCR product was sequenced and showed 97% homology with Cherax quadricarinatus VTG. 17beta-estradiol was more effective than progesterone and 17beta-estradiol plus progesterone in increasing the vitellogenin transcript in the hepatopancreas of EV and FV females. On the contrary, progesterone was more effective than 17beta-estradiol and 17beta-estradiol plus progesterone in increasing the vitellogenin concentration in the hemolymph of EV and FV females. Hepatopancreas histology and fatty acid composition of females injected with hormones showed major modifications. No effects were registered in NV females. In conclusion, 17beta-estradiol and progesterone influence VTG synthesis, although our data indicate that they act through different pathways and are not effective until the proper hormonal environment is established, as demonstrated by their inefficacy in NV females.

  9. Variability of ovarian structures and plasma progesterone profiles in dairy cows with ovarian cysts.

    Science.gov (United States)

    Carroll, D J; Pierson, R A; Hauser, E R; Grummer, R R; Combs, D K

    1990-08-01

    Weekly reproductive health examinations were performed on 46 multiparous Holstein cows from 14 to 100 d post partum. Sixteen cows developed 19 nonsimultaneous ovarian cysts, with a mean day of first detection at 34.3 +/- 4.5 d post partum and a mean duration of 31.0 +/- 4.3 d after first detection. Coccygeal blood was collected three times weekly, and plasma progesterone concentrations were determined by radioimmunoassay. Cysts were diagnosed by palpation per rectum or by ultrasonography and classified as follicular or luteal cysts; the cows were not treated. Cows with a mean plasma progesterone concentration of cyst until Day 10 were classified as having a follicular cyst, and those with a mean plasma progesterone concentration of >or= 1 ng/ml from Day 1 to Day 10 were classified as having a luteal cyst. According to this classification, 58% of the cysts were follicular and 42% were luteal. There was an overall 47% agreement between classification by palpation and by ultrasonography on Day 1 with progesterone concentration during Days 1 to 10 after detection of the cyst. Detailed graphs of progesterone concentrations and area of largest follicles or cysts and corpora lutea demonstrate the variability of ovarian structures and progesterone profiles in cystic cows. Detection of a cyst at any one time accompanied by simultaneous measurement of progesterone can lead to different diagnoses of cyst type depending on the method of classification, the presence and age of luteinized tissue in the cyst and undetected corpora lutea.

  10. Effect of a single injection of progesterone on ovarian follicular cysts in lactating dairy cows.

    Science.gov (United States)

    Hatler, T B; Hayes, S H; Anderson, L H; Silvia, W J

    2006-09-01

    The objective of this experiment was to evaluate the effect of a single injection of progesterone on the lifespan of ovarian follicular cysts and to examine the fate of follicles that mature following treatment. Lactating Holstein and Jersey cows with ovarian follicular cysts were identified by rectal palpation. The ovaries of cystic cows were then examined by transrectal ultrasonography three times weekly to monitor formation of new follicular cysts. Cows with newly formed follicular cysts were treated either with a single injection of progesterone (200 mg, IM, n = 11) or corn oil vehicle (n = 7). Venous blood samples were collected daily for quantification of progesterone. Blood sampling and ultrasonography continued until ovulation or a new follicular cyst formed. Treatment reduced the lifespan of the cyst by 12 days, from 29.8 +/- 2.3 days in control cows to 17.2 +/- 1.8 days in progesterone-treated cows (P = 0.01). Progesterone treatment also tended to alter the frequency of subsequent follicular events. Ovulation occurred in 4/11 cows that were treated with progesterone whereas none of the vehicle treated cows ovulated (P = 0.07). In conclusion, a single injection of 200mg of progesterone, administered early in the life of an ovarian follicular cyst, shortened its lifespan and in some cases was followed by ovulation of a new follicle.

  11. Development of a TIRF-based biosensor for sensitive detection of progesterone in bovine milk.

    Science.gov (United States)

    Käppel, Nina D; Pröll, Florian; Gauglitz, Guenter

    2007-04-15

    A total internal reflectance fluorescence (TIRF)-based biosensor for progesterone in bovine milk was developed and tested by measuring the progesterone level in daily milk samples for 25 days, covering a whole estrus cycle. The detection is based on total internal reflectance fluorescence. The assay has been designed as a binding-inhibition test with a progesterone derivative covalently immobilized on the sensor surface and a monoclonal anti-progesterone antibody as biological recognition element. First an existing progesterone assay was optimized by reducing the assay time per measurement, resulting in an assay time of about 5 min and reaching a limit of detection (LOD) of 0.04 ng mL(-1) and a quantification limit (LOQ) of 0.34 ng mL(-1). After calibration the assay was tested by measuring the progesterone level in daily milk samples over several weeks. An estrus cycle of a cow could be measured. As results become available within minutes without any preparation or pre-concentration of the milk samples the fully automated TIRF-based biosensor for progesterone can be used in-line in the milking parlor and thus could be an important tool for reproductive management of dairy cattle detecting heat and predicting pregnancy, which are critical parameters in milk production.

  12. Inhalation of progesterone inhibits chronic airway inflammation of mice exposed to ozone.

    Science.gov (United States)

    Fei, Xia; Bao, Wuping; Zhang, Pengyu; Zhang, Xue; Zhang, Guoqing; Zhang, Yingying; Zhou, Xin; Zhang, Min

    2017-05-01

    Chronic ozone exposure leads to a model of mice with lung inflammation, emphysema and oxidative stress. Progesterone plays an important role in attenuating the neuroinflammation. We assume that progesterone will reduce the chronic airway inflammation exposed to ozone and evaluate whether combination of progesterone with glucocorticoids results in synergistic effects. C57/BL6 mice were exposed to ozone (2.5ppm, 3h) 12 times over 6 weeks, and were administered with progesterone (0.03 or 0.3mg/L; inhaled) alone or combined with budesonide (BUD) (0.2g/L) after each exposure until the tenth week. Mice were studied 24h after final exposure, cells and inflammatory mediators were assessed in bronchoalveolar lavage fluid (BALF) and lungs used for evaluation of glucocorticoids receptors (GR), p38 mitogen-activated protein kinase (MAPK) phosphorylation and nuclear transcription factor κB (NF-κB) activation. Exposure to ozone resulted in a marked lung neutrophilia. Moreover, in ozone-exposed group, the levels of oxidative stress-related interleukin (IL)-1β, IL-6, IL-8, IL-17A, activated NF-κB and p38MAPK, airway inflammatory cells infiltration density, mean linear intercept (Lm) were greatly increased, FEV25 and glucocorticoids receptors (GR) were markedly decreased. Comparable to BUD, progesterone treatment dose-dependently led to a significant reduction of IL-1β, IL-6, IL-8, IL-17A, activated NF-κB and p38MAPK, and an increase of FEV25 and GR. Progesterone combined with BUD resulted in dramatic changes, compared to monotherapy of BUD or progesterone. Therefore, these results demonstrate that chronic ozone exposure has profound airway inflammatory effects counteracted by progesterone and progesterone acts synergistically with glucocorticoids in attenuating the airway inflammation dose-dependently. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. The Biology of Progesterone Receptor in the Normal Mammary gland and in Breast Cancer

    Science.gov (United States)

    Obr, Alison; Edwards, Dean P.

    2011-01-01

    This paper reviews work on progesterone and the progesterone receptor (PR) in the mouse mammary gland that has been used extensively as an experimental model. Studies have led to the concept that progesterone controls proliferation and morphogenesis of the luminal epithelium in a tightly orchestrated manner at distinct stages of development by paracrine signaling pathways, including receptor of activated nuclear factor κ ligand (RANKL) as a major paracrine factor. Progesterone also drives expansion of stem cells by paracrine signals to generate progenitors required for alveologenesis. During mid-to-late pregnancy, progesterone has another role to suppress secretory activation until parturition mediated in part by crosstalk between PR and prolactin/Stat5 signaling to inhibit induction of milk protein gene expression, and by inhibiting tight junction closure. In models of hormone-dependent mouse mammary tumors, the progesterone/PR signaling axis enhances pre-neoplastic progression by a switch from a paracrine to an autocrine mode of proliferation and dysregulation of the RANKL signaling pathway. Limited experiments with normal human breast show that progesterone/PR signaling also stimulates epithelial cell proliferation by a paracrine mechanism; however, the signaling pathways and whether RANKL is a major mediator remains unknown. Work with human breast cancer cell lines, patient tumor samples and clinical studies indicates that progesterone is a risk factor for breast cancer and that alteration in progesterone/PR signaling pathways contributes to early stage human breast cancer progression. However, loss of PR expression in primary tumors is associated with a less differentiated more invasive phenotype and worse prognosis, suggesting that PR may limit later stages of tumor progression. PMID:22193050

  14. Hypothalamic effects of progesterone on regulation of the pulsatile and surge release of luteinising hormone in female rats.

    Science.gov (United States)

    He, Wen; Li, Xiaofeng; Adekunbi, Daniel; Liu, Yali; Long, Hui; Wang, Li; Lyu, Qifeng; Kuang, Yanping; O'Byrne, Kevin T

    2017-08-14

    Progesterone can block the oestradiol-induced GnRH/LH surge and inhibit LH pulse frequency. Recent studies reported that progesterone prevented premature LH surges during ovarian hyperstimulation in women. As the most potent stimulator of GnRH/LH release, kisspeptin is believed to mediate the positive and negative feedback effects of oestradiol in the hypothalamic anteroventral periventricular (AVPV) and arcuate (ARC) nuclei, while the region-specific role of progesterone receptors in these nuclei remains unknown. This study examined the hypothesis that progesterone inhibits LH surge and pulsatile secretion via its receptor in the ARC and/or AVPV nuclei. Adult female rats received a single injection of pregnant mare serum gonadotropin followed by progesterone or vehicle. Progesterone administration resulted in a significant prolongation of the oestrous cycle and blockade of LH surge. However, microinjection of the progesterone receptor antagonist, RU486, into the AVPV reversed the prolonged cycle length and rescued the progesterone blockade LH surge, while RU486 into the ARC shortened LH pulse interval in the progesterone treated rats. These results demonstrated that progesterone's inhibitory effect on the GnRH/LH surge and pulsatile secretion is mediated by its receptor in the kisspeptin enriched hypothalamic AVPV and ARC respectively, which are essential for progesterone regulation of oestrous cyclicity in rats.

  15. Endometrial Effects of Prolonged Therapy with the Selective Progesterone Receptor Modulator Ulipristal Acetate: A Case Report.

    Science.gov (United States)

    Levy, Gary; Elkas, John; Armstrong, Alicia Y; Nieman, Lynnette K

    2016-01-01

    Prolonged exposure to a selective progesterone receptor modulator (ulipristal acetate) in a patient with benign metastasizing leiomyoma did not result in endometrial hyperplasia or neoplasia. A woman with history of benign metastasizing leiomyoma underwent medical treatment for 5 years with ulipristal acetate. Endometrial biopsies were performed at established intervals to monitor for intraepithelial neoplasia or progesterone receptor modulator-associated endometrial changes (PAECs). The patient tolerated UPA therapy well; there was no evidence of hyperplasia or proliferative changes associated with progesterone-associated endometrial changes. In this case prolonged exposure to ulipristal acetate did not result in premalignant or malignant endometrial pathology.

  16. Chemical UV filters can affect human sperm function in a progesterone-like manner

    DEFF Research Database (Denmark)

    Rehfeld, Anders; Egeberg, Dorte; Almstrup, Kristian

    2018-01-01

    Human sperm cell function must be precisely regulated to achieve natural fertilization. Progesterone released by the cumulus cells surrounding the egg induces a Ca2+-influx into human sperm cells via the CatSper Ca2+-channel and thereby controls sperm function. Multiple chemical UV filters have...... the effect of progesterone on Ca2+-signaling in human sperm cells, can similarly mimic the effect of progesterone on acrosome reaction and sperm penetration. Human exposure to these chemical UV filters may impair fertility by interfering with sperm function, e.g. through induction of premature acrosome...

  17. Artificial induction of lactation in ewes: the involvement of progesterone and prolactin in lactogenesis.

    Science.gov (United States)

    Fulkerson, W J; Hooley, R D; McDowell, G H; Fell, L R

    1976-10-01

    An attempt has been made to evaluate the importance of prolactin and 'progesterone withdrawal' for lactogenesis. The experimental model system used was the ovariectomized, non-pregnant ewe induced to lactate artifically by treatment with trigger hormone (either oestrogen, glucocorticoid or oxytocin) alone or in combination with progesterone. It appears from the results that prolactin is important in the lactogenic responses elicited by oestrogen and oxytocin but not as important in the response elicited by glucocorticoid. Moreover, the results suggest that, in the ewe, an appropriate positive hormonal stimulus will overcome the inhibitory influence of progesterone on lactogenesis.

  18. Systematic review of progesterone for the prevention of preterm birth in singleton pregnancies

    DEFF Research Database (Denmark)

    Rode, Line; Langhoff-Roos, Jens; Andersson, Charlotte

    2009-01-01

    of preterm delivery in women with preterm labor. CONCLUSIONS: In women with a singleton pregnancy and previous preterm delivery, progesterone reduces the rates of preterm delivery before 32 weeks, perinatal death, as well as respiratory distress syndrome and necrotizing enterocolitis in the newborn. Women...... now showed that progesterone supplementation was associated with a significant reduction of delivery before 32 weeks and of perinatal mortality. Furthermore, a third trial showed a positive effect on women with a short cervix at 23 weeks, and a fourth study showed that progesterone reduces the risk...

  19. Vaginal micronized progesterone and risk of preterm delivery in high-risk twin pregnancies: secondary analysis of a placebo-controlled randomized trial and meta-analysis

    DEFF Research Database (Denmark)

    Klein, K; Rode, L; Nicolaides, K H

    2011-01-01

    Progesterone treatment reduces the risk of preterm delivery in high-risk singleton pregnancies. Our aim was to evaluate the preventive effect of vaginal progesterone in high-risk twins.......Progesterone treatment reduces the risk of preterm delivery in high-risk singleton pregnancies. Our aim was to evaluate the preventive effect of vaginal progesterone in high-risk twins....

  20. Effect of early pregnancy on the expression of progesterone receptor and progesterone-induced blocking factor in ovine lymph node.

    Science.gov (United States)

    Yang, Ling; Zang, Shengqin; Bai, Ying; Yao, Xiaolei; Zhang, Leying

    2017-04-15

    Lymph nodes are the sites where the immune reaction or suppression takes place. Progesterone (P4) exerts an essential effect of the immunomodulation on the maternal uterus during early pregnancy in ruminants. At present study, the inguinal lymph nodes were obtained at day 16 of non-pregnancy, days 13, 16 and 25 of pregnancy (n = 3 for each group) in ewes, and RT-PCR assay, western blot and immunohistochemistry analysis were used to analyze to the effect of early pregnancy on the expression of P4 receptor (PGR) and progesterone-induced blocking factor (PIBF) in the lymph nodes. Our results showed that the PGR and PIBF mRNA were up-regulated in the lymph nodes in pregnant ewes, and the PGR isoform (60 kDa) and the PIBF variant (75 kDa) were expressed constantly in the lymph nodes. However, there was no expression of the PGR isoform (40 kDa) and the PIBF variant (48 kDa) at day 16 of the estrous cycle. The immunohistochemistry results confirmed that the PGR and PIBF proteins were limited to the subcapsular sinus and trabeculae in the cortex, medullary sinuses, and were localized in the cytoplasm of the specific cells. This paper reports for the first time that early pregnancy exerts its effect on the specific cells in the lymph nodes through P4, which results in the up-regulated expression of the PGR mRNA and 40 kDa isoform, the PIBF mRNA and 48 kDa variant, and is involved in the immunoregulation of the lymph nodes through a cytosolic pathway in ewes. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Membrane progesterone receptor beta (mPRβ/Paqr8) promotes progesterone-dependent neurite outgrowth in PC12 neuronal cells via non-G protein-coupled receptor (GPCR) signaling.

    Science.gov (United States)

    Kasubuchi, Mayu; Watanabe, Keita; Hirano, Kanako; Inoue, Daisuke; Li, Xuan; Terasawa, Kazuya; Konishi, Morichika; Itoh, Nobuyuki; Kimura, Ikuo

    2017-07-12

    Recently, sex steroid membrane receptors garnered world-wide attention because they may be related to sex hormone-mediated unknown rapid non-genomic action that cannot be currently explained by their genomic action via nuclear receptors. Progesterone affects cell proliferation and survival via non-genomic effects. In this process, membrane progesterone receptors (mPRα, mPRβ, mPRγ, mPRδ, and mPRε) were identified as putative G protein-coupled receptors (GPCRs) for progesterone. However, the structure, intracellular signaling, and physiological functions of these progesterone receptors are still unclear. Here, we identify a molecular mechanism by which progesterone promotes neurite outgrowth through mPRβ (Paqr8) activation. Mouse mPRβ mRNA was specifically expressed in the central nervous system. It has an incomplete GPCR topology, presenting 6 transmembrane domains and did not exhibit typical GPCR signaling. Progesterone-dependent neurite outgrowth was exhibited by the promotion of ERK phosphorylation via mPRβ, but not via other progesterone receptors such as progesterone membrane receptor 1 (PGRMC-1) and nuclear progesterone receptor in nerve growth factor-induced neuronal PC12 cells. These findings provide new insights of regarding the non-genomic action of progesterone in the central nervous system.

  2. Increasing vaginal progesterone gel supplementation after frozen-thawed embryo transfer significantly increases the delivery rate

    DEFF Research Database (Denmark)

    Alsbjerg, Birgit; Polyzos, Nikolaos P; Elbaek, Helle Olesen

    2013-01-01

    The aim of this study was to evaluate the reproductive outcome in patients receiving frozen-thawed embryo transfer before and after doubling of the vaginal progesterone gel supplementation. The study was a retrospective study performed in The Fertility Clinic, Skive Regional Hospital, Denmark....... A total of 346 infertility patients with oligoamenorrhoea undergoing frozen-thawed embryo transfer after priming with oestradiol and vaginal progesterone gel were included. The vaginal progesterone dose was changed from 90mg (Crinone) once a day to twice a day and the reproductive outcome during the two...... rate (8.7% versus 20.5%, respectively; P=0.002). Doubling of the vaginal progesterone gel supplementation during frozen-thawed embryo transfer cycles decreased the early pregnancy loss rate, resulting in a significantly higher delivery rate. This study evaluated the reproductive outcome of 346 women...

  3. Radioimmunoassay for progesterone in bovine milk; Radioinmunoensayo para progesterona en leche bovina

    Energy Technology Data Exchange (ETDEWEB)

    Ruiz, Miriam [Instituto Superior de Ciencias y Tecnologia Nucleares, La Habana (Cuba)]. E-mail: mirian@fctn.isctn.edu.cu; Figueredo, Nancy; Castillo, Sonia; Pizarro [Centro de Isotopos, La Habana (Cuba)

    2002-07-01

    A system for the measurement of progesterone in bovine milk by radioimmunoassay has been developed and validated. This assay includes an iodine tracer purified by HPLC, the standard prepared in fat-free milk and an antibody anti-progesterone combined with second antibody. The detection limit of the assay is at 0.2 nmol/L calculated from the maximum binding menus two standard deviations and the precision is satisfactory. In the recovery assay was used 4 milk different samples and the result was 98% of recuperation. The progesterone was determinate in milk samples from post-partum animals taking samples three times per week for 40 days. The assay is simple, rapid and possibility the progesterone measurement without sample dilution, distinguish the cyclic changes of this hormone that reflect the ovarian activity in the animals. (author)

  4. Safety of treatment of uterine fibroids with the selective progesterone receptor modulator, ulipristal acetate.

    Science.gov (United States)

    Donnez, Jacques; Donnez, Olivier; Dolmans, Marie-Madeleine

    2016-12-01

    During the last decade, there has been increased emphasis on the role of progesterone in the promotion of fibroid growth, as well as heightened interest in modulating progesterone pathways by use of selective progesterone receptor modulators (SPRMs). Among them, ulipristal acetate (UPA) has proved its efficacy in the management of symptomatic myomas by controlling bleeding and inducing amenorrhea, and reducing the size of myomas in the majority of cases. Areas covered: In this review, we summarize published scientific studies exploring evidence of the safety of SPRMs and particularly UPA, a drug approved for the management of symptomatic uterine fibroids. We focus essentially on endometrial changes induced by UPA, and also evaluate other safety outcomes. Expert opinion: Data from published reports of randomized controlled trials (RCTs) over 5 years have demonstrated that UPA does indeed induce endometrial changes (known as progesterone receptor modulator-associated endometrial changes), but they have been shown to be both benign and reversible.

  5. Vaginal micronized progesterone and risk of preterm delivery in high-risk twin pregnancies

    DEFF Research Database (Denmark)

    Klein, K; Rode, L; Nicolaides, K H

    2011-01-01

    OBJECTIVES: Progesterone treatment reduces the risk of preterm delivery in high-risk singleton pregnancies. Our aim was to evaluate the preventive effect of vaginal progesterone in high-risk twins. METHODS: This was a subanalysis of a Danish-Austrian, double-blind, placebo-controlled, randomized...... trial (PREDICT study), in which women with twin pregnancies were randomized to daily treatment with progesterone or placebo pessaries from 20-24 weeks until 34 weeks' gestation. This subpopulation consisted of high-risk pregnancies, defined by the finding of cervical length ≤ 10th centile at 20-24 weeks...... (10.6%) of the 677 women participating in the PREDICT study, the pregnancy was considered to be high-risk, including 47 with cervical length ≤ 10th centile, 28 with a history of preterm delivery or late miscarriage and three fulfilling both criteria. Baseline characteristics for progesterone...

  6. Expression of Oestrogen and progesterone receptors, Ki-67,p53 and ...

    African Journals Online (AJOL)

    Expression of Oestrogen and progesterone receptors, Ki-67,p53 and bcl-2 proteins, cathepsin D, urokinase plasminogen activator and urokinase plasminogen activator-receptors in carcinomas of the female breast in an African population.

  7. Recent advances in structure of progestins and their binding to progesterone receptors.

    Science.gov (United States)

    Cabeza, Marisa; Heuze, Yvonne; Sánchez, Araceli; Garrido, Mariana; Bratoeff, Eugene

    2015-02-01

    The role of progesterone in women's cancers as well as the knowledge of the progesterone receptor (PR) structure has prompted the design of different therapies. The aim of this review is to describe the basic structure of PR agonists and antagonists as well as the recent treatments for illness associated with the progesterone receptor. The rational design for potent and effective drugs for the treatment of female cancer must consider the structural changes of the androgen and progestogen skeleton which are an indicator of their activity as progestins or antiprogestins. The presence of a hydroxyl group at C-17 in the progesterone skeleton brings about a loss of progestational activity whereas acetylation induces a progestational effect. The incorporation of an ethynyl functional group to the testosterone framework results in a loss of androgenic activity with a concomitant enhancement of the progestational effect. On the other hand, an ester function at C-3 of dehydroepiandrosterone skeleton induces partial antagonism to the PR.

  8. Cloning and initial characterization of nuclear and membrane progesterone receptors in the Fathead Minnow, Pimephales promelas

    Science.gov (United States)

    Both native progestagens and synthetic progestins have important effects on reproduction that are mediated through progesterone receptors (PRs). They regulate gamete maturation and can serve as precursors for other steroid hormones in vertebrates and act as reproductive pheromone...

  9. Control of the Mammary Cell Cycle Clock by Estrogen and Progesterone

    National Research Council Canada - National Science Library

    Weinberg, Robert

    2001-01-01

    Both the growth and the development of the mammary gland are controlled by the female hormones estrogen, prolactin and progesterone, and by interactions between the epithelial and stromal compartments of the breast...

  10. Progesterone receptor content in endometrial carcinoma correlates with serum levels of free estradiol

    DEFF Research Database (Denmark)

    Nyholm, H C; Nielsen, Anette Lynge; Lyndrup, J

    1993-01-01

    cytosol by dextran charcoal-coated assay and immunohistochemically on frozen sections. Serum sex hormones were measured by radioimmunoassays. MAIN FINDINGS. Tumor biochemical progesterone receptor content correlated positively (p

  11. Treatment of postmenopausal women with topical progesterone creams and gels: are they effective?

    Science.gov (United States)

    Stanczyk, F Z

    2014-12-01

    Topical progesterone creams and gels can be obtained over the counter and/or by prescription from custom-compounding pharmacies and are used by thousands of postmenopausal women for hormonal treatment. However, the effectiveness of these preparations for protecting the endometrium from unopposed estrogen is controversial, due largely to the very low serum progesterone levels that are achieved. Despite these low serum levels, salivary and capillary blood levels are very high and a protective endometrium has been reported in a limited number of studies. Topical alcohol-based, but not water-based, gels appear to yield luteal-phase serum progesterone levels but studies with these preparations are scant. Long-term studies with percutaneous progesterone creams and gels are likely to provide valuable information for treatment of postmenopausal women with this popular route of administration.

  12. Estrogen and progesterone receptors in endometrial carcinoma: comparison of immunohistochemical and biochemical analysis

    DEFF Research Database (Denmark)

    Nyholm, H C; Nielsen, Anette Lynge; Lyndrup, J

    1993-01-01

    In 159 endometrial carcinomas, estrogen (ER) and progesterone receptors (PR) were determined biochemically by dextran-coated charcoal (DCC) assay and immunohistochemically (ICA) on frozen sections. ICA receptor content was estimated by a total histologic score (HSCORE), including all tissue...

  13. Immunolocalization of progesterone receptors in binucleate trophoblast cells of the buffalo placenta (Bubalus bubalis

    Directory of Open Access Journals (Sweden)

    Carlos Eduardo Ambrósio

    2007-06-01

    Full Text Available The binucleate trophoblast cells (CTBs of the water buffalo placenta (Bubalus bubalis were studied with emphasis on the presence of progesterone receptor. Placentomal tissues from 27 buffalos (2-10 months of pregnancy were processed and embedded in paraplast (Paraplast Embedding Media – Paraplast Plus to locate the progesterone receptors using the immunohistochemistry technique. The immunohistochemical reaction for progesterone receptor through monoclonal antibody PgR Ab2 showed staining of CTBs, caruncular epithelial and estromal cells and blood vessel estromal pericitos present in the placentome throughout the entire gestational period analyzed. These results indicate the production of progesterone with autocrine and paracrine action in the placentome growth, differentiation and functional regulation.

  14. Expression of estrogen and progesterone receptors in astrocytomas: a literature review

    Directory of Open Access Journals (Sweden)

    Cléciton Braga Tavares

    Full Text Available Gliomas are the most common type of primary central nervous system neoplasm. Astrocytomas are the most prevalent type of glioma and these tumors may be influenced by sex steroid hormones. A literature review for the presence of estrogen and progesterone receptors in astrocytomas was conducted in the PubMed database using the following MeSH terms: “estrogen receptor beta” OR “estrogen receptor alpha” OR “estrogen receptor antagonists” OR “progesterone receptors” OR “astrocytoma” OR “glioma” OR “glioblastoma”. Among the 111 articles identified, 13 studies met our inclusion criteria. The majority of reports showed the presence of estrogen and progesterone receptors in astrocytomas. Overall, higher tumor grades were associated with decreased estrogen receptor expression and increased progesterone receptor expression.

  15. Treatment of cystic ovarian disease in dairy cattle.

    Science.gov (United States)

    Nakao, T; Numata, Y; Kubo, M; Yamauchi, S

    1978-04-01

    Fourty-four Holstein Friesian cows diagnosed as having ovarian follicular cysts from rectal palpation of the ovaries and observation of estrous behavior were used for the present experiments. Of the 16 cows injected intramuscularly (i.m.) with 110 mg of depot-progestins containing 100 mg of 17alpha-hydroxyprogesterone caproate and 10 mg of progesterone in oil, 8 cows responded with conception with 103 +/- 53 days in average after the treatment. The 8 cows not responding to depot-progestins were injected i.m. with 6,000 MU of HCG on the 10th day after the treatment. As a result, 2 cows of them conceived within 72 days in average after the initial treatment. Of the other 16 cows injected i.m. with 100 mg of progesteron in oil, 3 cows conceived. Interval between the treatment and conception was 36 +/- 9 days in average. In the 11 cows which failed to respond to progesterone treatment, an intramuscular injection of 6,000 MU of HCG on the 5th day after treatment resulted in conception of 7 cows within 42 +/- 10 days in average after the first treatment. Of the remaining 12 cows which received an i.m. injection with 10,000 MU of HCG, 4 cows responded with conception with 64 +/- 51 days in average after treatment. No remarkable rise in serum progesterone levels was observed either 10 days after depot-progestins injection or 5 days after progesterone treatment. Serum progesteron levels increased distinctly after HCG injections. The combined treatment with 100 mg of progesterone and 6,000 MU of HCG at 5 days interval gave the most successful results and this treatment was effective even when performed long after calving. Thus this method of treatment of cystic ovarian disease may be recommended for practical application.

  16. REPRODUCTIVE EFFICIENCY AND PROGESTERONE PROFILE FROM PARTURITION TO PARTURITION IN DW ARF GOAT

    OpenAIRE

    Shahnaz A. Khanum, M. Hussain, M. Ali, R. Kausar and A.M. Cheema1

    2001-01-01

    A study was undertaken to look into the reproductive performance of female Dwarf goat. The serum progesterone profile was used to monitor various reproductive parameters including length of postpartum period, the resumption of cyclicity, gestation period, pre-partum period, parturition, litter size and kidding interval. Most of the animals conceived within 20-65 days of postpartum period. During gestation period, higher levels of progesterone were maintained with wide variations falling in th...

  17. Plasma Progesterone Concentrations in Dairy Cows with Cystic Ovaries and Clinical Responses Following Treatment with Fenprostalene

    OpenAIRE

    Leslie, K. E.; Bosu, W. T. K.

    1983-01-01

    Sixty-two dairy cows diagnosed as having cystic ovarian degeneration were used to study the correlation between rectal palpation findings and plasma progesterone concentrations and the response of cysts to treatment using fenprostalene, a luteolytic agent. Rectal palpation accurately determined the presence of luteal cysts as confirmed by plasma progesterone concentrations of 3 ng/mL or more. Treatment with fenprostalene was very effective for luteal cysts: a high percentage of treated cows e...

  18. Chemical UV Filters Mimic the Effect of Progesterone on Ca(2+) Signaling in Human Sperm Cells

    DEFF Research Database (Denmark)

    Rehfeld, A; Dissing, S; Skakkebæk, N E

    2016-01-01

    Progesterone released by cumulus cells surrounding the egg induces a Ca(2+) influx into human sperm cells via the cationic channel of sperm (CatSper) Ca(2+) channel and controls multiple Ca(2+)-dependent responses essential for fertilization. We hypothesized that chemical UV filters may mimic...... competitively inhibited progesterone-induced Ca(2+) signals. In vivo exposure studies are needed to investigate whether UV filter exposure affects human fertility....

  19. Evaluation of Progesterone and Ovulation-stimulating Drugs on the Glandular Epithelium and Angiogenesis in Mice

    Directory of Open Access Journals (Sweden)

    Bahman Rashidi

    2017-01-01

    Full Text Available Background: Human endometrium is a dynamic tissue during the menstrual cycle can be influenced by ovarian hormones. The purpose of this study was to evaluate the endometrium angiogenesis under the influence of human menopausal gonadotropin and human chorionic gonadotropin (HMG and HCG that stimulate ovulation and progesterone. Materials and Methods: In this study, thirty adult female mice were randomly divided into three groups as: control, gonadotropin and gonadotropin + progesterone. The mice in the other two groups except the control group received 7.5 IU HMG and later HCG. Subsequently, the mice were placed in a cage for mating. Gonadotropin + progesterone group was administered, 1 mg/mouse progesterone in 24, 48, and 72 h interval, after HMG injection. Ninety-six hours after HMG injection, animals were sacrificed, and their uterine specimens were prepared by immunohistochemistry technique for light microscopic studies, and statistical analysis was carried out. Results: Endometrium angiogenesis in control group showed that mean ± standard deviation was 24.15 ± 11.15, gonadotropin group was 62.50 ± 24.16, and gonadotropin + progesterone group was 41.85 ± 19.54. Significant difference between the control group and gonadotropin group and between the control group and gonadotropin + progesterone was observed. Statistically significant differences were observed in all groups in the endometrial angiogenesis (P < 0.05. Conclusion: Ovarian induction with gonadotropins and gonadotropins + progesterone could not change the morphometrically index of endometrial glandular epithelium in mice. Ovarian stimulation followed by progesterone injection could modify the angiogenesis of mice endometrium.

  20. Loss of progesterone receptor-mediated actions induce preterm cellular and structural remodeling of the cervix and premature birth.

    Science.gov (United States)

    Yellon, Steven M; Dobyns, Abigail E; Beck, Hailey L; Kurtzman, James T; Garfield, Robert E; Kirby, Michael A

    2013-01-01

    A decline in serum progesterone or antagonism of progesterone receptor function results in preterm labor and birth. Whether characteristics of premature remodeling of the cervix after antiprogestins or ovariectomy are similar to that at term was the focus of the present study. Groups of pregnant rats were treated with vehicle, a progesterone receptor antagonist (onapristone or mifepristone), or ovariectomized on day 17 postbreeding. As expected, controls given vehicle delivered at term while rats delivered preterm after progesterone receptor antagonist treatment or ovariectomy. Similar to the cervix before term, the preterm cervix of progesterone receptor antagonist-treated rats was characterized by reduced cell nuclei density, decreased collagen content and structure, as well as a greater presence of macrophages per unit area. Thus, loss of nuclear progesterone receptor-mediated actions promoted structural remodeling of the cervix, increased census of resident macrophages, and preterm birth much like that found in the cervix at term. In contrast to the progesterone receptor antagonist-induced advance in characteristics associated with remodeling, ovariectomy-induced loss of systemic progesterone did not affect hypertrophy, extracellular collagen, or macrophage numbers in the cervix. Thus, the structure and macrophage census in the cervix appear sufficient for premature ripening and birth to occur well before term. With progesterone receptors predominantly localized on cells other than macrophages, the findings suggest that interactions between cells may facilitate the loss of progesterone receptor-mediated actions as part of a final common mechanism that remodels the cervix in certain etiologies of preterm and with parturition at term.

  1. Enhanced food intake by progesterone-treated female rats is related to changes in neuropeptide genes expression in hypothalamus.

    Science.gov (United States)

    Stelmańska, Ewa; Sucajtys-Szulc, Elżbieta

    2014-01-01

    Progesterone-treated females eat more food, but the mechanism underlying this effect is not well understood. The aim of the study was to analyse the effect of progesterone on neuropeptide genes expression in rat hypothalamus. Experiments were carried out on female and male Wistar rats. Animals were treated with progesterone (100 mg per rat) for 28 days. NPY and CART mRNA levels in hypothalamus were quantified by real-time PCR. The serum progesterone concentration was determined by radioimmunoassay. Progesterone administration to females caused an increase in food intake, body mass, and white adipose tissue mass. Elevated circulating progesterone concentration up-regulated NPY and down-regulated CART genes expression in hypothalamus of females. In males, elevated blood progesterone concentration had no effect on food intake, body and fat mass and on the neuropeptide genes expression in hypothalamus. Moreover, administration of progesterone in females resulted in decrease of PR mRNA level in hypothalamus. No effect of progesterone administration on PR mRNA level in hypothalamus of males was found. The changes in neuropeptide genes expression in hypothalamus may lead to stimulation of appetite and might explain the observed increase in food intake, body and adipose tissue mass in progesterone-treated females.

  2. Does elevated progesterone on day of oocyte maturation play a role in the racial disparities in IVF outcomes?

    Science.gov (United States)

    Hill, Micah J; Royster, G Donald; Taneja, Mansi; Healy, Mae Wu; Zarek, Shvetha M; Christy, Alicia Y; DeCherney, Alan H; Widra, Eric; Devine, Kate

    2017-02-01

    The aim of this study was to evaluate if premature progesterone elevation on the last day of assisted reproduction technique stimulation contributes to racial disparities in IVF outcome. A total of 3289 assisted reproduction technique cycles were evaluated in Latino, Asian, African American, and white women. Live birth was more likely in white women (42.6%) compared with Asian (34.8%) and African American women (36.3%), but was similar to Latino women (40.7%). In all racial groups, progesterone was negatively associated with live birth and the negative effect of progesterone persisted when adjusting for confounders. Although the effect of elevated progesterone was similar in all racial groups, the prevalence of elevated progesterone differed. Progesterone > 1.5 ng/ml occurred in only 10.6% of cycles in white women compared with 18.0% in Latino and 20.2% in Asian women. Progesterone > 2 ng/ml occurred in only 2.3% of cycles in white women compared with 6.3% in Latino, 5.9% in Asian and 4.4% in African American women. The increased prevalence of premature elevated progesterone persisted when controlling for IVF stimulation parameters. In conclusion, premature progesterone elevation had a negative effect on live birth in all racial groups studied. The prevalence of elevated progesterone was higher in racial minorities. Published by Elsevier Ltd.

  3. Plasma progesterone concentrations in dairy cows with cystic ovaries and clinical responses following treatment with fenprostalene.

    Science.gov (United States)

    Leslie, K E; Bosu, W T

    1983-11-01

    Sixty-two dairy cows diagnosed as having cystic ovarian degeneration were used to study the correlation between rectal palpation findings and plasma progesterone concentrations and the response of cysts to treatment using fenprostalene, a luteolytic agent. Rectal palpation accurately determined the presence of luteal cysts as confirmed by plasma progesterone concentrations of 3 ng/mL or more. Treatment with fenprostalene was very effective for luteal cysts: a high percentage of treated cows exhibited estrus within seven days after treatment. The conception rate following artifical insemination during the induced estrus was 87.5% (21/24). Rectal palpation was much less accurate for the diagnosis of follicular cysts. Cows diagnosed as having follicular cysts had wide variations in plasma progesterone concentrations. Response to fenprostalene treatment was poor in cows with nonluteinized cystic follicles associated with low progesterone concentrations. However, cows diagnosed as having follicular cysts, but with progesterone concentrations of 1 ng/mL or more, responded better to fenprostalene treatment than cows with low progesterone concentrations.It was concluded that, if correctly diagnosed, luteal cysts can be successfully treated with fenprostalene, and conception rates following treatment can be expected to be normal.

  4. Cellular Mechanics of Primary Human Cervical Fibroblasts: Influence of Progesterone and a Pro-inflammatory Cytokine.

    Science.gov (United States)

    Shukla, Vasudha; Barnhouse, Victoria; Ackerman, William E; Summerfield, Taryn L; Powell, Heather M; Leight, Jennifer L; Kniss, Douglas A; Ghadiali, Samir N

    2018-01-01

    The leading cause of neonatal mortality, pre-term birth, is often caused by pre-mature ripening/opening of the uterine cervix. Although cervical fibroblasts play an important role in modulating the cervix's extracellular matrix (ECM) and mechanical properties, it is not known how hormones, i.e., progesterone, and pro-inflammatory insults alter fibroblast mechanics, fibroblast-ECM interactions and the resulting changes in tissue mechanics. Here we investigate how progesterone and a pro-inflammatory cytokine, IL-1β, alter the biomechanical properties of human cervical fibroblasts and the fibroblast-ECM interactions that govern tissue-scale mechanics. Primary human fibroblasts were isolated from non-pregnant cervix and treated with estrogen/progesterone, IL-1β or both. The resulting changes in ECM gene expression, matrix remodeling, traction force generation, cell-ECM adhesion and tissue contractility were monitored. Results indicate that IL-1β induces a significant reduction in traction force and ECM adhesion independent of pre-treatment with progesterone. These cell level effects altered tissue-scale mechanics where IL-1β inhibited the contraction of a collagen gel over 6 days. Interestingly, progesterone treatment alone did not modulate traction forces or gel contraction but did result in a dramatic increase in cell-ECM adhesion. Therefore, the protective effect of progesterone may be due to altered adhesion dynamics as opposed to altered ECM remodeling.

  5. Expression of estrogen and progesterone receptors in vestibular schwannomas and their clinical significance

    Directory of Open Access Journals (Sweden)

    Pandey Rakesh

    2009-11-01

    Full Text Available Abstract Objective The objective was to determine the expression of estrogen and progesterone receptors in vestibular schwannomas as well as to determine predictive factors for estrogen and progesterone receptor positivity. Materials and methods The study included 100 cases of vestibular schwannomas operated from January 2006 to June 2009. The clinical details were noted from the medical case files. Formaldehyde-fixed parafiin-embedded archival vestibular schwannomas specimens were used for the immunohistochemical assessment of estrogen and progesterone receptors. Results Neither estrogen nor progesterone receptors could be detected in any of our cases by means of well known immunohistochemical method using well documented monoclonal antibodies. In the control specimens, a strongly positive reaction could be seen. Conclusion No estrogen and progesterone receptor could be found in any of our 100 cases of vestibular schwannomas. Hence our study does not support a causative role of estrogen and progesterone in the growth of vestibular schwannoma as well as hormonal manipulation in the treatment of this tumor.

  6. Metabolic level recognition of progesterone in dairy Holstein cows using probabilistic models

    Directory of Open Access Journals (Sweden)

    Ludmila N. Turino

    2014-05-01

    Full Text Available Administration of exogenous progesterone is widely used in hormonal protocols for estrous (resynchronization of dairy cattle without regarding pharmacological issues for dose calculation. This happens because it is difficult to estimate the metabolic level of progesterone for each individual cow before administration. In the present contribution, progesterone pharmacokinetics has been determined in lactating Holstein cows with different milk production yields. A Bayesian approach has been implemented to build two probabilistic progesterone pharmacokinetic models for high and low yield dairy cows. Such models are based on a one-compartment Hill structure. Posterior probabilistic models have been structurally set up and parametric probability density functions have been empirically estimated. Moreover, a global sensitivity analysis has been done to know sensitivity profile of each model. Finally, posterior probabilistic models have adequately recognized cow’s progesterone metabolic level in a validation set when Kullback-Leibler based indices were used. These results suggest that milk yield may be a good index for estimating pharmacokinetic level of progesterone.

  7. The effect of prenatally administered vaginal progesterone on uterine artery Doppler in asymptomatic twin pregnancies.

    Science.gov (United States)

    Agra, Isabela K R; Brizot, Maria L; Miyadahira, Mariana Y; Carvalho, Mário H B; Francisco, Rossana P V; Zugaib, Marcelo

    2016-10-01

    This study investigated the influence of vaginal progesterone on uterine circulation in asymptomatic twin gestations. This study was a secondary analysis of a randomized, double-blind, placebo-controlled trial of twin pregnancies exposed to vaginal progesterone or placebo. We included all trial participants who had undergone uterine artery pulsatility index evaluation at the time of randomization. During each ultrasound examination, the uterine artery pulsatility index was evaluated transabdominally. The mean uterine artery pulsatility index between the progesterone and placebo groups were compared for each gestational age, starting between 18 to 34 weeks and 6days and were analyzed at three (Time 1), six (Time 2) and nine (Time 3) weeks after randomization. The final analysis included 128 women in the progesterone group and 122 women in the placebo group. The baseline characteristics were similar in both groups. No difference in the mean uterine artery pulsatility index was observed between the progesterone and placebo groups at each week of gestation or throughout gestation. In twin pregnancies, the use of vaginal progesterone in the second half of pregnancy does not influence uterine circulation. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  8. A Gata2-Dependent Transcription Network Regulates Uterine Progesterone Responsiveness and Endometrial Function

    Directory of Open Access Journals (Sweden)

    Cory A. Rubel

    2016-10-01

    Full Text Available Altered progesterone responsiveness leads to female infertility and cancer, but underlying mechanisms remain unclear. Mice with uterine-specific ablation of GATA binding protein 2 (Gata2 are infertile, showing failures in embryo implantation, endometrial decidualization, and uninhibited estrogen signaling. Gata2 deficiency results in reduced progesterone receptor (PGR expression and attenuated progesterone signaling, as evidenced by genome-wide expression profiling and chromatin immunoprecipitation. GATA2 not only occupies at and promotes expression of the Pgr gene but also regulates downstream progesterone responsive genes in conjunction with the PGR. Additionally, Gata2 knockout uteri exhibit abnormal luminal epithelia with ectopic TRP63 expressing squamous cells and a cancer-related molecular profile in a progesterone-independent manner. Lastly, we found a conserved GATA2-PGR regulatory network in both human and mice based on gene signature and path analyses using gene expression profiles of human endometrial tissues. In conclusion, uterine Gata2 regulates a key regulatory network of gene expression for progesterone signaling at the early pregnancy stage.

  9. The impact of progesterone on memory consolidation of threatening images in women.

    Science.gov (United States)

    Felmingham, Kim L; Fong, Wing Chee; Bryant, Richard A

    2012-11-01

    Recent findings suggest that consolidation of emotional memories is influenced by menstrual phase in women. In contrast to other phases, in the mid-luteal phase when progesterone levels are elevated, cortisol levels are increased and correlated with emotional memory. This study examined the impact of progesterone on cortisol and memory consolidation of threatening stimuli under stressful conditions. Thirty women were recruited for the high progesterone group (in the mid-luteal phase) and 26 for the low progesterone group (in non-luteal phases of the menstrual cycle). Women were shown a series of 20 neutral or threatening images followed immediately by either a stressor (cold pressor task) or control condition. Participants returned two days later for a surprise free recall test of the images and salivary cortisol responses were monitored. High progesterone levels were associated with higher baseline and stress-evoked cortisol levels, and enhanced memory of negative images when stress was received. A positive correlation was found between stress-induced cortisol levels and memory recall of threatening images. These findings suggest that progesterone mediates cortisol responses to stress and subsequently predicts memory recall for emotionally arousing stimuli. Copyright © 2012 Elsevier Ltd. All rights reserved.

  10. Sex-related differences in effects of progesterone following neonatal hypoxic brain injury.

    Science.gov (United States)

    Peterson, Bethany L; Won, Soonmi; Geddes, Rastafa I; Sayeed, Iqbal; Stein, Donald G

    2015-06-01

    There is no satisfactory therapeutic intervention for neonatal hypoxic-ischemic (HI) encephalopathy. Progesterone is known to be effective in treating traumatic brain injury in adult animals but its effects in neonatal brains have not been reported. Brain injuries were induced by a unilateral common carotid artery ligation plus hypoxia exposure. Progesterone was administered immediately after hypoxia and daily for 5 days at 8 mg/kg, followed by a tapered dose for two days. At six weeks post-injury, lesion size and inflammatory factors were evaluated. Progesterone-treated, HI-injured male animals, but not females, showed significant long-term tissue protection compared to vehicle, suggesting an important sex difference in neuroprotection. Progesterone-treated, HI-injured male rats had fewer activated microglia in the cortex and hippocampus compared to controls. The rats were tested for neurological reflexes, motor asymmetry, and cognitive performance at multiple time points. The injured animals exhibited few detectable motor deficits, suggesting a high level of age- and injury-related neuroplasticity. There were substantial sex differences on several behavioral tests, indicating that immature males and females should be analyzed separately. Progesterone-treated animals showed modest beneficial effects in both sexes compared to vehicle-treated injured animals. Sham animals given progesterone did not behave differently from vehicle-treated sham animals on any measures. Copyright © 2015 Elsevier B.V. All rights reserved.

  11. Effects of interactions between progesterone and prostaglandin on uterine contractility in a perfused swine uterus model.

    Science.gov (United States)

    Künzel, Julian; Geisler, Klaudija; Maltaris, Theodoros; Müller, Andreas; Hoffmann, Inge; Schneider, Heike; Beckmann, Matthias W; Dittrich, Ralf; Oppelt, Patricia G

    2014-01-01

    Uterine quiescence at the time of embryo transfer is a prerequisite for successful in vitro fertilization (IVF). This study assessed whether prostaglandin-induced contractions in the perfused swine uterus can be reduced by progesterone. Fifty-eight non-pregnant swine uteri were perfused using an established extracorporeal perfusion model. Intrauterine pressure changes during perfusion with prostaglandin (PG) administration (PGE1, PGE2, PGF2α) and progesterone (1 pg/ml, 10 pg/ml, 25 pg/ml, 50 pg/ml) were assessed using an intrauterine double-chip microcatheter. The contraction-stimulating effect of PGs was clearly reduced by progesterone. Only PGE1 still triggered relevant contractions during continuous perfusion with progesterone solution, up to a concentration of 10 pg/ml. With PGE2 and PGF2α, a clear reduction of uterine contractility was observed even at at a progesterone concentration of 1 pg/ml. The extracorporal perfusion model of swine uteri shows that PG-induced contractions can be reduced in a dose-dependent manner by progesterone. Copyright © 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  12. MECHANISMS RESPONSIBLE FOR PROGESTERONE’S PROTECTION AGAINST LORDOSIS-INHIBITING EFFECTS OF RESTRAINT I. ROLE OF PROGESTERONE RECEPTORS

    Science.gov (United States)

    Hassell, James; Miryala, Chandra Suma Johnson; Hiegel, Cindy

    2011-01-01

    Progestins and antiprogestins are widely used therapeutic agents in humans. In many cases, these are indicated for the treatment of reproductive activites. However, progesterone has widespread physiological effects including a reduction of the response to stress. We have reported that 5 min of restraint reduced lordosis behavior of ovariectomized rats hormonally primed with estradiol benzoate. When ovariectomized rats received both estradiol benzoate and progesterone priming, restraint had minimal effects on lordosis. Progesterone influences behavior through classical intracellular progesterone receptor-mediated nuclear events as well as extranuclear events. How these multiple events contribute to the response to stress are unclear. The current project was designed to initiate examination of the mechanisms responsible for progesterone’s ability to protect against the effects of the restraint. In the first experiment, ovariectomized rats, primed with 10 µg estradiol benzoate, received 500 µg progesterone 4 hr, 1 hr, or 30 min before restraint. When progesterone was injected 4 hr before restraint, progesterone eliminated the effects of restraint. In contrast, progesterone 30 min before restraint offered no protection. Effects of progesterone 1 hr before restraint were equivocal allowing the suggestion that less than 4 hr of progesterone priming might be sufficient. In the second experiment, the synthetic progestin, medroxyprogesterone, was shown to mimic effects of progesterone in preventing effects of restraint. Finally, the progesterone receptor antagonist, RU486, attenuated progesterone’s protection against restraint. These findings offer evidence that ligand-activated progesterone receptor mechanisms contribute to the maintenance of lordosis behavior in the presence of mild stress. PMID:21635894

  13. Vaginal ring delivery of selective progesterone receptor modulators for contraception

    Science.gov (United States)

    Jensen, Jeffrey T.

    2013-01-01

    Vaginal ring delivery of selective progesterone receptor modulators (SPRMs) are under development to address limitations of current hormonal methods that affect use and effectiveness. This method would be appropriate for use in women with contraindications to, or preferences to avoid, estrogens. A contraceptive vaginal ring (CVR) also eliminates the need for daily dosing, and therefore might improve the effectiveness of contraception. The principle contraceptive effect of SPRMs is the suppression of ovulation. One limiting factor of chronic SPRM administration is the development of benign endometrial thickening characterized as PRM-associated endometrial changes. Ulipristal acetate is approved for use as an emergency contraceptive pill, but no SPRM is approved for regular contraception. The Population Council is developing an ulipristal acetate CVR for regular contraception. The CVR studied is of a matrix design composed of micronized UPA mixed in a silicone rubber matrix The target product is a ring designed for continuous use over 3 months delivering near steady-state drug levels that will suppress ovulation. Results from Phase 1–2 studies demonstrate that suppression of ovulation occurs with UPA levels above 6–7 ng/mL. PMID:23040126

  14. Bone growth and turnover in progesterone receptor knockout mice.

    Energy Technology Data Exchange (ETDEWEB)

    Rickard, David J.; Iwaniec, Urszula T.; Evans, Glenda; Hefferan, Theresa E.; Hunter, Jaime C.; Waters, Katrina M.; Lydon, John P.; O' Malley, Bert W.; Khosla, Sundeep; Spelsberg, Thomas C.; Turner, Russell T.

    2008-05-01

    The role of progesterone receptor (PR) signaling in skeletal metabolism is controversial. To address whether signaling through the PR is necessary for normal bone growth and turnover, we performed histomorphometric and mCT analyses of bone from homozygous female PR knockout (PRKO) mice at 6, 12, and 26 weeks of age. These mice possess a null mutation of the PR locus, which blocks the gene expression of A and B isoforms of PR. Body weight gain, uterine weight gain and tibia longitudinal bone growth was normal in PRKO mice. In contrast, total and cortical bone mass were increased in long bones of post-pubertal (12 and 26-week-old) PRKO mice, whereas cancellous bone mass was normal in the tibia but increased in the humerus. The striking 57% decrease in cancellous bone from the proximal tibia metaphysis which occurred between 6 and 26 weeks in WT mice was abolished in PRKO mice. The improved bone balance in aging PRKO mice was associated with elevated bone formation and a tendency toward reduced osteoclast perimeter. Taken together, these findings suggest that PR signaling in mice attenuates the accumulation of cortical bone mass during adolescence and is required for early age-related loss of cancellous bone.

  15. Sensorimotor development in neonatal progesterone receptor knockout mice.

    Science.gov (United States)

    Willing, Jari; Wagner, Christine K

    2014-01-01

    Early exposure to steroid hormones can permanently and dramatically alter neural development. This is best understood in the organizational effects of hormones during development of brain regions involved in reproductive behaviors or neuroendocrine function. However, recent evidence strongly suggests that steroid hormones play a vital role in shaping brain regions involved in cognitive behavior such as the cerebral cortex. The most abundantly expressed steroid hormone receptor in the developing rodent cortex is the progesterone receptor (PR). In the rat, PR is initially expressed in the developmentally-critical subplate at E18, and subsequently in laminas V and II/III through the first three postnatal weeks (Quadros et al. [2007] J Comp Neurol 504:42-56; Lopez & Wagner [2009]: J Comp Neurol 512:124-139), coinciding with significant periods of dendritic maturation, the arrival of afferents and synaptogenesis. In the present study, we investigated PR expression in the neonatal mouse somatosensory cortex. Additionally, to investigate the potential role of PR in developing cortex, we examined sensorimotor function in the first two postnatal weeks in PR knockout mice and their wildtype (WT) and heterozygous (HZ) counterparts. While the three genotypes were similar in most regards, PRKO and HZ mice lost the rooting reflex 2-3 days earlier than WT mice. These studies represent the first developmental behavioral assessment of PRKO mice and suggest PR expression may play an important role in the maturation of cortical connectivity and sensorimotor integration. Copyright © 2013 Wiley Periodicals, Inc.

  16. The Effects of Progesterone on Oocyte Maturation and Embryo Development

    Directory of Open Access Journals (Sweden)

    Saeed Zavareh

    2013-01-01

    Full Text Available Oocyte maturation and embryo development are controlled by intra-ovarian factors suchas steroid hormones. Progesterone (P4 exists in the follicular fluid that contributes tonormal mammalian ovarian function and has several critical functions during embryodevelopment and implantation, including endometrial receptivity, embryonic survivalduring gestation and transformation of the endometrial stromal cells to decidual cells.It is well known that the physiological effects of P4 during the pre-implantation stages ofsome mammal’s embryos are mediated by P4 receptors and their gene expression is determined.The effects of P4 on oocytes and embryo development have been assessed bysome investigations, with contradictory results. P4, a dominant steroid in follicular fluidat approximately 18 hours after the luteinizing hormone (LH surge may have a criticalrole in maturation of oocytes at the germinal stage. However, it has been shown that differentconcentrations of P4 could not improve in vitro maturation rates of germinal vesicles(GV in cumulus oocyte complexes (COCs and cumulus denuded oocytes (CDOs.Culture media supplemented with P4 significantly improved mouse embryo development.In addition, an in vivo experimental design has shown high blastocyst survival andimplantation rates in P4-treated mice.In this review we explain some of the findings that pertain to the effects of P4 onoocyte maturation and embryo development both in vitro and in vivo.

  17. Estrogen and Progesterone hormone receptor expression in oral cavity cancer.

    Science.gov (United States)

    Grimm, M; Biegner, T; Teriete, P; Hoefert, S; Krimmel, M; Munz, A; Reinert, S

    2016-09-01

    Recent studies have shown an increase in the incidence of oral squamous cell carcinoma (OSCC) in younger patients. The hypothesis that tumors could be hormonally induced during pregnancy or in young female patients without the well-known risk factors alcohol or tobacco abuse seems to be plausible. Estrogen Receptor alpha (ERα) and Progesterone Receptor (PR) expression were analyzed in normal oral mucosa (n=5), oral precursor lesions (simple hyperplasia, n=11; squamous intraepithelial neoplasia, SIN I-III, n=35), and OSCC specimen. OSCCs were stratified in a young female (n=7) study cohort and older patients (n=46). In the young female study cohort three patients (n=3/7) developed OSCC during or shortly after pregnancy. Breast cancer tissues were used as positive control for ERα and PR expression. ERα expression was found in four oral precursor lesions (squamous intraepithelial neoplasia, SIN I-III, n=4/35, 11%) and in five OSCC specimen (n=5/46, 11%). The five ERα positive OSCC samples were older male patients. All patients within the young female study cohort were negatively stained for both ERα and PR. ER expression could be regarded as a seldom risk factor for OSCC. PR expression seems to be not relevant for the development of OSCC.

  18. Effects of progesterone stimulated allopregnanolone on craving and stress response in cocaine dependent men and women.

    Science.gov (United States)

    Milivojevic, Verica; Fox, Helen C; Sofuoglu, Mehmet; Covault, Jonathan; Sinha, Rajita

    2016-03-01

    Fluctuations in progesterone levels during the menstrual cycle have been shown to affect physiological and subjective effects of cocaine. Furthermore, our laboratory has demonstrated that following drug-cue exposure, cocaine dependent women with high levels of circulating progesterone display lower diastolic and systolic blood pressure responses and report lower levels of anxiety and drug craving compared to cocaine dependent women with low levels of progesterone. In the current study we examined the role of the progesterone derived neuroactive steroid allopregnanolone (ALLO) on stress arousal, inhibitory control and drug craving in cocaine dependent subjects. Plasma levels of ALLO were measured using GC/MS in 46 treatment-seeking cocaine dependent men and women on day 5 of a 7-day treatment regimen of micronized progesterone (15M/8F) (400mg/day) or placebo (14M/9F) administered in a double blind, randomized manner. As a control, levels of the testosterone derived neurosteroid androstanediol (ADIOL) were also measured. All subjects participated in laboratory sessions on days 5-7 of progesterone/placebo administration in which they were exposed to a series of 5-min personalized guided imagery of either a stressful situation, cocaine use or of a neutral setting and dependent variables including subjective craving, mood, Stroop task as a measure of inhibitory control performance and plasma cortisol were assessed. Participants were grouped by high or low ALLO level and levels of dependent variables compared between ALLO groups. Progesterone relative to placebo significantly increased ALLO levels with no sex differences. There were no effects of micronized progesterone on the testosterone derived ADIOL. Individuals in the high versus the low ALLO group showed decreased levels of cortisol at baseline, and a higher cortisol response to stress; higher positive mood scores at baseline and improved Stroop performance in the drug-cue and stress conditions, and reduced cocaine

  19. Progesterone withdrawal effects in the open field test can be predicted by elevated plus maze performance.

    Science.gov (United States)

    Löfgren, Magnus; Johansson, Inga-Maj; Meyerson, Bengt; Lundgren, Per; Bäckström, Torbjörn

    2006-08-01

    Allopregnanolone (3alpha-hydroxy-5alpha-pregnane-20-one) is a ring-A-reduced metabolite of progesterone, which is naturally produced during the luteal phase of the menstrual cycle, during pregnancy and by stressful events. The steroid hormone inhibits neural functions through increased chloride ion flux through the GABA(A) receptor. The effects and subsequent withdrawal symptoms are similar to those caused by alcohol, benzodiazepines and barbiturates. This study examined the withdrawal effects of progesterone with regards to the influence of individual baseline exploration and risk taking. Rats were tested on the elevated plus maze (EPM) before hormonal treatment, in order to evaluate differences in risk taking and exploration of open and elevated areas. Treatment consisted of ten consecutive once a day progesterone or vehicle s.c. injections. On the last day of treatment, estradiol was injected in addition to progesterone, followed by a 24-h withdrawal before testing in the open field test (OF). Progesterone-treated rats showed a withdrawal effect of open area avoidance in the OF. The vehicle-treated control rats showed strong correlations between the EPM and OF parameters. This relationship was not found for the progesterone group at withdrawal. Rats with greater numbers of open arm entrance in the EPM pretest showed an increased sensitivity to progesterone withdrawal (PWD) compared to rats with low exploration and risk taking. The results indicate that the effects of PWD relate to individual exploration and risk taking. Furthermore, the possible analogy of PWD and PMS/PMDD in relation to individual traits is discussed.

  20. Luteal phase support in assisted reproductive technology treatment: focus on Endometrin® (progesterone vaginal insert

    Directory of Open Access Journals (Sweden)

    Jerome H Check

    2009-05-01

    Full Text Available Jerome H CheckThe University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School at Camden, Cooper Hospital/University Medical Center, Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology and Infertility, Camden, New Jersey, USAAbstract: Supplementation of progesterone in the luteal phase and continuance of progesterone therapy during the first trimester has been found in several studies to have benefits in promoting fertility, preventing miscarriages and even preventing pre-term labor. Though it can be administered orally, intramuscularly or even sublingually, a very effective route with fewer side effects can be achieved by an intravaginal route. The first vaginal preparations were not made commercially but were compounded by pharmacies. This had the disadvantage of lack of control by the Food and Drug Administration (FDA ensuring efficacy of the preparations. Furthermore there was a lack of precise dosing leading to batch to batch variation. The first commercially approved vaginal progesterone preparation in the United States was a vaginal gel which has proven very effective. The main side effect was accumulation of a buildup of the vaginal gel sometimes leading to irritation. Natural micronized progesterone for vaginal administration with the brand name of Utrogestan A® had been approved even before the gel in certain European countries. Endometrin® vaginal tablets are the newest natural progesterone approved by the FDA. Comparisons to the vaginal gel and to intramuscular progesterone have shown similar efficacy especially in studies following controlled ovarian hyperstimulation and oocyte egg retrieval and embryo transfer. Larger studies are needed to compare side effects.Keywords: progesterone vaginal tablets, luteal phase, miscarriage, pregnancy rates

  1. Progesterone for smoking relapse prevention following delivery: A pilot, randomized, double-blind study.

    Science.gov (United States)

    Forray, Ariadna; Gilstad-Hayden, Kathryn; Suppies, Cristine; Bogen, Debra; Sofuoglu, Mehmet; Yonkers, Kimberly A

    2017-12-01

    Close to half of women who were smokers prior to conception quit smoking in pregnancy, when endogenous progesterone levels are high. However, at least half resume pre-pregnancy smoking levels within weeks after delivery and when progesterone levels drop. The current pilot study tested the feasibility and preliminary efficacy of postpartum progesterone replacement in preventing relapse to smoking in postpartum women with a history of pre-pregnancy smoking. This was an 8-week, double-blind, parallel, randomized, placebo-controlled pilot trial of 41 women with a history of pre-pregnancy smoking who achieved abstinence by 32 weeks of gestation. Immediately following delivery women were randomized to oral micronized progesterone (200mg twice daily) or placebo via computerized urn randomization program. The main outcome measures were descriptions of study feasibility: recruitment and retention. Secondary outcomes were 7-day point prevalence of abstinence at week 8, time to relapse and smoking cravings. The trial was feasible with adequate randomization, 64% (41/64) of eligible women, and trial retention, 78% (32/41) completed the trial. Women taking progesterone were 1.8 times more likely to be abstinent during week 8 and took longer to relapse (10 vs. 4 weeks) compared to the placebo group, although these differences did not reach statistical significance. After adjusting for age and pre-quit smoking level, the number needed to treat was 7. There was a 10% greater decline per week in craving ratings in the progesterone group compared to placebo (β=-0.10, 95% CI: -0.15, -0.04, p<0.01). No serious adverse events occurred during the trial. These preliminary findings support the promise of progesterone treatment in postpartum smokers and could constitute a therapeutic breakthrough.If these preliminary findings can be evaluated and replicated in a larger study with sufficient power, this may constitute an acceptable and safe smoking relapse prevention strategy for use

  2. Progesterone attenuates astro- and microgliosis and enhances oligodendrocyte differentiation following spinal cord injury.

    Science.gov (United States)

    Labombarda, Florencia; González, Susana; Lima, Analia; Roig, Paulina; Guennoun, Rachida; Schumacher, Michael; De Nicola, Alejandro F

    2011-09-01

    Reactive gliosis, demyelination and proliferation of NG2+ oligodendrocyte precursor cells (OPC) are common responses to spinal cord injury (SCI). We previously reported that short-term progesterone treatment stimulates OPC proliferation whereas chronic treatment enhances OPC differentiation after SCI. Presently, we further studied the proliferation/differentiation of glial cells involved in inflammation and remyelination in male rats with SCI subjected to acute (3 days) or chronic (21 days) progesterone administration. Rats received several pulses of bromodeoyuridine (BrdU) 48 and 72 h post-SCI, and sacrificed 3 or 21 days post-SCI. Double colocalization of BrdU and specific cell markers showed that 3 days of SCI induced a strong proliferation of S100β+ astrocytes, OX-42+ microglia/macrophages and NG2+ cells. At this stage, the intense GFAP+ astrogliosis was BrdU negative. Twenty one days of SCI enhanced maturation of S100β+ cells into GFAP+ astrocytes, but decreased the number of CC1+ oligodendrocytes. Progesterone treatment inhibited astrocyte and microglia /macrophage proliferation and activation in the 3-day SCI group, and inhibited activation in the 21-day SCI group. BrdU/NG2 double labeled cells were increased by progesterone at 3 days, indicating a proliferation stimulus, but decreased them at 21 days. However, progesterone-enhancement of CC1+/BrdU+ oligodendrocyte density, suggest differentiation of OPC into mature oligondendrocytes. We conclude that progesterone effects after SCI involves: a) inhibition of astrocyte proliferation and activation; b) anti-inflammatory effects by preventing microglial activation and proliferation, and c) early proliferation of NG2+ progenitors and late remyelination. Thus, progesterone behaves as a glioactive factor favoring remyelination and inhibiting reactive gliosis. Copyright © 2011 Elsevier Inc. All rights reserved.

  3. Prenatal administration of vaginal progesterone and frequency of uterine contractions in asymptomatic twin pregnancies.

    Science.gov (United States)

    de Oliveira, Lília A M L; Brizot, Maria L; Liao, Adolfo W; Bittar, Roberto E; Francisco, Rossana P V; Zugaib, Marcelo

    2016-04-01

    A previous study indicated that progesterone reduces the mean uterine contraction frequency in singleton pregnancy at high risk for preterm birth. The aim of this study was to investigate the effect of vaginal progesterone on the frequency of uterine contractions in twin pregnancies. This was a secondary analysis of a randomized, double-blind, placebo-controlled trial of twin pregnancies exposed to vaginal progesterone or placebo. Naturally conceived twin pregnancies with no prior history of preterm delivery, asymptomatic regarding preterm labor, who had undergone uterine contraction frequency monitoring from 24 to 34 weeks and 6 days were included in the study. Comparison of the mean frequency of uterine contractions between the treatment groups was performed. We also examined the influence of cervical length and chorionicity on the mean frequency of uterine contractions according to the group. The final analysis included 166 women in the progesterone and 170 in the placebo group. The baseline characteristics were similar in the two groups. Overall, no difference in the mean frequency of uterine contractions (p = 0.91) was observed between the progesterone (2.54 ± 3.19) and placebo (2.56 ± 3.59) groups. Also, no difference in the mean frequency of uterine contractions was observed between the groups in each week between 24 and 34 weeks and 6 days of gestation. Cervical length and chorionicity did not influence the frequency of contractions according to the progesterone or placebo treatment. Overall, progesterone does not influence the frequency of uterine contractions in twin pregnancies. © 2016 Nordic Federation of Societies of Obstetrics and Gynecology.

  4. miR-129-2 mediates down-regulation of progesterone receptor in response to progesterone in breast cancer cells

    Science.gov (United States)

    Godbole, Mukul; Chandrani, Pratik; Gardi, Nilesh; Dhamne, Hemant; Patel, Kuldeep; Yadav, Neelima; Gupta, Sudeep; Badwe, Rajendra

    2017-01-01

    ABSTRACT Objective: Hormonal therapy is an important component of first line of treatment for breast cancer. Response to hormonal therapy is influenced by the progesterone receptor (PR)-status of breast cancer patients. However as an early effect, exposure to progesterone decreases expression of PR in breast cancer cells. An understanding of the mechanism underlying down-regulation of PR could help improve response to hormonal therapy. Methods: We performed small RNA sequencing of breast cancer cells for identification of microRNAs targeting PR in response to progesterone treatment. Biochemical approaches were used to validate the findings in breast cancer cells. Results: Analysis of small RNA sequencing of four breast cancer cell lines treated with progesterone revealed an up-regulation of miR-129-2 independent of the PR status of the cells. We show that miR-129-2 targets 3′UTR of PR to down-regulate its expression. Furthermore, inhibition of miR-129-2 expression rescues the down-regulation of PR in breast cancer cells. Also, the expression levels of miR-129-2 was observed to be elevated in patients with low expression of PR in the TCGA cohort (n = 359). Conclusion: miR-129-2 mediates down-regulation of PR in breast cancer cells in response to progesterone, while anti-miR-129-2 could potentiate PR expression levels among patients with inadequate PR levels. Thus, modulation of activity of miR-129-2 could stabilize PR expression and potentially improve response to hormonal therapy under adjuvant or neo-adjuvant settings. PMID:28876975

  5. In-vitro study of gonadotrophin signaling pathways in human granulosa cells in relation to progesterone receptor expression.

    Science.gov (United States)

    Henríquez, Soledad; Kohen, Paulina; Muñoz, Alex; Godoy, Ana; Orge, Felipe; Strauss, Jerome F; Devoto, Luigi

    2017-10-01

    In humans, data on gonadotrophin-activated (LH, HCG and FSH) progesterone receptor expression and signalling pathways involved in matrix metalloproteinases (MMPs) expression presumably linked to the follicle rupture, are limited. Our hypothesis is LH, HCG and FSH increase progesterone receptor expression in granulosa cells through different signalling pathways, leading to an increased expression of ADAMTS-1 and MMP3/10, which may mediate follicular rupture through the transcription factor, HIF1A. Human granulosa cells were isolated from follicular aspirates obtained from 22 healthy women participating in our IVF programme for male-factor infertility. Progesterone receptor and HIF1A expression was assessed by immunofluorescence, and PKA-PKC-PI3K- ERK1/2, ADAMTS-1 and MMP3/10 expression by Western blot in pre-ovulatory and in cultured granulosa cells. Results show that HCG, LH and FSH regulate progesterone receptor expression and activate PKA, PKC, PI3K and ERK1/2 signalling pathways in granulosa cells but progesterone receptor expression is only mediated by PKA, PKC and ERK pathways. HCG, FSH and LH regulated MMPs expression through progesterone receptors. Moreover, HCG-progesterone-receptor-dependent HIF1A expression stimulated MMP3/10 expression but not that of ADAMTS-1. These results suggest differential downstream progesterone receptor signalling, as progesterone receptor regulates MMP3/10 expression via HIF1A, which is not involved in ADAMTS-1 expression. Copyright © 2017 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

  6. Progesterone co-administration in patients discontinuing long-term benzodiazepine therapy: effects on withdrawal severity and taper outcome.

    Science.gov (United States)

    Schweizer, E; Case, W G; Garcia-Espana, F; Greenblatt, D J; Rickels, K

    1995-02-01

    Since recent research has suggested that the major metabolites of progesterone are barbiturate-like modulators of GABAergic function, we undertook a pilot study of the efficacy of micronized progesterone in attenuating withdrawal and facilitating discontinuation in benzodiazepine-dependent patients with a minimum of 1 year of continuous daily use. Forty-three patients taking a mean daily dose of 16.2 mg of diazepam (or its equivalent) were assigned, doubleblind, to treatment with either placebo (n = 13) or progesterone (n = 30). Progesterone was titrated to a mean daily dose of 1983 mg, and was co-administered for 3 weeks, after which the benzodiazepine was tapered by 25% per week. Progesterone (or placebo) was then continued for 4 weeks before being discontinued. There was no progesterone versus placebo difference in the severity of taper withdrawal. Withdrawal checklist change scores were 17.3 for progesterone and 16.5 for placebo (F 0.63; df 2.31; n.s.), and the Hamilton rating scale for anxiety change scores were 7.8 for progesterone and 6.3 for placebo (F 0.22; df 2.30; n.s.). There was no difference in ability to remain drug-free at 12 weeks post-taper, with 57% of progesterone-treated patients, and 58% of placebo-treated patients having a successful outcome.

  7. Effect of mifepristone on steroid receptor expression and biotransformation of oestrogen and progesterone in rat uterus and deciduoma.

    Science.gov (United States)

    Vij, Urmila; Kumar, Anand; Sharma, Kanhaiya; Kaushal, Mishi; Mehra, Raj

    2006-01-01

    [corrected] Mifepristone is a synthetic antiprogestin which terminates early pregnancy. Since it interferes with the progesterone maintained decidua, we compared the effect of mifepristone on oestrogen and progesterone receptors, and on the biotransformation of these hormones in normal and deciduous uterus. Ovariectomized rats were treated with an oestrogen-progesterone hormone regimen and deciduoma was induced by trauma in one horn of the rat uterus while the other served as a control under an identical hormonal milieu. Hormone receptor and biotransformation studies were done using radiolabelled oestradiol and progesterone with high specific activity. The artificially formed decidual tissue was comparable with that of early pregnancy. Mifepristone replenished oestrogen and progesterone receptors which were suppressed by progesterone in both the normal and decidualized uterine horns. Inhibition of oestrogen receptors by progesterone correlated with decreased oestradiol levels at the site of action. Metabolism of progesterone to less potent compounds was promoted by mifepristone. The enzymatic activities of 17beta-hydroxysteroid dehydrogenase (which metabolizes oestradiol), and 20alpha-hydroxysteroid dehydrogenase and 5alpha-reductase (which metabolize progesterone) were altered by mifepristone. The effect of mifepristone in varying the hormone receptor population and the availability of different levels of active metabolites of ovarian hormones have an Important role in the antiprogestin action of mifepristone.

  8. Aldosterone and progesterone-secreting adrenocortical adenocarcinoma in a cat with a concurrent meningioma

    Directory of Open Access Journals (Sweden)

    Jana Leshinsky

    2016-01-01

    Full Text Available Case summary A 12-year-old, male neutered domestic shorthair cat was referred for investigation of suspected hyperaldosteronism due to persistent hypokalaemia, hindlimb ataxia, weakness of 1 month’s duration and a left adrenal mass that was detected on abdominal ultrasound. Neurological examination findings at referral were suggestive of a concurrent left forebrain lesion. Hyperaldosteronism and concurrent hyperprogesteronism were confirmed on endocrine testing. On computed tomography (CT of the abdomen and thorax there was no evidence of local vascular invasion by the adrenal mass or of metastatic disease. CT and magnetic resonance imaging featured a large, focal rim-enhancing extra-axial left forebrain lesion consistent with a meningioma. Surgical excision of the forebrain mass was followed by adrenalectomy 2 weeks later. The tumours were classified on histopathology as a psammomatous meningioma and an adrenocortical adenocarcinoma, respectively. Immunohistochemical staining of the meningioma confirmed the presence of progesterone receptors. The cat remains well 2 years later. Relevance and novel information In humans, elevated serum progesterone levels have been associated with rapid growth of meningiomas due to the presence of progesterone receptors on the tumour. This is the first report of a cat with a progesterone and aldosterone-secreting adrenocortical adenocarcinoma and a concurrent meningioma. Clinicians should be aware of the potential effect of elevated progesterone on meningiomas in cats.

  9. Unconventional endocannabinoid signaling governs sperm activation via the sex hormone progesterone.

    Science.gov (United States)

    Miller, Melissa R; Mannowetz, Nadja; Iavarone, Anthony T; Safavi, Rojin; Gracheva, Elena O; Smith, James F; Hill, Rose Z; Bautista, Diana M; Kirichok, Yuriy; Lishko, Polina V

    2016-04-29

    Steroids regulate cell proliferation, tissue development, and cell signaling via two pathways: a nuclear receptor mechanism and genome-independent signaling. Sperm activation, egg maturation, and steroid-induced anesthesia are executed via the latter pathway, the key components of which remain unknown. Here, we present characterization of the human sperm progesterone receptor that is conveyed by the orphan enzyme α/β hydrolase domain-containing protein 2 (ABHD2). We show that ABHD2 is highly expressed in spermatozoa, binds progesterone, and acts as a progesterone-dependent lipid hydrolase by depleting the endocannabinoid 2-arachidonoylglycerol (2AG) from plasma membrane. The 2AG inhibits the sperm calcium channel (CatSper), and its removal leads to calcium influx via CatSper and ensures sperm activation. This study reveals that progesterone-activated endocannabinoid depletion by ABHD2 is a general mechanism by which progesterone exerts its genome-independent action and primes sperm for fertilization. Copyright © 2016, American Association for the Advancement of Science.

  10. Comparative evaluation of ovarian structures in cattle by palpation per rectum, ultrasonography and plasma progesterone concentration.

    Science.gov (United States)

    Ribadu, A Y; Ward, W R; Dobson, H

    1994-11-05

    The aims of this study were to determine the relationship between the ultrasonographic determination of corpora lutea and the plasma progesterone profile of cyclic cows during an oestrous cycle, and to compare the accuracy of detection of normal and abnormal ovarian structures by ultrasonography and palpation per rectum, based on the plasma progesterone profile. The ovaries of six lactating cyclic dairy cows were scanned and blood samples were obtained three times a week for one month. There was a high correlation (r = 0.85) between the diameter of the corpus luteum and the plasma progesterone concentration, but on days -3 and -2 (oestrus = day 0) the diameter was the same as mid-luteal values but it was functionally inactive (plasma progesterone cows by using the plasma progesterone concentration and the dissection of ovaries post mortem as standards. The sensitivity, specificity and positive predictive value of palpation for identifying mid-cyclic corpora lutea were 85 per cent, 95.7 per cent and 89.5 per cent, respectively. Ultrasonography had a sensitivity of 95 per cent, a specificity of 100 per cent and a positive predictive value of 100 per cent. Twenty-nine cows were diagnosed by palpation per rectum as having either follicular or luteal cysts. During ultrasonography, an ovarian cyst was defined as a non-echogenic structure at least 5 mm in diameter.(ABSTRACT TRUNCATED AT 250 WORDS)

  11. Catch it before it kills: progesterone, obesity, and the prevention of endometrial cancer.

    Science.gov (United States)

    Carlson, Matthew J; Thiel, Kristina W; Yang, Shujie; Leslie, Kimberly K

    2012-09-01

    The lifetime risk for developing endometrial cancer, the fourth most common malignancy in women, is approximately 3%. Endometrial cancer is a hormone-driven cancer, with approximately 80% of endometrial cancers arising attributable to either an excess of estrogen or a lack of progesterone. In the normal endometrium, the proliferative effects of estrogen are normally countered by progesterone, but the absence of progesterone allows estrogen to induce oncogenesis, an effect that is amplified in situations of excess estrogen. One of the major emerging causes of the estrogen/progesterone imbalance is obesity. Obesity is associated with several hormonal derangements as well as dysregulation of insulin/insulin-like growth factor activity, which collectively contribute to hyperplasia and carcinogenesis in the endometrium. In this article, we provide an in-depth description of how obesity mechanistically promotes this hormone and growth factor imbalance. Given that endometrial cancer is clearly associated with obesity, we put forth the hypothesis that a large portion of these cancers might be prevented by treatment with progesterone.

  12. Women's attractiveness changes with estradiol and progesterone across the ovulatory cycle.

    Science.gov (United States)

    Puts, David A; Bailey, Drew H; Cárdenas, Rodrigo A; Burriss, Robert P; Welling, Lisa L M; Wheatley, John R; Dawood, Khytam

    2013-01-01

    In many species, females are more sexually attractive to males near ovulation. Some evidence suggests a similar pattern in humans, but methodological limitations prohibit firm conclusions at present, and information on physiological mechanisms underlying any such pattern is lacking. In 202 normally-cycling women, we explored whether women's attractiveness changed over the cycle as a function of two likely candidates for mediating these changes: estradiol and progesterone. We scheduled women to attend one session during the late follicular phase and another during the mid-luteal phase. At each session, facial photographs, voice recordings and saliva samples were collected. All photographs and voice recordings were subsequently rated by men for attractiveness and by women for flirtatiousness and attractiveness to men. Saliva samples were assayed for estradiol and progesterone. We found that progesterone and its interaction with estradiol negatively predicted vocal attractiveness and overall (facial plus vocal) attractiveness to men. Progesterone also negatively predicted women's facial attractiveness to men and female-rated facial attractiveness, facial flirtatiousness and vocal attractiveness, but not female-rated vocal flirtatiousness. These results strongly suggest a pattern of increased attractiveness during peak fertility in the menstrual cycle and implicate estradiol and progesterone in driving these changes. Copyright © 2012 Elsevier Inc. All rights reserved.

  13. Bioavailability and Fate of Sediment-Associated Progesterone in Aquatic Systems.

    Science.gov (United States)

    Sangster, Jodi L; Ali, Jonathan M; Snow, Daniel D; Kolok, Alan S; Bartelt-Hunt, Shannon L

    2016-04-05

    The environmental fate and bioavailability of progesterone, a steroid hormone known to cause endocrine-disrupting effects in aquatic organisms, is of growing concern due to its occurrence in the environment in water and sediment influenced by wastewater treatment plant and paper mill effluents, as well as livestock production. The objective of this study was to evaluate the fate of progesterone in two natural sediments and the corresponding alteration of gene expression in three steroid-responsive genes; vitellogenin, androgen receptor and estrogen receptor alpha. When exposed to progesterone-spiked sand, fathead minnows (Pimephales promelas) exhibited significant reductions in the expression of vitellogenin and androgen receptor expression. In contrast, fish exposed to progesterone associated with the silty loam sediment did not show a biological response at 7 days and only realized a significant reduction in vitellogenin. In both sediments, progesterone degradation resulted in the production of androgens including androsteinedione, testosterone, and androstadienedione, as well as the antiestrogen, testolactone. Differences in compound fate resulted in organism exposure to different suites of metabolites either in water or associated with the sediment. Results from this study suggest that environmental progestagens will lead to defeminization at environmentally relevant concentrations, and that exposure is influenced by sediment properties.

  14. The effect of unilateral progesterone infusion into the ovarian artery during the middle luteal phase on progesterone secretion in gilts.

    Science.gov (United States)

    Wasowska, Barbara; Stefańczyk-Krzymowska, Stanisława

    2009-03-01

    The aim of the study was to determine, in an experiment performed on conscious gilts, whether an increased amount of progesterone (P4) supplied to the porcine corpus luteum (CL), maintained within a physiological systemic concentration would influence its own secretion. On day 9 of the estrous cycle the jugular veins as well as both ovarian arteries and both ovarian veins were cannulated. In the experimental gilts (n=5), P4 was infused into the right ovarian arteries on days 10, 11 and 12 of the estrous cycle at a rate adequate for physiological retrograde transfer found during the middle luteal phase. The left ovarian arteries of these gilts were infused with saline. Both ovarian arteries of the control gilts (n=5) were infused with saline. The P4 infusion rate was 0.62 microg/min (10 day), 2 x 0.62 microg/min ( 11 day) and 3 x 0.62 microg/min (12 day) and physiological levels of the steroid were maintained. Blood samples were collected from the jugular vein and both ovarian veins in the experimental and control animals on days 10, 11 and 12 of the estrous cycle during two periods on each day: before and after P4 or saline infusion. The mean plasma P4 level in the ovarian vein ipsilateral to the P4-infused ovary was significantly (pgilts and in the ovarian vein of the control gilts. This was also true for day 12 of the estrous cycle (p0.05) among the particular days of the experiment. In contrast, mean P4 levels in the contralateral ovarian vein of the experimental gilts as well as in the ovarian vein of the control gilts tended to decrease (pfeedback between P4 being retrograde transferred into the ovary and P4 ovarian secretion.

  15. The metabolic clearance of progesterone in the pregnant rat: Absence of a physiological role for the lung

    Energy Technology Data Exchange (ETDEWEB)

    Waddell, B.J.; Bruce, N.W. (Univ. of Western Australia, Nedlands)

    1989-06-01

    The metabolic clearance rate (MCR) of progesterone is among the highest for all steroid hormones studied, yet it is difficult to apportion this high MCR to specific organ contributions. The isolated lung has been shown to metabolize progesterone, and since this tissue receives the entire cardiac output, potentially it could make a major contribution to the overall MCR. This possibility was examined in the present study by measuring lung extraction of (3H)progesterone under steady-state conditions in the intact pregnant rat. Anesthetized rats (n = 6) were infused with (3H)progesterone via a femoral vein for 100 min on Day 16 of pregnancy. After the onset of steady state (40 min), four blood samples were obtained at 20-min intervals from the right ventricle and from the aorta, and the concentrations of (3H)progesterone and its metabolites were determined. Throughout the sampling period, mean arterial pressure and heart rate remained stable (two-way analysis of variance), as did the production rate (3.76 +/- 0.35 mg/day; mean +/- SEM) and the MCR (34.8 +/- 3.5 ml/min) of progesterone. Despite this high rate of clearance, there was no difference between the concentration of (3H)progesterone in arterial and right ventricular blood, indicating no net extraction of progesterone during passage through the lung. Furthermore, there was no change in the concentration of either lipid-soluble or aqueous-soluble (3H)progesterone metabolites during trans-lung passage. These observations demonstrate that the lung does not contribute to the MCR of progesterone when measured under physiological and steady-state conditions. Therefore, the relationship, MCR (ml/min) = whole-body extraction (%) x cardiac output (ml/min), is upheld for progesterone in the rat.

  16. Mineralocorticoid receptor haplotype, estradiol, progesterone and emotional information processing.

    Science.gov (United States)

    Hamstra, Danielle A; de Kloet, E Ronald; Quataert, Ina; Jansen, Myrthe; Van der Does, Willem

    2017-02-01

    Carriers of MR-haplotype 1 and 3 (GA/CG; rs5522 and rs2070951) are more sensitive to the influence of oral contraceptives (OC) and menstrual cycle phase on emotional information processing than MR-haplotype 2 (CA) carriers. We investigated whether this effect is associated with estradiol (E2) and/or progesterone (P4) levels. Healthy MR-genotyped premenopausal women were tested twice in a counterbalanced design. Naturally cycling (NC) women were tested in the early-follicular and mid-luteal phase and OC-users during OC-intake and in the pill-free week. At both sessions E2 and P4 were assessed in saliva. Tests included implicit and explicit positive and negative affect, attentional blink accuracy, emotional memory, emotion recognition, and risky decision-making (gambling). MR-haplotype 2 homozygotes had higher implicit happiness scores than MR-haplotype 2 heterozygotes (p=0.031) and MR-haplotype 1/3 carriers (p<0.001). MR-haplotype 2 homozygotes also had longer reaction times to happy faces in an emotion recognition test than MR-haplotype 1/3 (p=0.001). Practice effects were observed for most measures. The pattern of correlations between information processing and P4 or E2 differed between sessions, as well as the moderating effects of the MR genotype. In the first session the MR-genotype moderated the influence of P4 on implicit anxiety (sr=-0.30; p=0.005): higher P4 was associated with reduction in implicit anxiety, but only in MR-haplotype 2 homozygotes (sr=-0.61; p=0.012). In the second session the MR-genotype moderated the influence of E2 on the recognition of facial expressions of happiness (sr=-0.21; p=0.035): only in MR-haplotype 1/3 higher E2 was correlated with happiness recognition (sr=0.29; p=0.005). In the second session higher E2 and P4 were negatively correlated with accuracy in lag2 trials of the attentional blink task (p<0.001). Thus NC women, compared to OC-users, performed worse on lag 2 trials (p=0.041). The higher implicit happiness scores of MR

  17. Structural Basis for Agonism and Antagonism for a Set of Chemically Related Progesterone Receptor Modulators

    Science.gov (United States)

    Lusher, Scott J.; Raaijmakers, Hans C. A.; Vu-Pham, Diep; Dechering, Koen; Lam, Tsang Wai; Brown, Angus R.; Hamilton, Niall M.; Nimz, Olaf; Bosch, Rolien; McGuire, Ross; Oubrie, Arthur; de Vlieg, Jacob

    2011-01-01

    The progesterone receptor is able to bind to a large number and variety of ligands that elicit a broad range of transcriptional responses ranging from full agonism to full antagonism and numerous mixed profiles inbetween. We describe here two new progesterone receptor ligand binding domain x-ray structures bound to compounds from a structurally related but functionally divergent series, which show different binding modes corresponding to their agonistic or antagonistic nature. In addition, we present a third progesterone receptor ligand binding domain dimer bound to an agonist in monomer A and an antagonist in monomer B, which display binding modes in agreement with the earlier observation that agonists and antagonists from this series adopt different binding modes. PMID:21849509

  18. Progesterone receptor content in endometrial carcinoma correlates with serum levels of free estradiol

    DEFF Research Database (Denmark)

    Nyholm, H C; Nielsen, Anette Lynge; Lyndrup, J

    1993-01-01

    between estrogen receptor content and any of the serum sex hormones. The progesterone/estrogen receptor ratio, calculated from the biochemical values, correlated positively (p levels of free estradiol. This relation was not affected by tumor histologic grade or stage. Furthermore......OBJECTIVE. To study a possible relationship between serum levels of estrogens and androgens and the tumor content of estrogen receptors and progesterone receptors in endometrial cancer. STUDY DESIGN. Fifty postmenopausal patients were included. Receptors were determined biochemically in tissue...... cytosol by dextran charcoal-coated assay and immunohistochemically on frozen sections. Serum sex hormones were measured by radioimmunoassays. MAIN FINDINGS. Tumor biochemical progesterone receptor content correlated positively (p levels. No correlations were observed...

  19. [Cyclic concentration of estradiol and progesterone in hysterectomized women (author's transl)].

    Science.gov (United States)

    Reynoso Ron, L; Aznar Ramos, R; Bedolla Tovar, N; Cortés-Gallegos, V

    1975-01-01

    The cyclic concentration of estradiol and progesterone was studied in 6 women, 30 years of age or less, who underwent hysterectomy, 7 to 14 months earlier, because of obstetrical complications. The basal body temperature curve, as well as the daily concentrations of plasma estradiol and progesterone during one cycle, showed a pattern similar to that of the control group, except for 2 women with a luteal phase of 16 days, who had progesterone levels of 5 ng/ml or more. Although these values are indicative of ovulation, they fell in the lower limit of the range considered as ovulatory in the laboratory that conducted the test. It is concluded that hysterectomy, with the interruption of the circulation of the ovaric branch of the uterine artery, does not affect the normal esteroidogenic function of the ovary.

  20. Detection of oestrogen and progesterone receptor expression in breast tumors by semiquantitative PCR.

    Science.gov (United States)

    Hackl, T; Zickl, M; Dobianer, K; Hruza, C; Czerwenka, K; Spona, J

    1998-01-01

    Estimation of oestrogen receptors (ER) and progesterone receptors (PgR) by dextran-coated charcoal (DCC) or immunohistochemical methods have become standard practices in the management of breast cancer. A "multiplex" polymerase chain reaction (PCR) system was developed for quantitative estimation of ER and PgR mRNA in breast tumour specimens. A statistically significant correlation could be found between the mRNA of the oestrogen and the progesterone receptor (p < or = 0.0001). Protein data defined in classes, compared with mRNA data showed a significant correlation for the oestrogen receptor (p < or = 0.0001) as well as for the progesterone receptor (p < or = 0.046). Messenger RNA could be determined by the present PCR system in tumours assayed as negative by DCC method. Therefore, this sensitive PCR procedure, which requires small amounts of material may be very useful as a diagnostic test to determine the choice of therapy.

  1. Preovulatory progesterone concentration associates significantly to follicle number and LH concentration but not to pregnancy rate

    DEFF Research Database (Denmark)

    Yding Andersen, Claus; Bungum, Leif; Nyboe Andersen, Anders

    2011-01-01

    Using data from a large prospective randomized controlled trial that evaluated the effect of recombinant LH (rLH)co-administration for ovarian stimulation, the present study assessed whether progesterone concentration on the day of human chorionic gonadotrophin (HCG) administration was associated...... with pregnancy outcome. Progesterone concentration was measured on stimulation day 1 and on the day of HCG administration in 475 patients who underwent IVF/intracytoplasmic sperm injection treatment following ovarian stimulation with gonadotrophin-releasing hormone (GnRH) agonist and recombinant FSH...... of HCG administration and the probability of clinical pregnancy in women undergoing ovarian stimulation with GnRH agonists and gonadotrophins for assisted reproduction treatment.Instead, late-follicular-phase progesterone concentration appears to be governed by the number of preovulatory follicles and LH...

  2. Temporary undernutrition during early gestation, corpora lutea morphometrics, ovarian progesterone secretion and embryo survival in gilts.

    Science.gov (United States)

    Langendijk, P; Bouwman, E G; Chen, T Y; Koopmanschap, R E; Soede, N M

    2017-07-01

    The present study reports effects of severe undernutrition on luteal function and pregnancy in pigs. Gilts were inseminated and either fasted on Day 10 and 11 after conception (n=11) or fully fed throughout (n=10). Fasting did not affect LH or progesterone pulsatile secretion pattern on Day 11 in samples taken from blood vessels draining an ovary. Ultrasonographic measurements of the size of the corpora lutea did not show any effect of fasting either. However, fasted gilts had 10 to 30% lower systemic progesterone from Day 12 through Day 15 after conception (Pgilts farrowed, but fasted gilts had fewer born piglets than fully fed gilts (8.8±0.8 vs 10.9±0.5 respectively; P<0.05). In conclusion, fasting during embryo elongation can compromise embryonic survival by affecting ovarian function in the days after fasting, without having an immediate effect on LH secretion and progesterone output by the ovaries.

  3. Pengaruh medroksi progesteron asetat terhadap ultrastruktur sel leydig tikus putih (Rattus norvegicus

    Directory of Open Access Journals (Sweden)

    Mahanani Tri Asri

    1999-12-01

    Full Text Available The objective of the research was to study the effect of medroxy progesterone acetate on the ultrastructure of Leydig cells of Rattus norvegicus. Randomized complete design was applied to study. Treatment consisted of 4 doses medroxy progesterone acetate were 0.4. 8. And 12 mg per rat respectively and 8 replications. Injection were applied perform 4 times per rat within 4 weeks interval. The testicle were examined ultrastructure change on the nucleus, endoplasmic reticulum, mitochondria and golgy apparatus of the Leydig cells. Results indicated that injections of medroxy progesterone acetate of 8 and 12 mg per rat causes significant untrastructure change of nucleus, endoplasmic reticulum, golgy apparatus and mitocondria of Leydig cells in comparison with doses 0 and 4 mg per rat. In additions there were no significant different in ultrastructure of Leydig cells between doses 8 and 12 mg per rat as well as there were no significant different between doses of 4 and 0 mg per rat.

  4. Microarray Analysis on Gene Regulation by Estrogen, Progesterone and Tamoxifen in Human Endometrial Stromal Cells

    Directory of Open Access Journals (Sweden)

    Chun-E Ren

    2015-03-01

    Full Text Available Epithelial stromal cells represent a major cellular component of human uterine endometrium that is subject to tight hormonal regulation. Through cell-cell contacts and/or paracrine mechanisms, stromal cells play a significant role in the malignant transformation of epithelial cells. We isolated stromal cells from normal human endometrium and investigated the morphological and transcriptional changes induced by estrogen, progesterone and tamoxifen. We demonstrated that stromal cells express appreciable levels of estrogen and progesterone receptors and undergo different morphological changes upon hormonal stimulation. Microarray analysis indicated that both estrogen and progesterone induced dramatic alterations in a variety of genes associated with cell structure, transcription, cell cycle, and signaling. However, divergent patterns of changes, and in some genes opposite effects, were observed for the two hormones. A large number of genes are identified as novel targets for hormonal regulation. These hormone-responsive genes may be involved in normal uterine function and the development of endometrial malignancies.

  5. Selectivity in progesterone and androgen receptor binding of progestagens used in oral contraceptives

    Energy Technology Data Exchange (ETDEWEB)

    Kloosterboer, H.J.; Vonk-Noordegraaf, C.A.; Turpijn, E.W.

    1988-09-01

    The relative binding affinities (RBAs) of four progestational compounds (norethisterone, levonorgestrel, 3-keto-desogestrel and gestodene) for the human progesterone and androgen receptors were measured in MCF-7 cytosol and intact MCF-7 cells. For the binding to the progesterone receptor, both Org 2058 and Org 3236 (or 3-keto-desogestrel) were used as labelled ligands. The following ranking (low to high) for the RBA of the nuclear (intact cells) progesterone receptor irrespective of the ligand used is found: norethisterone much less than levonorgestrel less than 3-keto-destogestrel less than gestodene. The difference between the various progestagens is significant with the exception of that between 3-keto-desogestrel and gestodene, when Org 2058 is used as ligand. For the cytosolic progesterone receptor, the same order is found with the exception that similar RBAs are found for gestodene and 3-keto-desogestrel. The four progestagens clearly differ with respect to binding to the androgen receptor using dihydrotestosterone as labelled ligand in intact cells; the ranking (low to high) is: norethisterone less than 3 keto-desogestrel less than levonorgestrel and gestodene. The difference between 3-keto-desogestrel and levonorgestrel or gestodene is significant. The selectivity indices (ratio of the mean RBA for the progesterone receptor to that of androgen receptor) in intact cells are significantly higher for 3-keto-desogestrel and gestodene than for levonorgestrel and norethisterone. From these results we conclude that the introduction of the 18-methyl in norethisterone (levonorgestel) increases both the binding to the progesterone and androgen receptors.

  6. Concentrations of estrogen and progesterone in breast milk and their relationship with the mother's diet.

    Science.gov (United States)

    Lu, Mengqing; Xiao, Hailong; Li, Kelei; Jiang, Jiajing; Wu, Kejian; Li, Duo

    2017-09-20

    The aim of the present study was to determine the concentrations of estradiol (E2), estriol (E3) and progesterone in breast milk over different lactation periods, and to assess their relationship with the mother's diet. Ninety-six breast milk samples as well as 24-hour dietary records from 32 lactating mothers were collected on day 1 (colostrum), day 14 (transitional milk) and day 42 (mature milk) after delivery in Hangzhou, China. The concentrations of E2, E3 and progesterone differed significantly through different periods of lactation (p milk and mature milk was 1.60 ± 0.96 μg L -1 , 0.83 ± 0.36 μg L -1 and 1.26 ± 0.48 μg L -1 , respectively. The concentrations of E3 were 2.09 ± 1.66 μg L -1 , 2.23 ± 1.74 μg L -1 and 4.64 ± 2.15 μg L -1 , respectively. The concentrations of progesterone were 6.10 ± 8.30 μg L -1 , 4.25 ± 4.76 μg L -1 and 1.70 ± 2.42 μg L -1 , respectively. The concentration of progesterone in breast milk was significantly negatively correlated with the intake of protein (p = 0.015), fat (p = 0.008), vegetables (p = 0.012), and meat and eggs (p = 0.036), while the concentration of E3 was significantly positively correlated with the intake of soy products (p = 0.025). This information indicates that the concentrations of E2, E3 and progesterone in breast milk varied over the lactating period. Dietary intake will to some extent affect the contents of E3 and progesterone in breast milk.

  7. Evaluation of oestrus observation and conception rates in suckling beef cows using whole milk progesterone concentration

    Directory of Open Access Journals (Sweden)

    D.C. Lourens

    2002-07-01

    Full Text Available A 2-sample regime was used to measure whole milk progesterone concentration on the day of oestrus and insemination (Day 0 and 6 days later (Day 6 in a sample of 50 primiparous and 100 multiparous suckling beef cows. Exposure to teaser bulls and observation by cattlemen identified the occurrence of oestrus. Three sets of criteria used to define ovulatory oestrus were compared : a milk progesterone concentration less than 6 nmol / l on Day 0 ; b milk progesterone less than 6 nmol / l on Day 0 and rising to greater than 6 nmol / l on Day 6; c milk progesterone less than 6 nmol / l on Day 0 and rising to greater than 6 nmol / l on Day 6, or cow diagnosed pregnant to 1st insemination. Using only a single milk sample on Day 0 (criterion a would have resulted in the positive predictive value of heat detection being estimated at 98.7%. Using a paired measurement (criterion b resulted in a significantly lower estimate of 84.7%. The inclusion of cows that conceived despite not showing a marked rise in milk progesterone concentration (criterion c resulted in a more accurate estimate of 89.3%. Use of a 2-sample regime also allowed calculation of conception rates while eliminating the effect of heat detection errors. In the cows sampled, of those in ovulatory oestrus that were inseminated, 73.1% conceived to the 1st insemination. These results demonstrate that artificial insemination within a limited breeding season can be successful if nutrition is optimal and management is intensive. The use of a 2-sample milk progesterone test may be a valuable tool in investigating heat detection and conception problems in beef herds in which artificial insemination is used.

  8. TBI and sex: crucial role of progesterone protecting the brain in an omega-3 deficient condition.

    Science.gov (United States)

    Tyagi, Ethika; Agrawal, Rahul; Ying, Zhe; Gomez-Pinilla, Fernando

    2014-03-01

    We assessed whether the protective action of progesterone on traumatic brain injury (TBI) could be influenced by the consumption of omega-3 fatty acids during early life. Pregnant Sprague-Dawley rats were fed on omega-3 adequate or deficient diet from 3rd day of pregnancy and their female offspring were kept on the same diets up to the age of 15 weeks. Ovariectomy was performed at the age of 12 weeks to deprive animals from endogenous steroids until the time of a fluid percussion injury (FPI). Dietary n-3 fatty acid deficiency increased anxiety in sham animals and TBI aggravated the effects of the deficiency. Progesterone replacement counteracted the effects of TBI on the animals reared under n-3 deficiency. A similar pattern was observed for markers of membrane homeostasis such as 4-Hydroxynonenal (HNE) and secreted phospholipases A2 (sPLA2), synaptic plasticity such as brain derived neurotrophic factor (BDNF), syntaxin (STX)-3 and growth associated protein (GAP)-43, and for growth inhibitory molecules such as myelin-associated glycoprotein (MAG) and Nogo-A. Results that progesterone had no effects on sham n-3 deficient animals suggest that the availability of progesterone is essential under injury conditions. Progesterone treatment counteracted several parameters related to synaptic plasticity and membrane stability reduced by FPI and n-3 deficiency suggest potential targets for therapeutic applications. These results reveal the importance of n-3 preconditioning during early life and the efficacy of progesterone therapy during adulthood to counteract weaknesses in neuronal and behavioral plasticity. Copyright © 2014 Elsevier Inc. All rights reserved.

  9. Behavioral effects of endogenous or exogenous estradiol and progesterone on cocaine sensitization in female rats

    Energy Technology Data Exchange (ETDEWEB)

    Souza, M.F. [Universidade Federal de Ciências da Saúde de Porto Alegre, Laboratório de Neurociência Comportamental, Porto Alegre, RS, Brasil, Laboratório de Neurociência Comportamental, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, RS (Brazil); Couto-Pereira, N.S. [Universidade Federal do Rio Grande do Sul, Instituto de Ciências Básicas da Saúde, Departamento de Bioquímica, Porto Alegre, RS, Brasil, Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS (Brazil); Freese, L.; Costa, P.A.; Caletti, G.; Bisognin, K.M. [Universidade Federal de Ciências da Saúde de Porto Alegre, Laboratório de Neurociência Comportamental, Porto Alegre, RS, Brasil, Laboratório de Neurociência Comportamental, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, RS (Brazil); Nin, M.S. [Universidade Federal de Ciências da Saúde de Porto Alegre, Laboratório de Neurociência Comportamental, Porto Alegre, RS, Brasil, Laboratório de Neurociência Comportamental, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, RS (Brazil); Instituto Porto Alegre, Centro Metodista do Sul, Curso de Farmácia, Porto Alegre, RS, Brasil, Curso de Farmácia, Centro Metodista do Sul, Instituto Porto Alegre, Porto Alegre, RS (Brazil); Gomez, R. [Universidade Federal do Rio Grande do Sul, Instituto de Ciências Básicas da Saúde, Departamento de Farmacologia, Porto Alegre, RS, Brasil, Departamento de Farmacologia, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS (Brazil); Barros, H.M.T. [Universidade Federal de Ciências da Saúde de Porto Alegre, Laboratório de Neurociência Comportamental, Porto Alegre, RS, Brasil, Laboratório de Neurociência Comportamental, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, RS (Brazil)

    2014-05-09

    Cocaine sensitization is a marker for some facets of addiction, is greater in female rats, and may be influenced by their sex hormones. We compared the modulatory effects of endogenous or exogenous estradiol and progesterone on cocaine-induced behavioral sensitization in 106 female rats. Ovariectomized female rats received progesterone (0.5 mg/mL), estradiol (0.05 mg/mL), progesterone plus estradiol, or the oil vehicle. Sham-operated control females received oil. Control and acute subgroups received injections of saline, while the repeated group received cocaine (15 mg/kg, ip) for 8 days. After 10 days, the acute and repeated groups received a challenge dose of cocaine, after which locomotion and stereotypy were monitored. The estrous cycle phase was evaluated and blood was collected to verify hormone levels. Repeated cocaine treatment induced overall behavioral sensitization in female rats, with increased locomotion and stereotypies. In detailed analysis, ovariectomized rats showed no locomotor sensitization; however, the sensitization of stereotypies was maintained. Only females with endogenous estradiol and progesterone demonstrated increased locomotor activity after cocaine challenge. Estradiol replacement enhanced stereotyped behaviors after repeated cocaine administration. Cocaine sensitization of stereotyped behaviors in female rats was reduced after progesterone replacement, either alone or concomitant with estradiol. The behavioral responses (locomotion and stereotypy) to cocaine were affected differently, depending on whether the female hormones were of an endogenous or exogenous origin. Therefore, hormonal cycling appears to be an important factor in the sensitization of females. Although estradiol increases the risk of cocaine sensitization, progesterone warrants further study as a pharmacological treatment in the prevention of psychostimulant abuse.

  10. Progesterone Induces Mucosal Immunity in a Rodent Model of Human Taeniosis by Taenia solium

    Science.gov (United States)

    Escobedo, Galileo; Camacho-Arroyo, Ignacio; Nava-Luna, Paul; Olivos, Alfonso; Pérez-Torres, Armando; Leon-Cabrera, Sonia; Carrero, J.C.; Morales-Montor, Jorge

    2011-01-01

    More than one quarter of human world's population is exposed to intestinal helminth parasites. The Taenia solium tapeworm carrier is the main risk factor in the transmission of both human neurocysticercosis and porcine cysticercosis. Sex steroids play an important role during T. solium infection, particularly progesterone has been proposed as a key immunomodulatory hormone involved in susceptibility to human taeniosis in woman and cysticercosis in pregnant pigs. Thus, we evaluated the effect of progesterone administration upon the experimental taeniosis in golden hamsters (Mesocricetus auratus). Intact female adult hamsters were randomly divided into 3 groups: progesterone-subcutaneously treated; olive oil-treated as the vehicle group; and untreated controls. Animals were treated every other day during 4 weeks. After 2 weeks of treatment, all hamsters were orally infected with 4 viable T. solium cysticerci. After 2 weeks post infection, progesterone-treated hamsters showed reduction in adult worm recovery by 80%, compared to both vehicle-treated and non-manipulated infected animals. In contrast to control and vehicle groups, progesterone treatment diminished tapeworm length by 75% and increased proliferation rate of leukocytes from spleen and mesenteric lymph nodes of infected hamsters by 5-fold. The latter exhibited high expression levels of IL-4, IL-6 and TNF-α at the duodenal mucosa, accompanied with polymorphonuclear leukocytes infiltration. These results support that progesterone protects hamsters from the T. solium adult tapeworm establishment by improving the intestinal mucosal immunity, suggesting a potential use of analogues of this hormone as novel inductors of the gut immune response against intestinal helminth infections and probably other bowel-related disorders. PMID:22110394

  11. Study on prevention effect of Zishen Yutai pill combined with progesterone for threatened abortion in rats.

    Science.gov (United States)

    Zhang, Yi; Yan, Wei; Ge, Pu-Feng; Li, Yan; Ye, Qian

    2016-06-01

    To observe preventive and therapeutic effects and the mechanism of actions on Zishen Yutai pill combined with progesterone on threatened abortion in rats. After pregnancy, 50 SPF female SD rats were selected and divided into control group, model group, progesterone group, Zishen Yutai pill group, and progesterone plus Zishen Yutai pill group (combination group), with 10 rats in each group. The rats of control group and abortion model group were lavaged with 2 mL/kg normal saline on pregnancy day 1 for continuous 10 days. Rats in Zishen Yutai pill group were given 1.575 g/kg/d of Zishen Yutai pill for intragastric administration for continuous 10 days. Rats in progesterone group were given intramuscular injection treatment of 0.1 mL/d progestin, continuous for 10 days. Rats in combination group were given injection therapy of aqueous solution of Zishen Yutai pill for continuous 10 days, and other treatments were the same as previous two groups. Abortion model were established then and live births, numbers of abortion and average rate of abortion were compared between the five groups. Peripheral blood was collected to detect the estradiol (E2) and progestational hormone (P), and obtain ratio of Th1/Th2 cytokines (IL-2, INF-γ, IL-4, IL-10). Significant more live births of rats were found in the control group compared with other four groups (P pill group and joint group (P pill group. The serum E2 level of P of rats in the control group, progesterone group, Zishen Yutai pill group and joint group were significant higher than that of abortion model group (P pill group and joint group were not significant different (P > 0.05) but these levels in the control group and Zishen Yutai pill group were significant lower than that of progesterone group and joint group (P pill group and joint group were balanced deviating to Th2, and joint group' deviation was better than progesterone group and Zishen Yutai pill group (P pill combined with progesterone has a

  12. A paracrine role for the epithelial progesterone receptor in mammary gland development

    OpenAIRE

    Brisken, Cathrin; Park, Sissela; Vass, Tibor; Lydon, John P.; O’Malley, Bert W.; Weinberg, Robert A.

    1998-01-01

    Recently generated progesterone receptor (PR)-negative (PR−/−) mice provide an excellent model for dissecting the role of progesterone in the development of the mammary gland during puberty and pregnancy. However, the full extent of the mammary gland defect in these mice caused by the absence of the PR cannot be assessed, because PR−/− mice do not exhibit estrous cycles and fail to become pregnant. To circumvent this difficulty, we have transplanted PR−/− breasts into wild-type mice, and we h...

  13. Progesterone reduces erectile dysfunction in sleep-deprived spontaneously hypertensive rats

    Directory of Open Access Journals (Sweden)

    Tufik Sergio

    2007-03-01

    Full Text Available Abstract Background Paradoxical sleep deprivation (PSD associated with cocaine has been shown to enhance genital reflexes (penile erection-PE and ejaculation-EJ in Wistar rats. Since hypertension predisposes males to erectile dysfunction, the aim of the present study was to investigate the effects of PSD on genital reflexes in the spontaneously hypertensive rat (SHR compared to the Wistar strain. We also extended our study to examine how PSD affect steroid hormone concentrations involved in genital events in both experimental models. Methods The first experiment investigated the effects of PSD on genital reflexes of Wistar and SHR rats challenged by saline and cocaine (n = 10/group. To further examine the impact of the PSD on concentrations of sexual hormones, we performed a hormonal analysis of testosterone and progesterone in the Wistar and in SHR strains. Since after PSD progesterone concentrations decreased in the SHR compared to the Wistar PSD group we extended our study by investigating whether progesterone (25 mg/kg or 50 mg/kg or testosterone (0.5 mg/kg or 1.0 mg/kg administration during PSD would have a facilitator effect on the occurrence of genital reflexes in this hypertensive strain. Results A 4-day period of PSD induced PE in 50% of the Wistar rats against 10% for the SHR. These genital reflexes was potentiated by cocaine in Wistar rats whereas this scenario did not promote significant enhancement in PE and EJ in hypertensive rats, and the percentage of SHR displaying genital reflexes still figured significantly lower than that of the Wistar strain. As for hormone concentrations, both sleep-deprived Wistar and SHR showed lower testosterone concentrations than their respective controls. Sleep deprivation promoted an increase in concentrations of progesterone in Wistar rats, whereas no significant alterations were found after PSD in the SHR strain, which did not present enhancement in erectile responses. In order to explore the role

  14. BfR does not see any association between progesterone levels in milk and breast cancer

    OpenAIRE

    Federal Institute for Risk Assessment

    2008-01-01

    The Federal Institute for Risk Assessment (BfR) expresses its opinion on a possible associa-tion between rising milk consumption and the onset of cancer. In particular breast and pros-tate cancer are said to be attributable to the increased consumption of milk and dairy prod-ucts. The reasons given are the natural, hormonal ingredients in milk. Besides carbohy-drates, proteins, vitamins and trace elements, milk also contains hormones like, for instance, progesteroneProgesterone is a fem...

  15. Role of Cervical Cerclage and Vaginal Progesterone in the Treatment of Cervical Incompetence with/without Preterm Birth History

    Directory of Open Access Journals (Sweden)

    Shao-Wei Wang

    2016-01-01

    Conclusions: Cervical cerclage showed more benefits in the maternal and neonatal outcomes than vaginal progesterone therapy for women with an asymptomatic short cervix and prior PTB history, while cervical cerclage and vaginal progesterone therapies showed similar effectiveness for women with an asymptomatic short cervix but without a history of PTB.

  16. Finasteride inhibits the progesterone-induced spike-wave discharges in a genetic model of absence epilepsy

    NARCIS (Netherlands)

    Luijtelaar, E.L.J.M. van; Budziszewska, B.; Tetich, M.; Lason, W.

    2003-01-01

    Previously, it was found that progesterone aggravates spike-wave discharges (SWD) in WAG/Rij rats in a nongenomic way. In order to elucidate whether the regulatory effect of progesterone depends on its conversion to allopregnanolone, the effect of finasteride, a 5alpha-reductase inhibitor, on

  17. Effects of progesterone and vitamin D on outcome of patients with acute traumatic spinal cord injury; a randomized, double-blind, placebo controlled study

    National Research Council Canada - National Science Library

    Aminmansour, Bahram; Asnaashari, Ali; Rezvani, Majid; Ghaffarpasand, Fariborz; Amin Noorian, Seyed Mohammad; Saboori, Masih; Abdollahzadeh, Parisa

    2016-01-01

    ...) while the role of progesterone and vitamin D remain controversial. The aim of the current study was to investigate the effects of progesterone and vitamin D on functional outcome of patients with acute traumatic SCI...

  18. Comparison of the administration of progesterone versus progesterone and vitamin D in improvement of outcomes in patients with traumatic brain injury: A randomized clinical trial with placebo group

    OpenAIRE

    Bahram Aminmansour; Hossein Nikbakht; Abbas Ghorbani; Majid Rezvani; Paiman Rahmani; Mostaffa Torkashvand; Mohammadamin Nourian; Mehran Moradi

    2012-01-01

    Background: Due to the heterogeneity of traumatic brain injury (TBI), many of single treatments have not been successful in prevention and cure of these kinds of injuries. The neuroprotective effect of progesterone drug on severe brain injuries has been identified, and recently, the neuroprotective effect of vitamin D has also been studied as the combination of these two drugs has shown better effects on animal samples in some studies. This study was conducted to examine the effect of vitamin...

  19. Loss of progesterone receptor-mediated actions induce preterm cellular and structural remodeling of the cervix and premature birth.

    Directory of Open Access Journals (Sweden)

    Steven M Yellon

    Full Text Available A decline in serum progesterone or antagonism of progesterone receptor function results in preterm labor and birth. Whether characteristics of premature remodeling of the cervix after antiprogestins or ovariectomy are similar to that at term was the focus of the present study. Groups of pregnant rats were treated with vehicle, a progesterone receptor antagonist (onapristone or mifepristone, or ovariectomized on day 17 postbreeding. As expected, controls given vehicle delivered at term while rats delivered preterm after progesterone receptor antagonist treatment or ovariectomy. Similar to the cervix before term, the preterm cervix of progesterone receptor antagonist-treated rats was characterized by reduced cell nuclei density, decreased collagen content and structure, as well as a greater presence of macrophages per unit area. Thus, loss of nuclear progesterone receptor-mediated actions promoted structural remodeling of the cervix, increased census of resident macrophages, and preterm birth much like that found in the cervix at term. In contrast to the progesterone receptor antagonist-induced advance in characteristics associated with remodeling, ovariectomy-induced loss of systemic progesterone did not affect hypertrophy, extracellular collagen, or macrophage numbers in the cervix. Thus, the structure and macrophage census in the cervix appear sufficient for premature ripening and birth to occur well before term. With progesterone receptors predominantly localized on cells other than macrophages, the findings suggest that interactions between cells may facilitate the loss of progesterone receptor-mediated actions as part of a final common mechanism that remodels the cervix in certain etiologies of preterm and with parturition at term.

  20. Micro-dose hCG as luteal phase support without exogenous progesterone administration

    DEFF Research Database (Denmark)

    Andersen, C Yding; Fischer, R; Giorgione, V

    2016-01-01

    For the last two decades, exogenous progesterone administration has been used as luteal phase support (LPS) in connection with controlled ovarian stimulation combined with use of the human chorionic gonadotropin (hCG) trigger for the final maturation of follicles. The introduction of the GnRHa tr...

  1. Preovulatory progesterone concentration associates significantly to follicle number and LH concentration but not to pregnancy rate

    DEFF Research Database (Denmark)

    Yding Andersen, Claus; Bungum, Leif; Nyboe Andersen, Anders

    2011-01-01

    of HCG administration and the probability of clinical pregnancy in women undergoing ovarian stimulation with GnRH agonists and gonadotrophins for assisted reproduction treatment.Instead, late-follicular-phase progesterone concentration appears to be governed by the number of preovulatory follicles and LH...

  2. Endogenous progesterone and its cellular binding sites in wheat exposed to drought stress

    Czech Academy of Sciences Publication Activity Database

    Janeczko, A.; Oklešťková, Jana; Siwek, A.; Dziurka, M.; Pociecha, E.; Kocurek, M.; Novák, Ondřej

    2013-01-01

    Roč. 138, č. 2013 (2013), s. 384-394 ISSN 0960-0760 R&D Projects: GA MŠk LK21306 Institutional research plan: CEZ:AV0Z50380511 Keywords : Plants * Wheat * Progesterone Subject RIV: EF - Botanics Impact factor: 4.049, year: 2013

  3. Reproductive responses and progesterone levels of postpartum oestrus synchronization in goats with different body reserves

    Directory of Open Access Journals (Sweden)

    Fabiana V. Rodrigues

    2011-10-01

    Full Text Available Thirty adult goats were classified at parturition into two body condition score (BCS groups: BCI (n=16 with a score of 2.7 and BCII (n=14 with a score of 2.0. On the fiftieth day postpartum, oestrus was synchronized by CIDR for 5 days. Upon CIDR removal (Day 0, they received 1 mL of PGF2α IM and mated for 72 hours. Kids were kept with does and weaned at 40 days of age. Blood samples were taken at 0, 1, 4, 8 and 21 days after CIDR removal for progesterone assay. The BCI group showed a greater weight loss compared to the BCII group, and BCS before synchronization was 1.9±0.08 and 1.6±0.07 for the BCI and BCII groups, respectively (Pvs 36%; Pvs 1.25; Pvs 0.25; P<0.05. Progesterone concentration was higher in pregnant does in BCI. A positive relationship was found between progesterone level at CIDR removal and BCS at parturition (0.57; P<0.01, also between progesterone level at 21 days after CIDR removal and BCS at parturition (0.47; P<0.05, or BCS before synchronization (0.51; P<0.05. We conclude that oestrus response to postpartum CIDR synchronization appeared to be slightly dependent on BCS. However, goats with low BCS at oestrus synchronization exhibited a reduction in pregnancy rate.

  4. Dielectric relaxation and crystallization of ultraviscous melt and glassy states of aspirin, ibuprofen, progesterone, and quinidine.

    Science.gov (United States)

    Johari, G P; Kim, S; Shanker, Ravi M

    2007-05-01

    Molecular relaxation in ultraviscous melt and glassy states of aspirin, ibuprofen, progesterone, and quinidine has been studied by dielectric spectroscopy. The asymmetric relaxation spectra is characterized by the Kohlrausch distribution parameter of 0.46 +/- 0.02 for aspirin to 0.67 +/- 0.02 for progesterone. The dielectric relaxation time varies with the temperature, T, according to the Vogel-Fulcher-Tammann Equation, log(10)(tau(0)) = A(VFT) + [B(VFT)/(T - T(0))], where A(VFT), B(VFT), and T(0) are empirical constants. The extrapolated tau(0) at calorimetric glass-softening temperature is close to the value expected. The equilibrium permittivity, epsilon(0), is lowest for ibuprofen which indicates an antiparallel orientation of dipoles in its liquid's hydrogen-bonded structure. A decrease in epsilon(0) with time shows that ultraviscous aspirin, progesterone, and quinidine begin to cold-crystallize at a relatively lower temperature than ibuprofen. epsilon(0) of the cold-crystallized phases are, 4.7 for aspirin at 290 K, 2.55 for ibuprofen at 287 K, 2.6 for progesterone at 320 K, and 3.2 for quinidine at 375 K. It is argued that hydrogen-bonding, the Kohlrausch parameter, extent of localized motions and the long-range diffusion times all determine the physical and chemical stability of an amorphous pharmaceutical during storage. (c) 2007 Wiley-Liss, Inc. and the American Pharmacists Association.

  5. Combining Cattle Activity and Progesterone Measurements Using Hidden Semi-Markov Models

    DEFF Research Database (Denmark)

    O'Connell, Jared Michael; Tøgersen, Frede Aakmann; Friggens, Nic

    2011-01-01

    Hourly pedometer counts and irregularly measured concentration of the hormone progesterone were available for a large number of dairy cattle. A hidden semi-Markov was applied to this bivariate time-series data for the purposes of monitoring the reproductive status of cattle. In particular, the ab...

  6. Estimating genetic parameters for fertility in dairy cows from in-line milk progesterone profiles

    NARCIS (Netherlands)

    Tenghe, A.M.M.; Bouwman, A.C.; Berglund, B.; Strandberg, E.; Blom, J.; Veerkamp, R.F.

    2015-01-01

    The aim of this study was to define endocrine fertility traits from in-line milk progesterone (P4) records and to estimate genetic parameters for these traits. Correlations of classical fertility (calving interval and calving to first service) and milk production traits with endocrine fertility

  7. Genetic analysis of atypical progesterone profiles in Holstein-Friesian cows from experimental research herds

    NARCIS (Netherlands)

    Nyman, S.; Johansson, K.; Koning, de C.J.A.M.; Berry, D.P.; Veerkamp, R.F.; Wall, E.; Berglund, B.

    2014-01-01

    The objective of this study was to quantify the genetic variation in normal and atypical progesterone profiles and investigate if this information could be useful in an improved genetic evaluation for fertility for dairy cows. The phenotypes derived from normal profiles included cycle length traits,

  8. Progesterone and Related Compounds in Hepatocellular Carcinoma: Basic and Clinical Aspects

    Directory of Open Access Journals (Sweden)

    Yao-Tsung Yeh

    2013-01-01

    Full Text Available Primary liver cancer is the fifth most common cancer worldwide and the third most common cause of cancer mortality. Hepatocellular carcinoma (HCC accounts for 85% to 90% of primary liver cancers. Major risk factors for HCC include infection with HBV or HCV, alcoholic liver disease, and most probably nonalcoholic fatty liver disease. In general, men are two to four times more often associated with HCC than women. It can be suggested that sex hormones including progesterone may play some roles in HCC. Rather, very limited information discusses its potential involvement in HCC. This paper thus collects some recent studies of the potential involvement of progesterone and related compounds in HCC from basic and clinical aspects. In addition, two synthetic progestins, megestrol acetate (MA and medroxyprogesterone acetate (MPA, will be discussed thoroughly. It is noted that progesterone can also serve as the precursor for androgens and estrogens produced by the gonadal and adrenal cortical tissues, while men have a higher incidence of HCC than women might be due to the stimulatory effects of androgen and the protective effects of estrogen. Eventually, this paper suggests a new insight on the associations of progesterone and related compounds with HCC development and treatment.

  9. Development of a competitive lateral flow immunoassay for progesterone: influence of coating conjugates and buffer components.

    Science.gov (United States)

    Posthuma-Trumpie, Geertruida A; Korf, Jakob; van Amerongen, Aart

    2008-11-01

    Several aspects of the development of competitive lateral flow immunoassays (LFIAs) are described. The quantitation of progesterone is taken as an example. The LFIA format consisted of a nitrocellulose membrane spotted with various progesterone conjugates as the test line. A mixture of primary antibody and secondary antibody adsorbed to colloidal carbon was used for signal generation. A digital scanner and dedicated software were used to quantitate the response. A reappraisal of the checkerboard titration, often used in the optimisation of immunoassays, is discussed. Surprisingly, the highest sensitivity of the LFIA format (IC(50) of 0.6 microg L(-1) progesterone in buffer) was achieved by using a high coating concentration of the analyte-protein conjugate and a high dilution of the antibody solution. Immediate addition of all reagents in LFIA was superior to premixing the components and allowing prereaction. Of several blocking agents tested bovine serum albumin was superior in performance, whereas the combination of ovalbumin and progesterone substantially influenced test results.

  10. Influence of the reuse of progesterone implants in a fixed-time ...

    African Journals Online (AJOL)

    This study aimed to evaluate the influence of reusing progesterone intravaginal implants using a fixed-time artificial insemination (FTAI) protocol on the conception rates of 593 primiparous and multiparous lactating cows during two different seasons. The cows were divided into two categories: multiparous and primiparous.

  11. Mammary gland lactose, plasma progesterone and lactogenesis in the marsupial Macropus eugenii.

    Science.gov (United States)

    Findlay, L; Ward, K L; Renfree, M B

    1983-06-01

    Mammary gland lactose concentrations in pregnant tammar wallabies remained low at 115 +/- 24 (S.E.M.) micrograms/g wet weight of tissue until immediately before parturition, then increased to 1274 +/- 262 micrograms/g after birth. Concentrations in non-pregnant cyclic animals were generally low (143 +/- 36 micrograms/g), but were raised in three animals around the time of oestrus. Removal of the corpus luteum on day 18 of pregnancy or the oestrous cycle caused an increase in lactose concentrations in both lutectomized and sham-operated animals. This occurred despite a significant lowering of peripheral plasma progesterone concentration in only the lutectomized group. Plasma cortisol concentrations were high in some of these animals, but showed no consistent relationships with the raised lactose concentrations. The increased peripartum lactose concentration normally coincides with a sharp fall in peripheral plasma progesterone concentration, but artificial maintenance of high progesterone levels had no effect on the increase of mammary gland lactose at parturition. Mammary gland lactose concentrations in tammar wallabies are therefore a useful indicator of biosynthetic activity and as an index of lactogenesis but the role, if any, of progesterone withdrawal in lactogenesis remains unclear.

  12. Artificial cryopreserved embryo transfer cycle success depends on blastocyst developmental rate and progesterone timing

    DEFF Research Database (Denmark)

    Ozgur, Kemal; Bulut, Hasan; Berkkanoglu, Murat

    2018-01-01

    This retrospective cohort analysis compared the developmental competence of cryopreserved day-4 and 5 blastocysts, and investigated the effect of progesterone administration duration on the success of artificial frozen embryo transfers. Between October 2015 and March 2016, 868 intracytoplasmic....... The retrospective analysis and lack of adjustment for all known confounding variables limit the study....

  13. Plasma prolactin, progesterone and oestradiol-17β concentrations around parturition in the pig

    NARCIS (Netherlands)

    Taverne, M.; Willemse, A.H.; Dieleman, S.J.; Bevers, M.

    Plasma concentrations of prolactin, progesterone and oestradiol-17β were measured by radioimmunoassay in samples taken from 2–15 days before until 1–4 days after spontaneous parturition in four sows and in one sow around prostaglandin F2α-induced parturition. Between Days −15 and −2 (Day 0 =

  14. The relationship between fat and progesterone, estradiol, and chorionic gonadotropin levels in Quebec cow's milk.

    Science.gov (United States)

    Gilman, A R; Buckett, W; Son, W Y; Lefebvre, J; Mahfoudh, A M; Dahan, M H

    2017-11-01

    The majority of milk in industrialized countries is obtained from pregnant cows, which contains increased levels of estrogen and progesterone compared to non-pregnant cows. The aim of this study was to quantify the amount of hormones present in milk with different fat content because previous studies on humans have shown potential effects of increased milk consumption on serum and urine hormone levels as well as on sperm parameters. However, it is unclear whether consumption of milk at the currently recommended levels would lead to systemic effects. Samples of cow's milk of varying fat concentrations (0, 1, 2, 3.25, 10, and 35%) were analyzed via competitive ELISA assays. Progesterone concentrations were significantly correlated to increasing fat content of milk (r = 0.8251, p = 0.04). Research on conditions in which additional progesterone may have an effect on human health should consider inclusion of limitation of milk intake and its effects. Further studies are needed to determine the concentration of progesterone in milk of different fat content in other regions and countries and to quantify the potential pathophysiologic role.

  15. Temporary undernutrition during early gestation, corpora lutea morphometrics, ovarian progesterone secretion and embryo survival in gilts

    NARCIS (Netherlands)

    Langendijk, P.; Bouwman, E.G.; Chen, T.; Koopmanschap, R.E.; Soede, N.M.

    2017-01-01

    The present study reports effects of severe undernutrition on luteal function and pregnancy in pigs. Gilts were inseminated and either fasted on Day 10 and 11 after conception (n = 11) or fully fed throughout (n = 10). Fasting did not affect LH or progesterone pulsatile secretion pattern on Day 11

  16. G-protein coupled progesterone receptors in the plasma membrane of fungus Rhizopus nigricans.

    Science.gov (United States)

    Bavec, A; Slajpah, M; Lenasi, H; Yorko, M; Breskvar, K

    2000-01-01

    We have demonstrated simultaneous existence of progesterone receptors and GTPase activity in the membranes prepared from the filamentous fungus Rhizopus nigricans. The results obtained with pertussis toxin treated fungal mycelium suggest that these receptors do not couple to Gi-Go-proteins and play a role in the induction of steroid hydroxylating enzyme system by steroid substrates in the fungus.

  17. Progesterone side-chain degradation beside hydroxylation with Rhizopus nigricans depends on the presence of nutrients.

    Science.gov (United States)

    Pokorná, J; Kasal, A

    1990-01-01

    In the absence of nutrients, Rhizopus nigricans transforms progesterone into a mixture of 11 alpha-hydroxy-4-androstene-3,17-dione and 11 alpha-hydroxy-1,4-adrostadiene-3,17-dione. The same mixture is obtained by the transformation of testosterone and its acetate.

  18. Plasma progesterone profile and ovarian activity of forced-moult layers

    African Journals Online (AJOL)

    Owner

    treatments in a completely randomized design, as follows: natural day length with feed and water ad libitum, natural day length with water but no feed, natural ... kept below 0oC in a freezer until required for assay of progesterone. Blood samples collected from birds of the same treatment group on each sampling day were.

  19. Testosterone and progesterone concentrations in blow samples are biologically relevant in belugas (Delphinapterus leucas).

    Science.gov (United States)

    Richard, Justin T; Robeck, Todd R; Osborn, Steven D; Naples, Lisa; McDermott, Alexa; LaForge, Robert; Romano, Tracy A; Sartini, Becky L

    2017-05-15

    Steroid hormone analysis in blow (respiratory vapor) may provide a minimally invasive way to assess the reproductive status of wild cetaceans. Biological validation of the method is needed to allow for the interpretation of hormone measurements in blow samples. Utilizing samples collected from trained belugas (Delphinapterus leucas, n=20), enzyme immunoassays for testosterone and progesterone were validated for use with beluga blow samples. Testosterone concentrations in 40 matched blood and blow samples collected from 4 male belugas demonstrated a positive correlation (R 2 =0.52, pblow samples from 11 females were also positively correlated (R 2 =0.60, pblow samples collected from adult males (119.3±14.2pg/ml) were higher (pblow demonstrated a seasonal pattern of secretion, with peak secretion occurring during the breeding season (February-April, 136.95±33.8pg/ml). Progesterone concentrations in blow varied by reproductive status; pregnant females (410.6±87.8pg/ml) and females in the luteal phase of the estrous cycle (339.5±51.0pg/ml) had higher (pblow progesterone concentrations than non-pregnant females without a corpus luteum (242.5±27.3pg/ml). Results indicate that blow sample analysis can be used to detect variation in reproductive states associated with large differences in circulating testosterone or progesterone in belugas. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Progesterone as a neuroprotective factor in traumatic and ischemic brain injury.

    Science.gov (United States)

    Sayeed, Iqbal; Stein, Donald G

    2009-01-01

    The search for a "magic bullet" drug targeting a single receptor for the treatment of stroke or traumatic brain injury (TBI) has failed thus far for a variety of reasons. The pathophysiology of ischemic brain injury and TBI involves a number of mechanisms leading to neuronal injury, including excitotoxicity, free radical damage, inflammation, necrosis, and apoptosis. Brain injury also triggers auto-protective mechanisms, including the up-regulation of anti-inflammatory cytokines and endogenous antioxidants. In these conditions an agent with pleiotropic consequences is more likely to provide effective neuroprotection and repair than one operating primarily on a single, or a small number of, injury mechanisms. There is growing evidence, including recently published clinical trials, that progesterone and perhaps its metabolite allopregnanolone exert neuroprotective effects on the injured central nervous system (CNS). Laboratories around the world have shown that progesterone and allopregnanolone act through numerous metabolic and physiological pathways that can affect the injury response in many different tissues and organ systems. Furthermore, progesterone is a natural hormone, synthesized in both males and females, that can act as a pro-drug for other metabolites with their own distinct mode of action in CNS repair. These properties make progesterone a unique and compelling natural agent to consider for testing in clinical trial for CNS injuries including TBI and stroke.

  1. Prognostic Value of Estrogen Receptor alpha and Progesterone Receptor Conversion in Distant Breast Cancer Metastases

    NARCIS (Netherlands)

    Hoefnagel, Laurien D. C.; Moelans, Cathy B.; Meijer, S. L.; van Slooten, Henk-Jan; Wesseling, Pieter; Wesseling, Jelle; Westenend, Pieter J.; Bart, Joost; Seldenrijk, Cornelis A.; Nagtegaal, Iris D.; Oudejans, Joost; van der Valk, Paul; van Gils, Carla H.; van der Wall, Elsken; van Diest, Paul J.

    2012-01-01

    BACKGROUND: Changes in the receptor profile of primary breast cancers to their metastases (receptor conversion) have been described for the estrogen receptor alpha (ER alpha) and progesterone receptor (PR). The purpose of this study was to evaluate the impact of receptor conversion for ER alpha and

  2. Relationship between progesterone concentrations in milk and blood and time of ovulation in dairy cattle

    NARCIS (Netherlands)

    Roelofs, J.B.; Eerdenburg, van F.J.C.M.; Hazeleger, W.; Soede, N.M.; Kemp, B.

    2006-01-01

    The objective of this study was to investigate whether monitoring progesterone concentrations in milk and blood plasma can be used to predict time of ovulation in dairy cattle. Whole milk was sampled twice daily and blood samples were collected once a day before the morning milking. Ovulation was

  3. Arthrospira (Spirulina) platensis supplementation affects folliculogenesis, progesterone and ghrelin levels in fattening pre-pubertal gilts

    NARCIS (Netherlands)

    Abadjieva, Desislava; Nedeva, Radka; Marchev, Yordan; Jordanova, Gergana; Chervenkov, Mihail; Dineva, Julieta; Shimkus, Almantas; Shimkiene, Aldona; Teerds, Katja; Kistanova, Elena

    2017-01-01

    The aim of the present investigation was to study the effect of Arthrospira (Spirulina) platensis supplemented diet on follicular development and related endocrine parameters, such as estradiol and progesterone levels as well as ghrelin levels in pre-pubertal gilts. Twenty-one 60-day-old Danube

  4. Serum progesterone as an indicator of cyclic activity in post-partum ...

    African Journals Online (AJOL)

    The aim of this trial was to assess post-partum ovarian activity of the does of two South African goat breeds from their serum progesterone concentrations. Between seven and 100 days post-partum, does from the Boer goat breed and an indigenous rural goat type were allocated to two nutritional treatments within breed.

  5. COUP-TFII mediates progesterone regulation of uterine implantation by controlling ER activity.

    Directory of Open Access Journals (Sweden)

    Isao Kurihara

    2007-06-01

    Full Text Available Progesterone and estrogen are critical regulators of uterine receptivity. To facilitate uterine remodeling for embryo attachment, estrogen activity in the uterine epithelia is attenuated by progesterone; however, the molecular mechanism by which this occurs is poorly defined. COUP-TFII (chicken ovalbumin upstream promoter transcription factor II; also known as NR2F2, a member of the nuclear receptor superfamily, is highly expressed in the uterine stroma and its expression is regulated by the progesterone-Indian hedgehog-Patched signaling axis that emanates from the epithelium. To further assess COUP-TFII uterine function, a conditional COUP-TFII knockout mouse was generated. This mutant mouse is infertile due to implantation failure, in which both embryo attachment and uterine decidualization are impaired. Using this animal model, we have identified a novel genetic pathway in which BMP2 lies downstream of COUP-TFII. Epithelial progesterone-induced Indian hedgehog regulates stromal COUP-TFII, which in turn controls BMP2 to allow decidualization to manifest in vivo. Interestingly, enhanced epithelial estrogen activity, which impedes maturation of the receptive uterus, was clearly observed in the absence of stromal-derived COUP-TFII. This finding is consistent with the notion that progesterone exerts its control of implantation through uterine epithelial-stromal cross-talk and reveals that stromal-derived COUP-TFII is an essential mediator of this complex cross-communication pathway. This finding also provides a new signaling paradigm for steroid hormone regulation in female reproductive biology, with attendant implications for furthering our understanding of the molecular mechanisms that underlie dysregulation of hormonal signaling in such human reproductive disorders as endometriosis and endometrial cancer.

  6. Biomechanical properties of osteoporotic rat femurs after different hormonal treatments: genistein, estradiol, and estradiol/progesterone

    Directory of Open Access Journals (Sweden)

    Azboy İbrahim

    2016-01-01

    Full Text Available Introduction: The purpose of the study is to compare the effects of genistein, estradiol, estradiol/progesterone combination on the bone mineral density and biomechanical properties of ovariectomized rats’ bone. Methods: 50 female adult Sprague-Dawley rats were divided into five groups. Bilaterally ovaeriectomy were performed in all groups except the sham-operated group. Groups were a sham-operated group and a control group (water was given, estradiol treated group (17-β estradiol 0.015 mg/kg per day, genistein treated group (genistein 10 mg/kg per day, and an estradiol/progesterone combination group (17-β estradiol 0.015 mg/kg plus drosperinone 0.028 mg/kg per day. The water or hormones were implemented in relevant groups for eight weeks by orogasthric catheter. The bone mineral density and biomechanical properties of the femur were analyzed. Results: Genistein, estradiol, and estradiol/progesterone groups increased bone mineral density significantly compared to the control group. In diaphysis and metaphysis bending test, all groups had higher peak load values than the control group. There were statistically significant differences between the estrogen/progesterone group and control group in diaphysis bending with regard to peak load. There were statistically significant differences between the estradiol and control groups in metaphysis bending with regard to peak load. In axial rotation test, all groups had higher peak torque values than the control groups. Conclusions: Genistein, estradiol and estrogen/progesterone combination improved the biomechanical properties of the ovariectomized rat bone. Genistein which has less side effects may be considered as an alternative in the treatment of postmenopausal osteoporosis.

  7. Estradiol implants in the arcuate nucleus induce lactogenesis in virgin rats. Role of progesterone.

    Science.gov (United States)

    Carón, R W; Deis, R P

    1998-01-01

    The aim of this study was to determine the effect of the centrally administered estradiol, and the effects of the consequent hypersecretion of prolactin (PRL) and progesterone, on lactogenesis as evaluated by mammary accumulation of casein and lactose. Bilateral cannulae containing 17beta-estradiol or cholesterol were implanted in the arcuate nucleus of virgin rats on the day of estrus (Day 0). In the first experiment different groups of rats were killed on Days 6, 9, 15, 17, or 19. Trunk blood was collected and abdominal mammary glands were taken. In the second experiment, estradiol-implanted rats received the progesterone antagonist mifepristone or vehicle at 14.00 h on Day 8 or 16 post-implant, and were killed 28 or 48 h later. Serum PRL and progesterone and mammary casein were measured by RIA and lactose was determined by an enzymatic assay. Estradiol-implanted rats showed a significant increase in both milk components at all time points after implant compared to controls. On Day 9 after estradiol implant, mifepristone had no effect on mammary content of casein or lactose. By contrast, on Day 16, mifepristone markedly increased both casein and lactose contents without modifying serum PRL and progesterone concentrations. In conclusion, 17beta-estradiol implants in the arcuate nucleus of virgin rats results in hyperprolactinaemia and stimulates mammary accumulation of casein and lactose in the absence of feto-placental units. Despite the prolonged luteal activation, the sustained high levels of circulating progesterone become inhibitory to lactogenesis after a relatively long period after implant.

  8. Respiratory responses to progesterone and allopregnanolone following chronic caffeine treatment in newborn female rats.

    Science.gov (United States)

    Uppari, Naga Praveena; Joseph, Vincent; Bairam, Aida

    2017-06-01

    We recently showed that in 12-day-old male rats exposed to caffeine for 10 consecutive days, progesterone inhibits the respiratory response to hypoxia and increases apnea frequency (Uppari et al., 2016). This was partly due to a higher inhibitory response of GABAa receptor to allopregnanolone, the neuroactive metabolite of progesterone. In the present study, we addressed whether similar effects occur in females. We used newborn female rats daily gavaged with water (control) or caffeine (15mg/kg) between the postnatal (P) days 3-12. At P12, we recorded ventilation, metabolic rate, and apnea frequency and duration in normoxia and in response to moderate hypoxia, following an intraperitonial injection of progesterone (4mg/kg) or allopregnanolone (10mg/kg). In control rats, progesterone had no effect on breathing in normoxia and in hypoxia, and in rats treated with caffeine it decreased the initial increase in respiratory frequency in hypoxia. In both groups, allopregnalone decreased breathing frequency in normoxia and in hypoxia and increased the frequency of apnea in normoxia in control rats and in rats treated with caffeine. Injection of bicuculline (a specific GABAa receptor antagonist) prevented the inhibitory effects of allopregnanolone on breathing in both groups. These data indicate that chronic caffeine treatment unmasked an inhibitory effect of progesterone on the hypoxic response but this was weaker than in males, and contrasting to what was observed in male rats (Uppari et al., 2016), GABAa receptors are not significantly affected by chronic caffeine treatment in newborn female rats. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Membrane progesterone receptor beta (mPR?/Paqr8) promotes progesterone-dependent neurite outgrowth in PC12 neuronal cells via non-G protein-coupled receptor (GPCR) signaling

    OpenAIRE

    Kasubuchi, Mayu; Watanabe, Keita; Hirano, Kanako; Inoue, Daisuke; Li, Xuan; Terasawa, Kazuya; Konishi, Morichika; Itoh, Nobuyuki; Kimura, Ikuo

    2017-01-01

    Recently, sex steroid membrane receptors garnered world-wide attention because they may be related to sex hormone-mediated unknown rapid non-genomic action that cannot be currently explained by their genomic action via nuclear receptors. Progesterone affects cell proliferation and survival via non-genomic effects. In this process, membrane progesterone receptors (mPRα, mPRβ, mPRγ, mPRδ, and mPRε) were identified as putative G protein-coupled receptors (GPCRs) for progesterone. However, the st...

  10. Effect of Progesterone Therapy on TNF-α and iNOS Gene Expression in Spinal Cord Injury Model

    Directory of Open Access Journals (Sweden)

    Akram Farahabadi

    2016-06-01

    Full Text Available Spinal cord injury (SCI as a destructive crash result in neurons degeneration. The SCI lead to the onset of biochemical and molecular cascades such as inflammation that in turn has a key role in neurodegeneration development. The previous studies demonstrated the role of TNF-α and iNOS genes in intensifying the process after SCI. As a consequence, these genes overexpression intensify the inflammation and neuron degeneration process. In the present study, 32 male Wistar rats were chased and divided into four groups of eight. The SCI were induced in three groups and another group used as a sham. The progesterone hormone used as a therapeutic agent in rats with SCI. The results showed that injection of 10 μg/kg/12h progesterone hormone reduced the TNF-α and iNOS gene expression significantly and confirmed the role of progesterone in the reduction of inflammation. Also, the numbers of intact neurons in progesterone group were higher than other groups that demonstrated the protective effects of progesterone on neuron death. The BBB test was performed and demonstrated that progesterone is an effective factor to the improvement of locomotor response. These results of the study confirmed the anti-inflammatory activity of progesterone hormone and suggested that it can be used as a therapeutic factor for SCI.

  11. Progesterone-induced stimulation of mammary tumorigenesis is due to the progesterone metabolite, 5α-dihydroprogesterone (5αP) and can be suppressed by the 5α-reductase inhibitor, finasteride.

    Science.gov (United States)

    Wiebe, John P; Rivas, Martin A; Mercogliano, Maria F; Elizalde, Patricia V; Schillaci, Roxana

    2015-05-01

    Progesterone has long been linked to breast cancer but its actual role as a cancer promoter has remained in dispute. Previous in vitro studies have shown that progesterone is converted to 5α-dihydroprogesterone (5αP) in breast tissue and human breast cell lines by the action of 5α-reductase, and that 5αP acts as a cancer-promoter hormone. Also studies with human breast cell lines in which the conversion of progesterone to 5αP is blocked by a 5α-reductase inhibitor, have shown that the in vitro stimulation in cell proliferation with progesterone treatments are not due to progesterone itself but to the metabolite 5αP. No similar in vivo study has been previously reported. The objective of the current studies was to determine in an in vivo mouse model if the presumptive progesterone-induced mammary tumorigenesis is due to the progesterone metabolite, 5αP. BALB/c mice were challenged with C4HD murine mammary cells, which have been shown to form tumors when treated with progesterone or the progestin, medroxyprogesterone acetate. Cells and mice were treated with various doses and combinations of progesterone, 5αP and/or the 5α-reductase inhibitor, finasteride, and the effects on cell proliferation and induction and growth of tumors were monitored. Hormone levels in serum and tumors were measured by specific RIA and ELISA tests. Proliferation of C4HD cells and induction and growth of tumors was stimulated by treatment with either progesterone or 5αP. The progesterone-induced stimulation was blocked by finasteride and reinstated by concomitant treatment with 5αP. The 5αP-induced tumors expressed high levels of ER, PR and ErbB-2. Hormone measurements showed significantly higher levels of 5αP in serum from mice with tumors than from mice without tumors, regardless of treatments, and 5αP levels were significantly higher (about 4-fold) in tumors than in respective sera, while progesterone levels did not differ between the compartments. The results indicate that

  12. The effects of intrahippocampus injection of progesterone on passive avoidance learning and memory in adult male rats

    Directory of Open Access Journals (Sweden)

    Tahmoores Shahrivar

    2014-10-01

    Full Text Available Background: Progesterone as a reproductive hormone is studied in the brain structure. New studies are mainly about systemic injection and have shown that the progesterone has different effects on memory. But it is not clear if hippocampus is mediator of progesterone in reinforcement of memory and learning. So, the effects of intra-hippocampal injection of progesterone on passive avoidance memory and learning was studied in male Wistar rats. Material and Methods: Animals were divided in eightgroups as a control, saline, almond oil (as a vehicle and progesterone groups (0.5, 1, 1.5, 2, 3µg/Kg. body weight. All groups except the control were cannulated in left CA1 area by stereotaxic device. One week after recovery, all groups were trained by shuttle box and immediately after training different doses of progesterone in the volume of 0.5μL were injected through the cannula in CA1 of hippocampus and control groups received saline and almond oil at the same volume and condition respectively. After 48 hours passive avoidance memory and learning was evaluated. Results: Statistical analysis showed that 0.5, 1.5, 2 µg/µl progesterone groups had significantly improved passive avoidance learning and memory compared with saline group (p <0.001, but 1 and 3 µg/µl progesterone groups did not show significant effect on passive avoidance learning and memory compared with saline group. Also almond oil increased passive avoidance learning and memory compared with saline group (p <0.001. Conclusion: It seems that effects of progesterone as a neurosteroid on memory and learning depend on its dose. Also almond oil contains vitamin E, omega 3 and oleic acid that has beneficial effects on learning and memory.

  13. Mathematical characterization of the milk progesterone profile as a leg up to individualized monitoring of reproduction status in dairy cows.

    Science.gov (United States)

    Adriaens, Ines; Huybrechts, Tjebbe; Geerinckx, Katleen; Daems, Devin; Lammertyn, Jeroen; De Ketelaere, Bart; Saeys, Wouter; Aernouts, Ben

    2017-11-01

    Reproductive performance is an important factor affecting the profitability of dairy farms. Optimal fertility results are often confined by the time-consuming nature of classical heat detection, the fact that high-producing dairy cows show estrous symptoms shorter and less clearly, and the occurrence of ovarian problems. Today's commercially available solutions for automatic estrus detection include monitoring of activity, temperature and progesterone. The latter has the advantage that, besides estrus, it also allows to detect pregnancy and ovarian problems. Due to the large variation in progesterone profiles, even between cycles within the same cow, the use of general thresholds is suboptimal. To this end, an intelligent and individual interpretation of the progesterone measurements is required. Therefore, an alternative solution is proposed, which takes individual and complete cycle progesterone profiles into account for reproduction monitoring. In this way, profile characteristics can be translated into specific attentions for the farmers, based on individual rather than general guidelines. To enable the use of the profile and cycle characteristics, an appropriate model to describe the milk progesterone profile was developed. The proposed model describes the basal adrenal progesterone production and the growing and regressing cyclic corpus luteum. To identify the most appropriate way to describe the increasing and decreasing part of each cycle, three mathematical candidate functions were evaluated on the increasing and decreasing parts of the progesterone cycle separately: the Hill function, the logistic growth curve and the Gompertz growth curve. These functions differ in the way they describe the sigmoidal shape of each profile. The increasing and decreasing parts of the P4 cycles were described best by the model based on respectively the Hill and Gompertz function. Combining these two functions, a full mathematical model to characterize the progesterone cycle

  14. Progesterone amplifies oxidative stress signal and promotes NO production via H2O2 in mouse kidney arterial endothelial cells.

    Science.gov (United States)

    Yuan, Xiao-Hua; Fan, Yang-Yang; Yang, Chun-Rong; Gao, Xiao-Rui; Zhang, Li-Li; Hu, Ying; Wang, Ya-Qin; Jun, Hu

    2016-01-01

    The role of progesterone on the cardiovascular system is controversial. Our present research is to specify the effect of progesterone on arterial endothelial cells in response to oxidative stress. Our result showed that H2O2 (150 μM and 300 μM) induced cellular antioxidant response. Glutathione (GSH) production and the activity of Glutathione peroxidase (GPx) were increased in H2O2-treated group. The expression of glutamate cysteine ligase catalytic subunit (GCLC) and modifier subunit (GCLM) was induced in response to H2O2. However, progesterone absolutely abolished the antioxidant response through increasing ROS level, inhibiting the activity of Glutathione peroxidase (GPx), decreasing GSH level and reducing expression of GClC and GCLM. In our study, H2O2 induced nitrogen monoxide (NO) production and endothelial nitric oxide synthase (eNOS) expression, and progesterone promoted H2O2-induced NO production. Progesterone increased H2O2-induced expression of hypoxia inducible factor-α (HIFα) which in turn regulated eNOS expression and NO synthesis. Further study demonstrated that progesterone increased H2O2 concentration of culture medium which may contribute to NO synthesis. Exogenous GSH decreased the content of H2O2 of culture medium pretreated by progesterone combined with H2O2 or progesterone alone. GSH also inhibited expression of HIFα and eNOS, and abolished NO synthesis. Collectively, our study demonstrated for the first time that progesterone inhibited cellular antioxidant effect and increased oxidative stress, promoted NO production of arterial endothelial cells, which may be due to the increasing H2O2 concentration and amplified oxidative stress signal. Copyright © 2015. Published by Elsevier Ltd.

  15. A State Space Model Exhibiting a Cyclic Structure with an Application to Progesterone Concentration in Cow Milk

    DEFF Research Database (Denmark)

    Hansen, Jørgen Vinsløv; Jensen, Jens Ledet; Højsgaard, Søren

    Progesterone is a hormone linked to the reproductive status of dairy cows. Hence, with the increasing availability of on-line records of the concentration of progesterone in cow milk, there is a need for new tools to analyse such data. The aim is to find techniques for better determination...... of the time when cows are in oestrus to increase the rate of succesful inseminations. In this paper we propose a state space model for data with a continuous and cyclic trend in the mean. Furthermore a matching Kalman filter is developed. The model is tested on progesterone data from 112 cow...

  16. Effect of progesterone pretreatment on cadmium toxicity in male Fischer (F344/NCr) and Wistar (WF/NCr) rats.

    OpenAIRE

    Shiraishi, N.; Barter, R. A.; Uno, H.; Waalkes, M P

    1994-01-01

    A previous report indicated that progesterone pretreatment can markedly reduce cadmium (Cd) toxicity in male NAW mice. Therefore we examined the effects of progesterone pretreatment on Cd toxicity in male Fischer (F344) and Wistar (WF) rats. A single subcutaneous injection of 10 or 30 mumole (CdCl2)/kg proved nonlethal over 24 hr but caused the typical spectrum of testicular lesions in these rats. Moreover, when F344 rats were pretreated with progesterone (100 mg/kg, sc, at -48, -24, and 0 hr...

  17. In situ detection of progesterone binding sites in the plasma membrane of the filamentous fungus Rhizopus nigricans: In situ detekcija vezavnih mest za progesteron v plazemski membrani filamentozne glive Rhizopus nigricans:

    OpenAIRE

    Breskvar, Katja; Jeraj, Nataša; LENASI, HELENA; Romih, Rok

    2003-01-01

    Steroid hydroxylating enzymes in the fungus Rhizopus nigricans are induced by progesterone and by some other steroids. It is known that in higher organisms steroids exert their nongenomic action via steroid binding proteins located inthe plasma membrane of the cells, thus our aim was to detect progesterone binding sites in R. nigricans plasma membrane. In this report membrane receptors were identified by two independent methods, analysis of progesteronebinding to plasma membrane fraction by c...

  18. Intrahepatic cholestasis of pregnancy levels of sulfated progesterone metabolites inhibit farnesoid X receptor resulting in a cholestatic phenotype

    National Research Council Canada - National Science Library

    Abu‐Hayyeh, Shadi; Papacleovoulou, Georgia; Lövgren‐Sandblom, Anita; Tahir, Mehreen; Oduwole, Olayiwola; Jamaludin, Nurul Akmal; Ravat, Sabiha; Nikolova, Vanya; Chambers, Jenny; Selden, Clare; Rees, Myrddin; Marschall, Hanns‐Ulrich; Parker, Malcolm G; Williamson, Catherine

    2013-01-01

    ...)‐mediated bile acid homeostasis pathways. Here we report that the 3β‐sulfated progesterone metabolite epiallopregnanolone sulfate is supraphysiologically raised in the serum of ICP patients...

  19. Cloning and initial characterization of nuclear and four membrane progesterone receptors in the fathead minnow(Pimephales promelas)

    Science.gov (United States)

    Both native progestagens and synthetic progestins have important effects on reproduction that are mediated through progesterone receptors (PRs). Progestagens regulate gamete maturation in vertebrates, are critical regulators of placental mammal pregnancy, and act as reproductive ...

  20. Factors affecting the induction of 11 alpha-hydroxylase of progesterone in the filamentous fungus Rhizopus nigricans.

    Science.gov (United States)

    Hudnik-Plevnik, T; Cresnar, B

    1990-05-01

    The 11 alpha-hydroxylase of progesterone was induced in the filamentous fungus Rhizopus nigricans ATCC 6227b with different steroids as inducers and the induction process was optimized in regard to the age of the mycelium, to the concentration of the inducer and to the time of induction. Deoxycorticosterone and testosterone, steroids with higher polarity of the side-chain than progesterone, although poorer substrates for in vivo hydroxylation than progesterone, induced more enzyme compared to progesterone. Other alterations in the steroidal ring system examined diminished the induction capability of the inducing steroid to different extent. The highest 11 alpha-hydroxylating activity, if expressed on the basis of mycelial wet weight, was achieved with 18 h old mycelium which was induced for 2 h with 0.30 mM deoxycorticosterone.

  1. Biochemical and immunohistochemical estrogen and progesterone receptors in adenomatous hyperplasia and endometrial carcinoma: correlations with stage and other clinicopathologic features

    DEFF Research Database (Denmark)

    Nyholm, H C; Nielsen, A L; Lyndrup, J

    1992-01-01

    and immunohistochemical analysis were used. The immunohistochemical analysis receptor content was estimated semiquantitatively by a total and a cancer immunohistochemical histologic score. Multiple regression analysis was used in testing independence of established correlations. RESULTS: Estrogen and progesterone...

  2. Progesterone Supplement and Luteal Phase Deficiency in Unifollicular Intrauterine Insemination Cycles

    Directory of Open Access Journals (Sweden)

    Kadir Bakay

    2014-03-01

    Full Text Available Aim: Intrauterine insemination is a widely used technique with advantages of being a simple and less invasive method with a lower cost when compared to other assisted reproductive techniques. In the present prospective randomized controlled study we aim to prove that progesterone supplementation is a beneficial factor in pregnancies achieved with intra uterine insemination and also we want to emphasise that luteal phase deficiency does not always occur in multifollicular cycles but can be seen in unifollicular cycles as well. Material and Method: Patients diagnosed with unexplained infertility between December 2011 and December 2012 were admitted to the study group. 278 IUI cycles with COH using recombinant FSH induction were recorded. Results: The effect of progesterone supplement on achieving pregnancy was statistically significant (p

  3. Electron emission and product analysis of estrone: progesterone interactions studied by experiments in vitro.

    Science.gov (United States)

    Gerschpacher, Marion; Getoff, Nikola; Hartmann, Johannes; Schittl, Heike; Danielova, Iren; Ying, Shaobin; Huber, Johannes C; Quint, Ruth M

    2011-07-01

    Recent studies showed that hormones like progesterone, testosterone, etc. can eject [Formula: see text] (solvated electrons). By means of electron transfer processes via the brain, the hormones communicate with other biological systems in the organism. The present study proves that also estrone is able to emit electrons. Their yield strongly depends on the concentration of the hormone, temperature and on the absorbed energy. The metabolites resulting from this process are likewise able to generate electrons, however with much smaller yields. The formation of the estrone metabolites is studied by HPLC-analyses. In vitro experiments with MCF-7 cells demonstrate the distinct effect of progesterone on the carcinogenity of estrone metabolites. Probable reaction mechanisms for explanation of the observed effects are postulated.

  4. Meta-analysis of progesterone supplementation during timed artificial insemination programs in dairy cows.

    Science.gov (United States)

    Bisinotto, R S; Lean, I J; Thatcher, W W; Santos, J E P

    2015-04-01

    A systematic review of the literature was performed with the objective to evaluate the effects of progesterone supplementation using a single intravaginal insert during timed artificial insemination (AI) programs on fertility in lactating dairy cows. A total of 25 randomized controlled studies including 8,285 supplemented cows and 8,398 untreated controls were included in the meta-analysis. Information regarding the presence of corpus luteum (CL) at the initiation of the synchronization protocol was available for 6,883 supplemented cows and 6,879 untreated controls in 21 experiments. Studies were classified based on service number (first AI vs. resynchronized AI), use of presynchronization (yes vs. no), and insemination of cows in estrus during the synchronization protocol (inseminated in estrus and timed AI vs. timed AI only). Reproductive outcomes of interest were pregnancy per AI (P/AI) measured on d 32 (27 to 42) and 60 (41 to 71) after AI, and pregnancy loss between d 32 and 60 of gestation. Random effects meta-analyses were conducted and treatment effect was summarized into a pooled risk ratio with the Knapp-Hartung modification (RRK+H). The effect of moderator variables was assessed using meta-regression analyses. Progesterone supplementation increased the risk of pregnancy on d 32 [RRK+H = 1.08; 95% confidence interval (CI) = 1.02-1.14] and 60 after AI (RRK+H = 1.10; 95% CI = 1.03-1.17). The benefit of progesterone supplementation was observed mainly in cows lacking a CL at the initiation of the timed AI program (d 60: RRK+H = 1.18; 95% CI = 1.07-1.30) rather than those with CL (d 60: RRK+H = 1.06; 95% CI = 0.99-1.12). Progesterone supplementation benefited P/AI in studies in which all cows were inseminated at timed AI (d 60: RRK+H = 1.20; 95% CI = 1.10-1.29), but not in studies in which cows could be inseminated in estrus during the timed AI program (d 60: RRK+H = 1.04; 95% CI = 0.92-1.16). Progesterone supplementation tended to reduce the risk of

  5. Plasma oestrogen, progesterone and other reproductive responses of gilts to photoperiods.

    Science.gov (United States)

    Hacker, R R; King, G J; Ntunde, B N; Narendran, R

    1979-11-01

    Yorkshire gilts in 18 cool-white fluorescent light with 6 h dark daily and those in 9.0-10.8 h natural light exhibited puberty earlier (165 and 175 days: P less than 0.05) and had more corpora lutea (13.5 and 12.6: P less than 0.05) than those reared in complete darkness (200 days and 11.3 respectively). Weekly samples of plasma showed significant fluctuations of progesterone which confirmed the different times of the first over oestrus (puberty). In all 3 groups total oestrogen concentrations showed a peak at about 135 days. The correlation between oestrogen and progesterone values changed from a positive to a negative value at about 135 days of age. It is suggested that the oestrogen peak marks a time of change in sensitivity of the reproductive system to hormonal feedback.

  6. Estrogen- and progesterone-mediated structural neuroplasticity in women: evidence from neuroimaging.

    Science.gov (United States)

    Catenaccio, Eva; Mu, Weiya; Lipton, Michael L

    2016-11-01

    There is substantial evidence that the ovarian sex hormones, estrogen and progesterone, which vary considerably over the course of the human female lifetime, contribute to changes in brain structure and function. This structured, quantitative literature reviews aims to summarize neuroimaging literature addressing physiological variation in brain macro- and microstructure across an array of hormonal transitions including the menstrual cycle, use of hormonal contraceptives, pregnancy, and menopause. Twenty-five studies reporting structural neuroimaging of women, addressing variation across hormonal states, were identified from a structured search of PUBMED and were systematically reviewed. Although the studies are heterogenous with regard to methodology, overall the results point to overlapping areas of hormone related effects on brain structure particularly affecting the structures of the limbic system. These findings are in keeping with functional data that point to a role for estrogen and progesterone in mediating emotional processing.

  7. A germline TaqI restriction fragment length polymorphism in the progesterone receptor gene in ovarian carcinoma.

    OpenAIRE

    McKenna, N. J.; Kieback, D. G.; Carney, D N; Fanning, M.; McLinden, J.; Headon, D R

    1995-01-01

    Clinical outcome in ovarian carcinoma is predicted by progesterone receptor status, indicating an endocrine aspect to this disease. Peripheral leucocyte genomic DNAs were obtained from 41 patients with primary ovarian carcinoma and 83 controls from Ireland, as well as from 26 primary ovarian carcinoma patients and 101 controls in Germany. Southern analysis using a human progesterone receptor (hPR) cDNA probe identified a germline TaqI restriction fragment length polymorphism (RFLP) defined by...

  8. Correlation analysis of the progesterone-induced sperm acrosome reaction rate and the fertilisation rate in vitro.

    Science.gov (United States)

    Jiang, T; Qin, Y; Ye, T; Wang, Y; Pan, J; Zhu, Y; Duan, L; Li, K; Teng, X

    2015-10-01

    In this study, we aimed to investigate whether progesterone-induced acrosome reaction (AR) rate could be an indicator for fertilisation rate in vitro. Twenty-six couples with unexplained infertility and undergoing in vitro fertilisation (IVF) treatment were involved. On the oocytes retrieval day after routine IVF, residual sperm samples were collected to receive progesterone induction (progesterone group) or not (control group). AR rate was calculated and fertilisation rate was recorded. The correlation between progesterone-induced AR and fertilisation rate and between sperm normal morphology and 3PN (tripronuclear) were analysed using the Spearman correlation analysis. The AR rate of progesterone group was statistically higher than that of the control group (15.6 ± 5.88% versus 9.66 ± 5.771%, P rate (r = -0.053, P > 0.01) or rate of high-quality embryo development (r = -0.055, P > 0.01). Normal sperm morphology also showed no significant correlation with the amount of 3PN zygotes (r = 0.029, P > 0.01), rate of 3PN zygotes production (r = 0.20, P > 0.01), rate of 3PN embryo development (r = -0.406, P > 0.01), fertilisation rate (r = -0.148, P > 0.01) or progesterone-induced AR rate (r = 0.214, P > 0.01). Progesterone can induce AR in vitro significantly; however, the progesterone-induced AR may not be used to indicate fertilisation rate. © 2014 Blackwell Verlag GmbH.

  9. Increasing progesterone levels are associated with smoking abstinence among free-cycling women smokers who receive brief pharmacotherapy.

    Science.gov (United States)

    Saladin, Michael E; McClure, Erin A; Baker, Nathaniel L; Carpenter, Matthew J; Ramakrishnan, Viswanathan; Hartwell, Karen J; Gray, Kevin M

    2015-04-01

    Preclinical and human laboratory research suggests that (a) progesterone may decrease drug reward, craving, and smoking behavior, and (b) estradiol may enhance drug reward and smoking behavior. A modest majority of treatment research examining the relationship between menstrual cycle phase and outcomes suggests that the luteal menstrual phase, with its uniquely higher progesterone levels, is associated with better cessation outcomes. However, no studies to date have examined the effects of naturally occurring variation in progesterone and estradiol levels on medication-assisted smoking cessation. The present study sought to fill this notable gap in the treatment literature. Weekly plasma progesterone and estradiol levels were obtained from nicotine-dependent female smokers enrolled in a 4-week cessation trial. Participants (N = 108) were randomized to receive a 4-week course of either varenicline (VAR) tablets and placebo patches or placebo tablets and nicotine patches. Plasma samples were obtained 1 week before their cessation attempt and weekly during medication administration. Abstinence was assessed weekly. Weekly hormone data replicated commonly observed menstrual cycle patterns of progesterone and estradiol levels. Importantly, increases in progesterone level were associated with a 23% increase in the odds for being abstinent within each week of treatment. This effect was driven primarily by nicotine patch-treated versus VAR-treated females. This study was the first to identify an association between progesterone level (increasing) and abstinence outcomes in free-cycling women smokers who participated in a medication-based treatment. Furthermore, the potential benefits of progesterone may vary across different pharmacotherapies. Implications of these findings for smoking cessation intervention are discussed. © The Author 2015. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For

  10. Development of poly(lactic acid) nanostructured membranes for the controlled delivery of progesterone to livestock animals

    Energy Technology Data Exchange (ETDEWEB)

    Oliveira, Juliano Elvis [Laboratorio Nacional de Nanotecnologia para o Agronegocio (LNNA), Embrapa Instrumentacao (CNPDIA), Rua XV de Novembro, 1452, Centro, 13.560, 970 Sao Carlos, SP (Brazil); Medeiros, Eliton Souto [Universidade Federal da Paraiba (UFPB), Departamento de Engenharia de Materiais (DEMAT), Cidade Universitaria, 58.051-900, Joao Pessoa, PB (Brazil); Cardozo, Lucio; Voll, Fernando [Departamento de Engenharia Quimica, Universidade Estadual de Maringa (UEM), 87.020, 900 Maringa, PR (Brazil); Madureira, Ed Hoffmann [Departamento de Reproducao Animal, Faculdade de Medicina Veterinaria e Zootecnia (FMVZ), Universidade de Sao Paulo (USP), Pirassununga-SP (Brazil); Mattoso, Luiz Henrique Capparelli, E-mail: mattoso@cnpdia.embrapa.br [Laboratorio Nacional de Nanotecnologia para o Agronegocio (LNNA), Embrapa Instrumentacao (CNPDIA), Rua XV de Novembro, 1452, Centro, 13.560, 970 Sao Carlos, SP (Brazil); Assis, Odilio Benedito Garrido [Laboratorio Nacional de Nanotecnologia para o Agronegocio (LNNA), Embrapa Instrumentacao (CNPDIA), Rua XV de Novembro, 1452, Centro, 13.560, 970 Sao Carlos, SP (Brazil)

    2013-03-01

    Solution blow spinning (SBS) is a novel technology feasible to produce nanostructured polymeric membranes loaded with active agents. In the present study, nanofibrous mats of poly(lactic acid) (PLA) loaded with progesterone (P4) were produced by SBS at different P4 concentrations. The spun membranes were characterized by scanning electron microscopy (SEM), differential scanning calorimetry (DSC) and Fourier-transform infrared spectroscopy (FTIR). The in vitro releasing of P4 was evaluated using high-performance liquid chromatography (HPLC). Interactions between progesterone and PLA were confirmed by rheological measurements of the PLA/P4 solutions and in the spun mats by microscopy (SEM), thermal (DSC) and spectral (FTIR) analyses. SEM micrographs provided evidences of a smooth and homogeneous structure for nanostructured membranes without progesterone crystals on fiber surface. FTIR spectroscopy indicated miscibility and interaction between the ester of PLA and the ketone groups of the P4 in the nanofibers. X-ray analysis indicated that the size of PLA crystallites increased with progesterone content. Finally, by in vitro release experiments it was possible to observe that the progesterone releasing follows nearly first-order kinetics, probably due to the diffusion of hormone into PLA nanofibers. - Highlights: Black-Right-Pointing-Pointer Nanofibers of PLA loading with progesterone were prepared via solution blow spinning. Black-Right-Pointing-Pointer Their morphology, FTIR, and XRD and DSC characterization were analyzed. Black-Right-Pointing-Pointer Fibers of PLA/progesterone with diameters from 280 to 440 nm were obtained. Black-Right-Pointing-Pointer The effect of progesterone content in fiber properties was studied.

  11. Proliferative effects of combination estrogen and progesterone replacement therapy on the normal postmenopausal mammary gland in a murine model.

    Science.gov (United States)

    Raafat, A M; Hofseth, L J; Haslam, S Z

    2001-02-01

    The aim of the study was to analyze the proliferative response of the normal mammary gland to combination hormone replacement therapy with estrogen and progesterone in a murine model of early versus late postmenopausal states. Ovariectomized mice were injected daily for up to 56 days with estrogen plus progesterone, starting at either 1 or 5 weeks after ovariectomy to simulate early and late menopausal periods, respectively. At various times after treatment, proliferation was analyzed by deoxyribonucleic acid histoautoradiography and whole-mount preparations. The induction of progesterone receptor by estrogen was also analyzed. To distinguish between estrogen- and progesterone-specific responses, we tested the effects of the antiprogesterone mifepristone (RU 486) and the antiestrogen ICI 182,780. The acute response to estrogen-progesterone therapy in the early postmenopausal period resulted in duct-end enlargement, ductal side branching, alveolar bud formation, and a 100-fold increase in epithelial cell proliferation. This was caused by the dominant effect of progesterone acting through the progesterone receptor. In the late postmenopausal period the acute response produced only duct-end enlargement; the 100-fold increase in epithelial cell proliferation resulted from the dominant effect of estrogen. After long-term treatment, both early and late postmenopausal glands exhibited similar morphologic features and a 9-fold higher steady-state proliferation rate than was found in control-treated groups. Starting combined estrogen and progesterone hormone replacement therapy in either early or late postmenopause produced a persistent, steady-state 9-fold increase in epithelial cell proliferation, which could be a contributing factor to increased breast cancer risk. The acute response in the late postmenopausal period mimics the hormonal response of the pubertal mammary gland, which in rodents is the stage most susceptible to carcinogen-induced mammary tumorigenesis

  12. The effects of progesterone on the alpha2-adrenergic receptor subtypes in late-pregnant uterine contractions in vitro.

    Science.gov (United States)

    Hajagos-Tóth, Judit; Bóta, Judit; Ducza, Eszter; Samavati, Reza; Borsodi, Anna; Benyhe, Sándor; Gáspár, Róbert

    2016-06-14

    The adrenergic system and progesterone play major roles in the control of the uterine function. Our aims were to clarify the changes in function and expression of the α2-adrenergic receptor (AR) subtypes after progesterone pretreatment in late pregnancy. Sprague Dawley rats from pregnancy day 15 were treated with progesterone for 7 days. The myometrial expressions of the α2-AR subtypes were determined by RT-PCR and Western blot analysis. In vitro contractions were stimulated with (-)-noradrenaline, and its effect was modified with the selective antagonists BRL 44408 (α2A), ARC 239 (α2B/C) and spiroxatrine (α2A). The accumulation of myometrial cAMP was also measured. The activated G-protein level was investigated via GTPγS binding assays. Progesterone pretreatment decreased the contractile effect of (-)-noradrenaline through the α2-ARs. The most significant reduction was found through the α2B-ARs. The mRNA of all of the α2-AR subtypes was increased. Progesterone pretreatment increased the myometrial cAMP level in the presence of BRL 44408 (p < 0.001), spiroxatrine (p < 0.001) or the spiroxatrine + BRL 44408 combination (p < 0.05). Progesterone pretreatment increased the G-protein-activating effect of (-)-noradrenaline in the presence of the spiroxatrine + BRL 44408 combination. The expression of the α2-AR subtypes is progesterone-sensitive. It decreases the contractile response of (-)-noradrenaline through the α2B-AR subtype, blocks the function of α2A-AR subtype and alters the G protein coupling of these receptors, promoting a Gs-dependent pathway. A combination of α2C-AR agonists and α2B-AR antagonists with progesterone could be considered for the treatment or prevention of preterm birth.

  13. Isotope-dilution TurboFlow-LC-MS/MS method for simultaneous quantification of ten steroid metabolites in serum

    DEFF Research Database (Denmark)

    Søeborg, Tue; Frederiksen, Hanne; Johannsen, Trine Holm

    2017-01-01

    An isotope-dilution TurboFlow-LC-MS/MS method for simultaneous quantification of the ten steroid metabolites dehydroepiandrosterone sulfate (DHEAS), progesterone, 17α-hydroxyprogesterone (17-OHP), Δ4-androstenedione (Adione), corticosterone, 11-deoxycortisol, cortisol, cortisone, testosterone (T)...

  14. Plasma urea nitrogen and progesterone concentrations and follicular dynamics in ewes fed proteins of different degradability

    Directory of Open Access Journals (Sweden)

    Gustavo Bianchi Lazarin

    2012-07-01

    Full Text Available The effects of overfeeding with protein of different degradability on body condition, plasma urea nitrogen and progesterone concentrations, ovulation number and follicular dynamics were assessed in Santa Ines ewes. Twelve ewes were assigned to a randomized block design according to body weight and received overfeeding with soybean meal or with corn gluten meal or maintenance diet for 28 days before ovulation and during the next estrous cycle. Blood samples were taken on days 7, 14, 21, and 28 after the beginning of treatments for analysis of plasma urea nitrogen and on days 3, 6, 9, 12, and 15 into the estrous cycle for analysis of plasma urea nitrogen and progesterone. Follicular dynamics was monitored daily by ultrasound during one estrous cycle. Dry matter and crude protein intake, weight gain, plasma urea nitrogen concentration before ovulation, number of ovulations, diameter of the largest follicle of the 1st and of the 2nd waves and the growth rate of the largest follicle of the 1st wave were higher in the ewes that received overfeeding. The growth rate of the largest follicle of the 3rd wave was higher in the ewes fed maintenance diet. The back fat thickness, plasma urea nitrogen before ovulation and progesterone concentrations, diameter of the largest follicle of the 2nd wave and growth rate of the largest follicle of the 3rd wave were higher in ewes that received overfeeding with soybean meal. The growth rate of the largest follicle of the 1st wave was higher in ewes that received overfeeding with corn gluten meal. Overfeeding with protein-rich feeds may increase the ovulation number and with soybean meal, it may be effective in increasing plasma progesterone concentration in ewes.

  15. Estradiol and progesterone modulate spontaneous sleep patterns and recovery from sleep deprivation in ovariectomized rats.

    Science.gov (United States)

    Deurveilher, Samüel; Rusak, Benjamin; Semba, Kazue

    2009-07-01

    Women undergo hormonal changes both naturally during their lives and as a result of sex hormone treatments. The objective of this study was to gain more knowledge about how these hormones affect sleep and responses to sleep loss. Rats were ovariectomized and implanted subcutaneously with Silastic capsules containing oil vehicle, 17 beta-estradiol and/or progesterone. After 2 weeks, sleep/wake states were recorded during a 24-h baseline period, 6 h of total sleep deprivation induced by gentle handling during the light phase, and an 18-h recovery period. At baseline and particularly in the dark phase, ovariectomized rats treated with estradiol or estradiol plus progesterone spent more time awake at the expense of non-rapid eye movement sleep (NREMS) and/or REMS, whereas those given progesterone alone spent less time in REMS than ovariectomized rats receiving no hormones. Following sleep deprivation, all rats showed rebound increases in NREMS and REMS, but the relative increase in REMS was larger in females receiving hormones, especially high estradiol. In contrast, the normal increase in NREMS EEG delta power (an index of NREMS intensity) during recovery was attenuated by all hormone treatments. Estradiol promotes arousal in the active phase in sleep-satiated rats, but after sleep loss, both estradiol and progesterone selectively facilitate REMS rebound while reducing NREMS intensity. These results indicate that effects of ovarian hormones on recovery sleep differ from those on spontaneous sleep. The hormonal modulation of recovery sleep architecture may affect recovery of sleep related functions after sleep loss.

  16. Vitamin D deficiency reduces the benefits of progesterone treatment after brain injury in aged rats

    OpenAIRE

    Cekic, Milos; Cutler, Sarah M.; VanLandingham, Jacob W.; Stein, Donald G.

    2009-01-01

    Administration of the neurosteroid progesterone (PROG) has been shown to be beneficial in a number of brain injury models and in two recent clinical trials. Given widespread vitamin D deficiency and increasing traumatic brain injuries (TBIs) in the elderly, we investigated the interaction of vitamin D deficiency and PROG with cortical contusion injury in aged rats. Vitamin D deficient (VitD-deficient) animals showed elevated inflammatory proteins (TNFα, IL-1β, IL-6, NFκB p65) in the brain eve...

  17. Progesterone levels and follicular dynamic during holstein cows postpartum under low tropic conditions in Colombia

    Directory of Open Access Journals (Sweden)

    Carolina Pinzón S.

    2005-05-01

    Full Text Available Thirteen Holstein cows were selected at random and followed, every three days, from the 7th day postpartum until they got pregnant again or day 120 postpartum. Ovarian activity was determined through use of dynamic follicular ultrasounds and the measurement of progesterone levels (RIA. The intervals: delivery first estrus observed, first insemination, first ovulation, first rise in progesterone (>1ng/ml and first dominant follicle were 67.3, 70.3, 27, 36 and 26 days respectively. The conception rate at first insemination was 54.4%. The patterns of follicular growth were inconsistent during the first 15 days postpartum. Some cows showed inactive ovaries and others showed follicles with diameters over 10mm. 72.6% of the cows had “silent” estrous cycles with a luteal phase shorter than those with estrus behavior (12 vs. 15 days and lower progesterone concentration at day 15 ( 1.994 vs. 3.3873 ng/ml. Earlier luteal activity (day 3 was observed in pregnant cows than in open cows (day 6. Pregnant cows had higher progesterone levels at day 15 (over 3 ng/ml while open cows levels went down gradually revealing early luteolysis. Results show that the beginning of postpartum ovarian activity (follicular and hormonal dynamic is not determined by the first estrous behavior. Use of RIA is a tool to detect where in the cycle is the subject animal when there are no external signs of estrus. The delay in reproductive activity, as evaluated based the wide range of open days and the number of services per pregnancy, is not due to a lack of early ovarian activity. It is necessary to analyze together other factors, such as productive pressure and nutritional problems that could be affecting reproductive efficiency in future investigations.

  18. Kadar Estradiol dan Progesteron Serum, Tampilan Vulva dan Sitologi Apus Vagina Kambing Bligon Selama Siklus Birahi

    Directory of Open Access Journals (Sweden)

    Irkham Widiyono

    2012-11-01

    Full Text Available A study was carried out to determine the serum estradiol and progesterone concentration, vulvaappearance, and vaginal cytology during estrous cycle in bligon goat. Four female non pregnant bligongoats (Indonesian indigenous were used in this research. They were clinically healthy and showed normalestrous cycle. Estrous state was examined by using biological method. When the animals showed acceptanceto be mounted by a buck, they were confirmed as the first day of estrous cycle (estrous phase. Collectionof blood sample, preparation of vaginal smears, and measurement of some physical genital parameterswere conducted by standard veterinary clinical methods at day 11, day between 3-5, day between 6-16, andday between 17-19 of estrous cycle. Enzyme linked immunosorbent assay (ELISA was used to determineserum progesterone and estradiol concentrations. Mean difference of each parameter was analyzed byanalyses of variance (Anova, followed by Tuckey HSD. The serum estradiol concentration ranged between211.25-247.77 pg/ml. Peak of the estradiol was occurred at the first day of estrous phase, namely 247.77pg/ml and to decrease at day 3-16. The serum progesterone concentration was at the level of 0.21-0.70 ng/ml and showed a significant increase at day 6-16 (p<0.05. The specific physical genital changes (swellingvulva, reddish mucous membrane of vulva, and excretion of viscous transparent vaginal discharge wereidentified as the animals were at the estrous phase. Composition of exfoliative vaginal cytology did notshow any specific and consistent changes throughout the estrous cycle. Superficial and intermediate cellswere very dominant (>60% during estrous cycle. In conclusion, serum estradiol, progesterone, the vulvaappearance combined with sexual receptivity could be a good estrous predictor for female cycling bligongoat.

  19. Comparison of neonatal outcomes following progesterone use during ovarian stimulation with frozen-thawed embryo transfer

    OpenAIRE

    Zhu, Xiuxian; Ye, Hongjuan; Fu, Yonglun

    2017-01-01

    Progesterone soft capsules (brand name: Utrogestan) were demonstrated to be an effective oral alternative to prevent premature LH surges both in normal-ovulatory and polycystic ovarian syndrome (PCOS) patients. However, its safety in terms of neonatal outcomes is unclear. To evaluate whether Utrogestan use increase the risk of adverse neonatal outcomes compared with short protocol in patients undergoing IVF/ICSI treatments in combination with frozen-thawed embryo transfer (FET), we performed ...

  20. Effect of Progesterone on Latent Phase Prolongation in Patients With Preterm Premature Rupture of Membranes

    Directory of Open Access Journals (Sweden)

    Fatemeh Abdali

    2018-01-01

    Full Text Available Preterm premature rupture of membranes (PPROM is a condition leading to an increased risk of maternal and neonatal morbidity and mortality in pregnant women. To prevent this complication, some studies have proposed using prophylactic progesterone. However, due to lack of sufficient relevant data, there is still need for further studies in this regard. This study was performed to determine the effect of rectal progesterone on the latent phase and maternal and neonatal outcome variables in females with PPROM. During the present randomized clinical trial study (IRCT201512077676N4, a total of 120 patients with PPROM at pregnancy ages between 26 and 32 weeks were randomly assigned to 2 equal intervention and control groups. In the intervention group, progesterone suppositories (400 mg per night were administered until delivery or completion of the 34th gestational week and was compared with placebo effect in control group. The latent phase and maternal and neonatal outcome variables were compared between the two groups. The mean age of patients was 29.56±5.66 (19-42 and 29.88±5.57 (17-40 years in the intervention and control group, respectively. The two groups were almost identical in the confounding factors. The median latent phase was 8.5 days in the intervention group vs. 5 days in the control group in the 28th-30th weeks of gestation, which was significantly higher in the intervention group (P=0.001. Among maternal and neonatal outcome variables, only the mean birth-weight was significantly higher in the intervention group than that in the controls (1609.92±417.28 gr vs. 1452.03±342.35 gr, P=0.03. Administration of progesterone suppository in patients with PPROM at gestational ages of 28 to 30 weeks is effective in elongating the latent phase and increasing birth-weight with no significant complications.

  1. Effect of steroid hormones, estrogen and progesterone, on epithelial mesenchymal transition in ovarian cancer development.

    Science.gov (United States)

    Jeon, So-Ye; Hwang, Kyung-A; Choi, Kyung-Chul

    2016-04-01

    As the primary female sex steroid hormones, estrogens and progesterone play important roles to regulate growth, differentiation, and function of a broad range of target tissues in the human body and maintain the function of female reproductive tissues. Ovarian cancer is the most cause of cancer death in gynecological malignancy. Despite enormous outcomes in the understanding of ovarian cancer pathology, this disease has resulted in poor survival rates since most patients are asymptomatic until the disease has been metastasized. The exact molecular events leading to metastasis of ovarian tumor cells have not yet been well elucidated, although it is recognized that the acquisition of capacity for migration and invasiveness would be a necessary prerequisite. During metastasis, epithelial-mesenchymal transition (EMT) is an important process, in which epithelial cells lose their intracellular adhesion and cell polarity and acquire increased motility and invasive properties to become mesenchymal like cells. The process of cancer cells to undergo EMT is regulated through the up- and down- regulation of a multiple cellular markers and signaling proteins. In this review, we focused the roles of women sex steroid hormones, estrogen and progesterone, in ovarian cancer, especially the ovarian cancer undergoing EMT and metastatic process. All things considered, we may suggest that progesterone is a potent hormone which inhibits the growth of human ovarian cancer cells and development to metastasis whereas estrogen may act as a risk factor of ovarian cancer progression and that progesterone therapy may be an alternative clinically effective tool for the treatment of human ovarian cancer. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. Identification and partial characterization of cytosolic progesterone-binding sites in the filamentous fungus Rhizopus nigricans.

    Science.gov (United States)

    Lenasi, H; Hudnik-Plevnik, T

    1996-06-01

    Progesterone and some other steroids have been shown to induce a steroid 11alpha-hydroxylating enzyme system requiring cytochrome P450 in the filamentous fungus Rhizopus nigricans. In the present work, we attempted to find out whether the mycelial cytosol contained progesterone-binding sites (PBS) which could function as receptors for P450-inducing steroids and might, therefore, be included in the induction process. Two types of constitutive PBS, PBS-I and PBS-II, were identified in the cytosol pretreated with dextran-coated charcoal which removed the endogenous ligand. The protein nature of these binding activities was indicated by their susceptibility to trypsin and proteinase K digestion, heat denaturation, and their resistance to DNase. Progesterone binding was rapid, the maximal level being reached after 45 min of incubation at 22 degrees C. At this temperature, dissociation of progesterone from PBS-I proceeded with a t1/2 of 17 min and that from PBS-II with a t1/2 of 133 min. The apparent Kd of PBS-I determined by Scatchard analysis was 2.1-7.0 x 10(-9)M, and Bmax 36-218 fmol/mg protein. Bmax for PBS-II was >400 fmol/mg protein, whereas the value of Kd could not be determined accurately due to the sigmoidal nature of the association kinetics. The biological role of PBS-I in transcriptional regulation is suggested by the observation that this receptor-like protein contains a functional DNA-binding domain. A specific function of PBS-I in the induction of 11alpha-hydroxylase seems to be, however, questionable because of poor correlation between the affinity and the inducing capability of corresponding steroids.

  3. The progesterone level, leukocyte count and disgust sensitivity across the menstrual cycle.

    Science.gov (United States)

    Żelaźniewicz, Agnieszka; Borkowska, Barbara; Nowak, Judyta; Pawłowski, Bogusław

    2016-07-01

    According to the compensatory prophylaxis hypothesis, women in the luteal phase, characterized by a high progesterone level, which suppresses various mechanisms of immune response, should exhibit higher disgust sensitivity, compared to the follicular phase. In this study we test the hypothesis on the compensatory role of disgust sensitivity at the luteal phase of the menstrual cycle, when immune functions are expected to change due to a rise in progesterone level. Disgust sensitivity, progesterone level (P) and white blood cell count (WBC), a general marker of immunocompetence, were measured in 30 healthy women of reproductive age. Disgust sensitivity was evaluated with: 1) Disgust Scale Revised (DS-R) containing three subscales: Core Disgust, Animal Reminder and Contamination Disgust, 2) Pathogen Disgust and Moral Disgust domains of the Three-Domain Disgust Scale. Measurements were conducted twice - in menstruation (the lowest P) and in the mid-luteal phase (the highest P). The results were analyzed longitudinally and using cross-sectional comparisons. Progesterone level, WBC count, and the level of disgust sensitivity in Animal Domain were higher in the mid-luteal phase comparing to menstruation. The level of disgust sensitivity (DS-R score, Animal, Contamination, Pathogen Disgust) correlated only with P (not WBC) and only in the mid-luteal phase (not in menstruation) in between-subjects comparisons. On the base of these results, we hypothesize that the level of disgust sensitivity in the whole menstrual cycle of a woman is "adjusted" to the luteal phase with the highest P level i.e. when immunosuppression is the greatest. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Estrogen- and progesterone-mediated structural neuroplasticity in women: evidence from neuroimaging

    OpenAIRE

    Catenaccio, Eva; Mu, Weiya; Lipton, Michael L.

    2016-01-01

    There is substantial evidence that the ovarian sex hormones, estrogen and progesterone, which vary considerably over the course of the human female lifetime, contribute to changes in brain structure and function. This structured, quantitative literature reviews aims to summarize neuroimaging literature addressing physiological variation in brain macro- and microstructure across an array of hormonal transitions including the menstrual cycle, use of hormonal contraceptives, pregnancy, and menop...

  5. ESR1 and PGR polymorphisms are associated with estrogen and progesterone receptor expression in breast tumors

    OpenAIRE

    Hertz, Daniel L.; Henry, N. Lynn; Kidwell, Kelley M.; Thomas, Dafydd; Goddard, Audrey; Azzouz, Faouzi; Speth, Kelly; Li, Lang; Banerjee, Mousumi; Thibert, Jacklyn N; Kleer, Celina G.; Stearns, Vered; Hayes, Daniel F.; Skaar, Todd C.; Rae, James M.

    2016-01-01

    Hormone receptor-positive (HR+) breast cancers express the estrogen (ERα) and/or progesterone (PgR) receptors. Inherited single nucleotide polymorphisms (SNPs) in ESR1, the gene encoding ERα, have been reported to predict tamoxifen effectiveness. We hypothesized that these associations could be attributed to altered tumor gene/protein expression of ESR1/ERα and that SNPs in the PGR gene predict tumor PGR/PgR expression. Formalin-fixed paraffin-embedded breast cancer tumor specimens were analy...

  6. Prediction of Cortisol and Progesterone Concentrations in Cow Hair Using Near-Infrared Reflectance Spectroscopy (NIRS).

    Science.gov (United States)

    Tallo-Parra, Oriol; Albanell, Elena; Carbajal, Annais; Monclús, Laura; Manteca, Xavier; Lopez-Bejar, Manel

    2017-08-01

    Concentrations of different steroid hormones have been used in cows as a measure of adrenal or gonadal activity and, thus, as indicators of stress or reproductive state. Detecting cortisol and progesterone in cow hair provides a long-term integrative value of retrospective adrenal or gonadal/placental activity, respectively. Current techniques for steroid detection require a hormone-extraction procedure that involves time, several types of equipment, management of reagents, and some assay procedures (which can also be time-consuming and can destroy the samples). In contrast, near-infrared reflectance spectroscopy (NIRS) is a multi-component predictor technique, characterized as rapid, nondestructive for the sample, and reagent-free. However, as a predictor technique, NIRS needs to be calibrated and validated for each matrix, hormone, and species. The main objective of this study was to evaluate the predictive value of the NIRS technique for hair cortisol and progesterone quantification in cows by using specific enzyme immunoassay as a reference method. Hair samples from 52 adult Friesian lactating cows from a commercial dairy farm were used. Reflectance spectra of hair samples were determined with a NIR reflectance spectrophotometer before and after trimming them. Although similar results were obtained, a slightly better relationship between the reference data and NIRS predicted values was found using trimmed samples. Near infrared reflectance spectroscopy demonstrated its ability to predict cortisol and progesterone concentrations with certain accuracy (R(2 )= 0.90 for cortisol and R(2 )= 0.87 for progesterone). Although NIRS is far from being a complete alternative to current methodologies, the proposed equations can offer screening capability. Considering the advantages of both fields, our results open the possibility for future work on the combination of hair steroid measurement and NIRS methodology.

  7. Sex differences in attenuation of nicotine reinstatement after individual and combined treatments of progesterone and varenicline

    OpenAIRE

    Swalve, Natashia; Smethells, John R.; Carroll, Marilyn E.

    2016-01-01

    Tobacco use is the largest cause of preventable mortality in the western world. Even after treatment, relapse rates for tobacco are high, and more effective pharmacological treatments are needed. Progesterone (PRO), a female hormone used in contraceptives, reduces stimulant use but its effects on tobacco addiction are unknown. Varenicline (VAR) is a commonly used medication that reduces tobacco use. The present study examined sex differences in the individual vs. combined effects of PRO and V...

  8. Sex differences in reinstatement of cocaine-seeking with combination treatments of progesterone and atomoxetine

    OpenAIRE

    Swalve, Natashia; Smethells, John R.; Zlebnik, Natalie E.; Carroll, Marilyn E.

    2016-01-01

    Two repurposed medications have been proposed to treat cocaine abuse. Progesterone, a gonadal hormone, and atomoxetine, a medication commonly used to treat attention deficit/hyperactivity disorder, have both been separately shown to reduce cocaine self-administration and reinstatement (i.e. relapse). The goal of the present study was to examine sex differences in the individual effects of PRO and ATO as well as the combination PRO+ATO treatment on cocaine (COC), caffeine (CAF), and/or cue-pri...

  9. Progesterone Induces Mucosal Immunity in a Rodent Model of Human Taeniosis by Taenia solium

    OpenAIRE

    Escobedo, Galileo; Camacho-Arroyo, Ignacio; Nava-Luna, Paul; Olivos, Alfonso; P?rez-Torres, Armando; Leon-Cabrera, Sonia; Carrero, J.C.; Morales-Montor, Jorge

    2011-01-01

    More than one quarter of human world's population is exposed to intestinal helminth parasites. The Taenia solium tapeworm carrier is the main risk factor in the transmission of both human neurocysticercosis and porcine cysticercosis. Sex steroids play an important role during T. solium infection, particularly progesterone has been proposed as a key immunomodulatory hormone involved in susceptibility to human taeniosis in woman and cysticercosis in pregnant pigs. Thus, we evaluated the effect ...

  10. HIV protease inhibitor use during pregnancy is associated with decreased progesterone levels, suggesting a potential mechanism contributing to fetal growth restriction.

    Science.gov (United States)

    Papp, Eszter; Mohammadi, Hakimeh; Loutfy, Mona R; Yudin, Mark H; Murphy, Kellie E; Walmsley, Sharon L; Shah, Rajiv; MacGillivray, Jay; Silverman, Michael; Serghides, Lena

    2015-01-01

    Protease inhibitor (PI)-based combination antiretroviral therapy (cART) is administered during pregnancy to prevent perinatal human immunodeficiency virus (HIV) transmission. However, PI use has been associated with adverse birth outcomes, including preterm delivery and small-for-gestational-age (SGA) births. The mechanisms underlying these outcomes are unknown. We hypothesized that PIs contribute to these adverse events by altering progesterone levels. PI effects on trophoblast progesterone production were assessed in vitro. A mouse pregnancy model was used to assess the impact of PI-based cART on pregnancy outcomes and progesterone levels in vivo. Progesterone levels were assessed in plasma specimens from 27 HIV-infected and 17 HIV-uninfected pregnant women. PIs (ritonavir, lopinavir, and atazanavir) but not nucleoside reverse transcriptase inhibitors (NRTIs) or nonnucleoside reverse transcriptase inhibitors reduced trophoblast progesterone production in vitro. In pregnant mice, PI-based cART but not dual-NRTI therapy was associated with significantly lower progesterone levels that directly correlated with fetal weight. Progesterone supplementation resulted in a significant improvement in fetal weight. We observed lower progesterone levels and smaller infants in HIV-infected women receiving PI-based cART, compared with the control group. In HIV-infected women, progesterone levels correlated significantly with birth weight percentile. Our data suggest that PI use in pregnancy may lead to lower progesterone levels that could contribute to adverse birth outcomes. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.

  11. Oxidative stress effect on progesterone-induced blocking factor (PIBF) binding to PIBF-receptor in lymphocytes.

    Science.gov (United States)

    de la Haba, Carlos; Palacio, José R; Palkovics, Tamas; Szekeres-Barthó, Júlia; Morros, Antoni; Martínez, Paz

    2014-01-01

    Receptor-ligand binding is an essential interaction for biological function. Oxidative stress can modify receptors and/or membrane lipid dynamics, thus altering cell physiological functions. The aim of this study is to analyze how oxidative stress may alter receptor-ligand binding and lipid domain distribution in the case of progesterone-induced blocking factor/progesterone-induced blocking factor-receptor. For membrane fluidity regionalization analysis of MEC-1 lymphocytes, two-photon microscopy was used in individual living cells. Lymphocytes were also double stained with AlexaFluor647/progesterone-induced blocking factor and Laurdan to evaluate -induced blocking factor/progesterone-induced blocking factor-receptor distribution in the different membrane domains, under oxidative stress. A new procedure has been developed which quantitatively analyzes the regionalization of a membrane receptor among the lipid domains of different fluidity in the plasma membrane. We have been able to establish a new tool which detects and evaluates lipid raft clustering from two-photon microscopy images of individual living cells. We show that binding of progesterone-induced blocking factor to progesterone-induced blocking factor-receptor causes a rigidification of plasma membrane which is related to an increase of lipid raft clustering. However, this clustering is inhibited under oxidative stress conditions. In conclusion, oxidative stress decreases membrane fluidity, impairs receptor-ligand binding and reduces lipid raft clustering. © 2013.

  12. DIF-1, an anti-tumor substance found in Dictyostelium discoideum, inhibits progesterone-induced oocyte maturation in Xenopus laevis.

    Science.gov (United States)

    Kubohara, Yuzuru; Hanaoka, Yoichi; Akaishi, Emi; Kobayashi, Hisae; Maeda, Mineko; Hosaka, Kohei

    2003-01-24

    Differentiation-inducing factor-1 (DIF-1; 1-(3,5-dichloro-2,6-dihydroxy-4-methoxyphenyl)hexan-1-one) is a putative morphogen that induces stalk-cell formation in the cellular slime mold Dictyostelium discoideum. DIF-1 has previously been shown to suppress cell growth in mammalian cells. In this study, we examined the effects of DIF-1 on the progesterone-induced germinal vesicle breakdown in Xenopus laevis, which is thought to be mediated by a decrease in intracellular cAMP and the subsequent activation of mitogen-activated protein kinase (MAPK) and maturation-promoting factor, a complex of cdc2 and cyclin B, which regulates germinal vesicle breakdown. DIF-1 at 10-40 microM inhibited progesterone-induced germinal vesicle breakdown in de-folliculated oocytes in a dose-dependent manner. Progesterone-induced cdc2 activation, MAPK activation, and c-Mos accumulation were inhibited by DIF-1. Furthermore, DIF-1 was found to inhibit the progesterone-induced cAMP decrease in the oocytes. These results indicate that DIF-1 inhibits progesterone-induced germinal vesicle breakdown possibly by blocking the progesterone-induced decrease in [cAMP](i) and the subsequent events in Xenopus oocytes.

  13. [Aspects of progesterone receptor (PR) activity regulation - impact on breast cancer progression].

    Science.gov (United States)

    Piasecka, Dominika; Składanowski, Andrzej C; Kordek, Radzisław; Romańska, Hanna M; Sądej, Rafał

    2015-01-01

    Progesterone receptor (PR) and its specific ligand play a key role in development and physiology of mammary gland. The role of PR in initiation and progression of breast carcinoma (BCa) is unquestionable, although molecular mechanism of PR action is complex and not fully understood. It is known that increased risk of breast cancer is associated with progestin-based (synthetic ligands of progesterone) hormonal contraception or hormone replacement therapies. It is estimated that ER/PR-positive tumours represent approximately 50-70% of all BCa cases, and the loss of PR is associated with resistance to hormonal therapy and increased tumour invasiveness. In classical, genomic signalling pathway cytoplasmic PR, following ligand binding, translocates to the nucleus and regulates expression of genes with the PRE sequence. PR is also involved in a large number of alternative, non-genomic signalling cascades, e.g. PR is able to activate MAPK and PI3K/AKT pathways, which leads to regulation of gene expression. The cross-talk between PR and Growth Factors Receptors (GFR) results in progesterone-independent activation of PR as well as PR-regulated GFR expression and activation. Growth factors signalling promotes formation of a pool of hypersensitive PR responsive to even very low ligand concentration. Transcriptional activity of PR as well as its dynamic impact on processes such as cell migration and adhesion are crucial for BCa progression. Further studies of multifaceted mechanisms of PR action may contribute to new PR-targeting therapeutic strategies for breast cancer patients.

  14. REPRODUCTIVE EFFICIENCY AND PROGESTERONE PROFILE FROM PARTURITION TO PARTURITION IN DW ARF GOAT

    Directory of Open Access Journals (Sweden)

    Shahnaz A. Khanum, M. Hussain, M. Ali, S. H, M. Naqvi, R. Kausar and A. M. Cheema1

    2001-09-01

    Full Text Available A study was undertaken to look into the reproductive performance of female Dwarf goat. The serum progesterone profile was used to monitor various reproductive parameters including length of postpartum period, the resumption of cyclicity, gestation period, pre-partum period, parturition, litter size and kidding interval. Most of the animals conceived within 20-65 days of postpartum period. During gestation period, higher levels of progesterone were maintained with wide variations falling in the range of3-13 ng/ml. Notable feature was the fluctuation of progesterone level in the higher limits (> 3 ng/ml throughout the gestation. However, a few days before parturition a decline was noticed in all the animals. This decline started at 6 + 0.4 days of prepartum and dropped to the lowest level of 0.1 ng/ml after the completion of parturition process. The length of gestation period was found to be 145.5+1.1 days. A very short kidding interval (204 + 19 days and a big litter size was observed. All the parturitions were normal and a considerable weight gain (8.2 + 0.3 kg was recorded during pregnancy. The initial birth weight of kids was 2.1 + 0.53 kg. All the animals of the lot conceived at first or second oestrous, indicating the high prolificacy of the breed.

  15. Progesterone increases glomerular filtration rate, urinary kallikrein excretion and uric acid clearance in normal women.

    Science.gov (United States)

    Atallah, A N; Guimarães, J A; Gebara, M; Sustovich, D R; Martinez, T R; Camano, L

    1988-01-01

    In pregnancy there is a rise in glomerular filtration rate (GFR), plasma aldosterone levels, uric acid clearance and urinary kallikrein excretion. In toxemia all the above parameters tend to decrease. Progesterone has a diuretic effect which is usually related to aldosterone antagonism. We administered progesterone to normal women and observed that GFR, uric acid clearance and kallikrein excretion increased significantly, GFR from 103.0 +/- 13.7 ml/min to 118.0 +/- 18.0 ml/min (P less than 0.01), uric acid clearance from 9.0 +/- 3.6 ml/min to 14.3 +/- 4.0 ml/min (P less than 0.01), and urinary kallikrein excretion from 165 +/- 156 mU to 432 +/- 220 mU (P less than 0.01). Natriuresis and potassium excretion also increased from 15.9 +/- 6.4 mEq to 33.4 +/- 10.9 mEq (P less than 0.01) and from 7.6 +/- 2.7 mEq to 14.0 +/- 5.4 mEq, (P less than 0.01), respectively, suggesting that in this situation aldosterone antagonism is not relevant to explain the diuretic effects of progesterone.

  16. Proliferative and Invasive Effects of Progesterone-Induced Blocking Factor in Human Glioblastoma Cells

    Directory of Open Access Journals (Sweden)

    Araceli Gutiérrez-Rodríguez

    2017-01-01

    Full Text Available Progesterone-induced blocking factor (PIBF is a progesterone (P4 regulated protein expressed in different types of high proliferative cells including astrocytomas, the most frequent and aggressive brain tumors. It has been shown that PIBF increases the number of human astrocytoma cells. In this work, we evaluated PIBF regulation by P4 and the effects of PIBF on proliferation, migration, and invasion of U87 and U251 cells, both derived from human glioblastomas. PIBF mRNA expression was upregulated by P4 (10 nM from 12 to 24 h. Glioblastoma cells expressed two PIBF isoforms, 90 and 57 kDa. The content of the shorter isoform was increased by P4 at 24 h, while progesterone receptor antagonist RU486 (10 μM blocked this effect. PIBF (100 ng/mL increased the number of U87 cells on days 4 and 5 of treatment and induced cell proliferation on day 4. Wound-healing assays showed that PIBF increased the migration of U87 (12–48 h and U251 (24 and 48 h cells. Transwell invasion assays showed that PIBF augmented the number of invasive cells in both cell lines at 24 h. These data suggest that PIBF promotes proliferation, migration, and invasion of human glioblastoma cells.

  17. Gene expression analysis of endometrium reveals progesterone resistance and candidate susceptibility genes in women with endometriosis.

    Science.gov (United States)

    Burney, Richard O; Talbi, Said; Hamilton, Amy E; Vo, Kim Chi; Nyegaard, Mette; Nezhat, Camran R; Lessey, Bruce A; Giudice, Linda C

    2007-08-01

    The identification of molecular differences in the endometrium of women with endometriosis is an important step toward understanding the pathogenesis of this condition and toward developing novel strategies for the treatment of associated infertility and pain. In this study, we conducted global gene expression analysis of endometrium from women with and without moderate/severe stage endometriosis and compared the gene expression signatures across various phases of the menstrual cycle. The transcriptome analysis revealed molecular dysregulation of the proliferative-to-secretory transition in endometrium of women with endometriosis. Paralleled gene expression analysis of endometrial specimens obtained during the early secretory phase demonstrated a signature of enhanced cellular survival and persistent expression of genes involved in DNA synthesis and cellular mitosis in the setting of endometriosis. Comparative gene expression analysis of progesterone-regulated genes in secretory phase endometrium confirmed the observation of attenuated progesterone response. Additionally, interesting candidate susceptibility genes were identified that may be associated with this disorder, including FOXO1A, MIG6, and CYP26A1. Collectively these findings provide a framework for further investigations on causality and mechanisms underlying attenuated progesterone response in endometrium of women with endometriosis.

  18. Radio-immunoassay of salivary progesterone for monitoring ovarian function in female infertility

    Energy Technology Data Exchange (ETDEWEB)

    Luisi, M.; Franchi, F.; Bianchi, S.; Gravina, G.; Podesta, A.

    1987-01-01

    Fifty-two women, aged from 25 to 41 years, with infertility due to chronic anovulation were admitted to the study together with 36 age-matched controls with proven ovulatory cycles. Paired plasma (3 ml) and whole unstimulated saliva (10 ml) samples were collected over a 30 day period, starting from the first day of a menstrual bleeding, in patients, and throughout the menstrual cycle, in controls. Salivary progesterone levels, measured in women with infertility, ranged from undetectable values to 16 pmol/l during the first, and from 36 to 98 pmol/l during the second half of the monitoring period. In eugonadal women the steroid levels ranged from 34 to 46 pmol/I and from 96 to 780 pmol/l during the follicular and luteal phases, respectively. The saliva/plasma progesterone ratio ranged from 0.58 to 2.71 p. cent and a good correlation between salivary and plasma levels was found at each time of monitoring. Many (86 p. cent) of patients, which were randomly allocated to a low-or high-dose epimestrol administration schedule, appeared to be sensitive to the drug, achieving, after therapy, salivary progesterone levels which were within the range of controls. Since correct assessment of luteal function in basal conditions and during therapy requires multiple steroid measurements, and since saliva can be obtained by non-invasive techniques, salivary assays represent an attractive alternative to plasma ones for monitoring ovarian activity, also during specific treatment.

  19. The effect of Ramadan fasting on LH, FSH, oestrogen, progesterone and leptin in pregnant women.

    Science.gov (United States)

    Khoshdel, A; Kheiri, S; Hashemi-Dehkordi, E; Nasiri, J; Shabanian-Borujeni, S; Saedi, E

    2014-10-01

    Many pregnant Muslim women fast during Ramadan. Leptin has an important role in the reproductive system and hormones. In this study, FSH, LH, oestrogen, progesterone and leptin were measured in the first, second and fourth week of Ramadan and the second week post-Ramadan, in 30 fasting pregnant women. Data were analysed using repeated measures ANOVA by SPSS. The weight and BMI did not change during the study. A significant change in FSH, oestrogen, progesterone and leptin was observed (p Ramadan. Progesterone increased at the end of Ramadan and the second week after. Oestrogen increased significantly during Ramadan and decreased after Ramadan. A decreasing trend was seen in LH during the Ramadan and 2 weeks after (p Ramadan. We found poor weight gain and hypoleptinaemia in pregnant fasted women during the study. Food restriction in pregnant fasted women during Ramadan may induce poor weight gain during pregnancy. These data confirm that Ramadan fasting by pregnant women may have potential risks during pregnancy. We recommend further study to evaluate long-term effects of Ramadan fasting during pregnancy in different countries with different food habits and traditions, to obtain reliable and documented data.

  20. Progesterone receptor membrane component 1 and its role in ovarian follicle growth

    Directory of Open Access Journals (Sweden)

    John J Peluso

    2013-06-01

    Full Text Available Progesterone (P4 is synthesized in the ovary and acts directly on granulosa cells of developing ovarian follicles to suppress their rate of mitosis and apoptosis. Granulosa cells do not express nuclear progesterone receptor (PGR but rather progesterone receptor membrane component-1 (PGRMC1. PGRMC1 binds P4 and mediates P4’s actions, as evidenced by PGRMC1 siRNA studies. PGRMC1 acts by binding plasminogen activator inhibitor 1 RNA binding protein and regulating gene expression. Specifically, PGRMC1 suppresses some genes that promote cell death (i.e. Bad, Caspase-3, Caspase-4. P4 regulates gene expression in part by inhibiting PGRMC1 binding to Tcf/Lef transcription sites, thereby reducing Tcf/Lef transcriptional activity. Since Tcf/Lef transcription sites are located within the promoters of genes that initiate mitosis and/or apoptosis (i.e. c-jun and c-myc, P4-PGRMC1 mediated suppression of these Tcf/Lef regulated genes could account for P4’s actions. PGRMC1 expression is also altered in women with polycystic ovarian syndrome, premature ovarian failure and infertility. Collectively, these observations support a role for PGRMC1 in regulating human ovarian follicle development.

  1. Daily Fluctuations of Progesterone and Testosterone are Associated with Fibromyalgia Pain Severity.

    Science.gov (United States)

    Schertzinger, Meredith; Wesson-Sides, Kate; Parkitny, Luke; Younger, Jarred

    2017-12-14

    The purpose of this longitudinal blood sampling study was to examine relationships between sex hormones and fibromyalgia pain. Eight women meeting case definition criteria for fibromyalgia provided venous blood samples and reported their fibromyalgia pain severity over 25 consecutive days. All women exhibited normal menstrual cycles and were not taking oral contraceptives. Cortisol, and the sex hormones estradiol, progesterone, and testosterone, were assayed from serum. A linear mixed model was used to determine if fluctuations of sex hormones were associated with changes in pain severity. In the entire sample, day-to-day changes in both progesterone (p = 0.002) and testosterone (p = 0.015) were significantly and inversely correlated with pain severity. There was no relationship between estradiol and pain (p = 0.551) or cortisol and pain (p = 0.633). These results suggest that progesterone and testosterone play a protective role in fibromyalgia pain severity. Sex and other hormones may serve to both increase and decrease fibromyalgia pain severity. Sex hormones fluctuate normally in women with fibromyalgia, but may still contribute to pain severity. Copyright © 2017. Published by Elsevier Inc.

  2. Characterization and ligand identification of a membrane progesterone receptor in fungi: existence of a novel PAQR in Sporothrix schenckii.

    Science.gov (United States)

    Gonzalez-Velazquez, Waleska; Gonzalez-Mendez, Ricardo; Rodriguez-del Valle, Nuri

    2012-09-07

    Adaptive responses in fungi result from the interaction of membrane receptors and extracellular ligands. Many different classes of receptors have been described in eukaryotic cells. Recently a new family of receptors classified as belonging to the progesterone-adiponectin receptor (PAQR) family has been identified. These receptors have the seven transmembrane domains characteristic of G-protein coupled receptors, but their activity has not been associated directly to G proteins. They share sequence similarity to the eubacterial hemolysin III proteins. A new receptor, SsPAQR1 (Sporothrix schenckii progesterone-adiponectinQ receptor1), was identified as interacting with Sporothrix schenckii G protein alpha subunit SSG-2 in a yeast two-hybrid assay. The receptor was identified as a member of the PAQR family. The cDNA sequence revealed a predicted ORF of 1542 bp encoding a 514 amino acids protein with a calculated molecular weight of 57.8 kDa. Protein domain analysis of SsPAQR1 showed the 7 transmembrane domains (TM) characteristic of G protein coupled receptors and the presence of the distinctive motifs that characterize PAQRs. A yeast-based assay specific for PAQRs identified progesterone as the agonist. S. schenckii yeast cells exposed to progesterone (0.50 mM) showed an increase in intracellular levels of 3', 5' cyclic adenosine monophosphate (cAMP) within the first min of incubation with the hormone. Different progesterone concentrations were tested for their effect on the growth of the fungus. Cultures incubated at 35°C did not grow at concentrations of progesterone of 0.05 mM or higher. Cultures incubated at 25°C grew at all concentrations tested (0.01 mM-0.50 mM) with growth decreasing gradually with the increase in progesterone concentration. This work describes a receptor associated with a G protein alpha subunit in S. schenckii belonging to the PAQR family. Progesterone was identified as the ligand. Exposure to progesterone increased the levels of cAMP in

  3. Primate-specific Melanoma Antigen-A11 Regulates Isoform-specific Human Progesterone Receptor-B Transactivation*

    Science.gov (United States)

    Su, Shifeng; Blackwelder, Amanda J.; Grossman, Gail; Minges, John T.; Yuan, Lingwen; Young, Steven L.; Wilson, Elizabeth M.

    2012-01-01

    Progesterone acting through the progesterone receptor (PR) and its coregulators prepares the human endometrium for receptivity to embryo implantation and maintains pregnancy. The menstrual cycle-dependent expression of melanoma antigen-A11 (MAGE-11) in the mid-secretory human endometrium suggested a novel function in human PR signaling. Here we show that MAGE-11 is an isoform-specific coregulator responsible for the greater transcriptional activity of human PR-B relative to PR-A. PR was recruited to progesterone response regions of progesterone-regulated FK506-binding protein 5 (FKBP5) immunophilin and small Ras family G protein cell growth inhibitor RASD1 genes. Expression of MAGE-11 lentivirus shRNA in human endometrial Ishikawa cells expressing PR-B showed that MAGE-11 is required for isoform-specific PR-B up-regulation of FKBP5. In contrast, MAGE-11 was not required for progesterone up-regulation of RASD1 in endometrial cells expressing the PR-A/B heterodimer. Target gene specificity of PR-B depended on the synergistic actions of MAGE-11 and p300 mediated by the unique PR-B NH2-terminal 110LLXXVLXXLL119 motif that interacts with the MAGE-11 F-box region in a phosphorylation- and ubiquitinylation-dependent manner. A progesterone-dependent mechanism is proposed in which MAGE-11 and p300 increase PR-B up-regulation of the FKBP5 gene. MAGE-11 down-regulates PR-B, similar to the effects of progesterone, and interacts with FKBP5 to stabilize a complex with PR-B. We conclude that the coregulator function of MAGE-11 extends to isoform-specific regulation of PR-B during the cyclic development of the human endometrium. PMID:22891251

  4. In-vitro rescue and recovery studies of human melanoma (BLM) cell growth, adhesion and migration functions after treatment with progesterone.

    Science.gov (United States)

    Leder, Douglas C; Brown, Jason R; Ramaraj, Pandurangan

    2015-01-01

    Treatment of human melanoma (BLM) cells for 48 hrs with progesterone resulted in a significant inhibition of cell growth. The mechanism of growth inhibition was due to autophagy and this action of progesterone was not mediated through progesterone receptor. As cells were floating during treatment, adhesion assay was performed, which showed complete loss of adhesion. When cells were allowed to recover after treatment by culturing in growth medium without progesterone, there was recovery in cell growth. Preliminary experiments on adhesion and recovery cell growth prompted us to suppress autophagic lysosomal degradation with 3-methyladenine (3-MA), which resulted in partial rescue of cell growth, adhesion and migration functions. The above experimental design gave rise to two experimental groups viz., progesterone treated and 3-MA rescued. Since, recovery studies also showed improvement in cell growth, progesterone treated and 3-MA rescued groups were allowed to recover on their own for first 48 hrs and then a second 48 hrs. Comparison of in-vitro cell growth, adhesion and migration functions of progesterone treated, 3-MA rescued and recovered human melanoma cells revealed that the recovery of 3-MA rescued cells was better than the recovery of progesterone treated cells in terms of cell growth and adhesion functions. These in-vitro experiments not only provided the scientific basis for epidemiological findings that menstruating females were better protected in melanoma, but also showed the potential of progesterone to act as an anti-cancer agent for melanoma treatment.

  5. Rapidly disintegrating vagina retentive cream suppositories of progesterone: development, patient satisfaction and in vitro/in vivo studies.

    Science.gov (United States)

    Bendas, Ehab Rasmy; Basalious, Emad B

    2016-01-01

    Our objective was to develop novel vagina retentive cream suppositories (VRCS) of progesterone having rapid disintegration and good vaginal retention. VRCS of progesterone were prepared using oil in water (o/w) emulsion of mineral oil or theobroma oil in hard fat and compared with conventional vaginal suppositories (CVS) prepared by hard fat. VRCS formulations were tested for content uniformity, disintegration, melting range, in vitro release and stability studies. The most stable formulation (VRCS I) was subjected to scaling-up manufacturing and patients' satisfaction test. The rapid disintegration, good retentive properties are applicable through the inclusion of emulsified theobroma oil rather than hydrophilic surfactant into the hard fat bases. The release profile of progesterone from VRCS I showed a biphasic pattern due to the formation of progesterone reservoir in the emulsified theobroma oil. All volunteers involved in patients' satisfaction test showed high satisfactory response to the tested formulation (VRCS). The in vivo pharmacokinetic study suggests that VRCS of progesterone provided higher rate and extent of absorption compared to hard fat based suppositories. Our results proposed that emulsified theobroma oil could be promising to solve the problems of poor patients' satisfaction and variability of drug absorption associated with hard fat suppositories.

  6. Progesterone promotes neuronal differentiation of human umbilical cord mesenchymal stem cells in culture conditions that mimic the brain microenvironment★

    Science.gov (United States)

    Wang, Xianying; Wu, Honghai; Xue, Gai; Hou, Yanning

    2012-01-01

    In this study, human umbilical cord mesenchymal stem cells from full-term neonates born by vaginal delivery were cultured in medium containing 150 mg/mL of brain tissue extracts from Sprague-Dawley rats (to mimic the brain microenvironment). Immunocytochemical analysis demonstrated that the cells differentiated into neuron-like cells. To evaluate the effects of progesterone as a neurosteroid on the neuronal differentiation of human umbilical cord mesenchymal stem cells, we cultured the cells in medium containing progesterone (0.1, 1, 10 μM) in addition to brain tissue extracts. Reverse transcription-PCR and flow cytometric analysis of neuron specific enolase-positive cells revealed that the percentages of these cells increased significantly following progesterone treatment, with the optimal progesterone concentration for neuron-like differentiation being 1 μM. These results suggest that progesterone can enhance the neuronal differentiation of human umbilical cord mesenchymal stem cells in culture medium containing brain tissue extracts to mimic the brain microenvironment. PMID:25624820

  7. Effect of feeding level on luteal function and progesterone concentration in the vena cava during early pregnancy in gilts.

    Science.gov (United States)

    Athorn, R Z; Stott, P; Bouwman, E G; Chen, T Y; Kennaway, D J; Langendijk, P

    2013-01-01

    This study assessed the effect of feeding level on progesterone concentration in the caudal vena cava during early pregnancy in gilts. Twenty-four Landrace gilts were allocated to either a high (2.8±0.02) or a low (1.5±0.01 kg day⁻¹) feeding level at Day 0 of pregnancy. Serial blood samples were collected every 15 min for 3 h before and 3 h after feeding on Days 6 and 9 of pregnancy. Embryo survival and development as well as in vitro luteal progesterone production were assessed at Day 10 of pregnancy. Progesterone concentration in the vena cava was pulsatile with gilts on the high feeding level having more pulses compared with Low gilts on Day 9 of pregnancy (Pgilts on the high feeding level (Pgilts compared with 77±3% for Low gilts (P<0.05). No difference in embryo development between the treatments was seen. There was no difference between treatments in in vitro secretion of progesterone by luteal tissue. In conclusion, a high plane of nutrition positively affects progesterone secretion by the ovaries in early pregnancy.

  8. Uterine epithelial morphology and progesterone receptors in a mifepristone-treated viviparous lizard Pseudemoia entrecasteauxii (Squamata: Scincidae) during gestation.

    Science.gov (United States)

    Biazik, Joanna M; Parker, Scott L; Murphy, Christopher R; Thompson, Michael B

    2012-03-01

    Structural and functional changes to the uterus associated with maintenance of pregnancy are controlled primarily by steroid hormones such as progesterone. We tested the hypothesis that progesterone regulates uterine structural changes during pregnancy in the viviparous skink, Pseudemoia entrecasteauxii, by treating pregnant females with the progesterone receptor antagonist mifepristone at different stages of pregnancy. Expression and distribution of progesterone receptor was determined using Western blot and immunohistochemistry. During early pregnancy, mifepristone treatment resulted in altered uterine epithelial cell surface morphology and high embryo mortality, but did not affect females at mid and late stages of pregnancy. Females treated with mifepristone in early pregnancy exhibited abnormal uterine epithelial cell morphology such as lateral blebbing and presence of wide gaps between cells indicating loss of intercellular attachment. Chorioallantoic membranes of the embryo were not affected by mifepristone treatment. Two isoforms (55 kDa and 100 kDa) of progesterone receptor were identified using immunoblots and both isoforms were localized to the nucleus of uterine epithelial cells. The 55 kDa isoform was expressed throughout pregnancy, whereas the 100 kDa isoform was expressed during mid and especially late pregnancy. In P. entrecasteauxii, mifepristone may prevent successful embryo attachment in early pregnancy through its effects on uterine epithelial cells but may have little effect on pregnancy once the maternal-embryo structural relationship is established. © 2011 WILEY PERIODICALS, INC.

  9. Effect of Intrahippocampal Administration of Vitamin C and Progesterone on Learning in a Model of Multiple Sclerosis in Rats

    Directory of Open Access Journals (Sweden)

    Shirin Babri

    2015-03-01

    Full Text Available Purpose: The purpose of this study was to evaluate the effect of intrahippocampal injection of vitamin C and progesterone, alone or in combination, on passive avoidance learning (PAL in multiple sclerosis. Methods: Sixty- three male wistar rats were divided into nine groups (n=7 as following: control (saline, lesion, vitamin C (0.2, 1, 5 mg/kg, progesterone (0.01, 0.1, 1 μg/μl and combination therapy. Lesion was induced by intrahippocampal injection of ethidium bromide. In combination therapy, animals were treated with vitamin C (5 mg/kg plus progesterone (0.01 mg/kg. Animals in experimental groups received different treatments for 7 days, and then all groups were tested for step through latency (STL. Results: Our results showed that intrahippocampal injection of ethidium bromide destroys PAL significantly (p<0.001. Treatment with vitamin C (5mg/kg significantly (p<0.05 improved PAL. Lower doses of progesterone did not affect latency but dose of 1 μg/μl significantly (p<0.05 increased STL. In combination therapy group STL was significantly (p<0.05 more than in the lesion group, although it was not significantly different from the vitamin C group. Conclusion: Based on our results, we concluded that intrahippocampal injection of vitamin C improves memory for PAL, but progesterone alone or in combination with vitamin C had no improving effects on memory.

  10. Effects of environmental stress during pregnancy on maternal and fetal plasma corticosterone and progesterone in the rat

    Energy Technology Data Exchange (ETDEWEB)

    Fleming, D.E.; Rhees, R.W.; Williams, S.R.; Kurth, S.M.

    1986-03-01

    Prenatal stress applied during a presumed critical period (third trimester) for sexual differentiation of the brain has been shown to alter development and influence sexual behavior. This experiment was designed to study the effects of environmental stress (restraint/illumination/heat) on maternal and fetal plasma corticosterone and progesterone titers. These hormones were studied since corticosterone has been shown to alter brain differentiation and progesterone has anti-androgen properties and since the secretion of both from the adrenal cortex is stimulated by ACTH. Plasma corticosterone and progesterone titers of both stressed and control gravid rats and their fetuses were measured on gestational days 18 and 20 by radioimmunoassay. Prenatal stress significantly reduced fetal body weight and fetal adrenal weight. Maternal pituitary weight was significantly increased. Prenatal stress caused a significant elevation in maternal corticosterone and progesterone titers and in fetal corticosterone titers. There was no difference between prenatal stressed and control fetal plasma progesterone levels. These data demonstrate that environmental stress significantly increases adrenal activity beyond that brought about naturally by pregnancy, and therefore may modify sequential hormonal events during fetal development.

  11. Salience of emotional displays of danger and contagion in faces is enhanced when progesterone levels are raised.

    Science.gov (United States)

    Conway, C A; Jones, B C; DeBruine, L M; Welling, L L M; Law Smith, M J; Perrett, D I; Sharp, M A; Al-Dujaili, E A S

    2007-02-01

    Findings from previous studies of hormone-mediated behavior in women suggest that raised progesterone level increases the probability of behaviors that will reduce the likelihood of disruption to fetal development during pregnancy (e.g. increased avoidance of sources of contagion). Here, we tested women's (N=52) sensitivity to potential cues to nearby sources of contagion (disgusted facial expressions with averted gaze) and nearby physical threat (fearful facial expressions with averted gaze) at two points in the menstrual cycle differing in progesterone level. Women demonstrated a greater tendency to perceive fearful and disgusted expressions with averted gaze as more intense than those with direct gaze when their progesterone level was relatively high. By contrast, change in progesterone level was not associated with any change in perceptions of happy expressions with direct and averted gaze, indicating that our findings for disgusted and fearful expressions were not due to a general response bias. Collectively, our findings suggest women are more sensitive to facial cues signalling nearby contagion and physical threat when raised progesterone level prepares the body for pregnancy.

  12. Trial protocol OPPTIMUM– Does progesterone prophylaxis for the prevention of preterm labour improve outcome?

    Directory of Open Access Journals (Sweden)

    Norman Jane E

    2012-08-01

    Full Text Available Abstract Background Preterm birth is a global problem, with a prevalence of 8 to 12% depending on location. Several large trials and systematic reviews have shown progestogens to be effective in preventing or delaying preterm birth in selected high risk women with a singleton pregnancy (including those with a short cervix or previous preterm birth. Although an improvement in short term neonatal outcomes has been shown in some trials these have not consistently been confirmed in meta-analyses. Additionally data on longer term outcomes is limited to a single trial where no difference in outcomes was demonstrated at four years of age of the child, despite those in the “progesterone” group having a lower incidence of preterm birth. Methods/Design The OPPTIMUM study is a double blind randomized placebo controlled trial to determine whether progesterone prophylaxis to prevent preterm birth has long term neonatal or infant benefit. Specifically it will study whether, in women with singleton pregnancy and at high risk of preterm labour, prophylactic vaginal natural progesterone, 200 mg daily from 22 – 34 weeks gestation, compared to placebo, improves obstetric outcome by lengthening pregnancy thus reducing the incidence of preterm delivery (before 34 weeks, improves neonatal outcome by reducing a composite of death and major morbidity, and leads to improved childhood cognitive and neurosensory outcomes at two years of age. Recruitment began in 2009 and is scheduled to close in Spring 2013. As of May 2012, over 800 women had been randomized in 60 sites. Discussion OPPTIMUM will provide further evidence on the effectiveness of vaginal progesterone for prevention of preterm birth and improvement of neonatal outcomes in selected groups of women with singleton pregnancy at high risk of preterm birth. Additionally it will determine whether any reduction in the incidence of preterm birth is accompanied by improved childhood outcome. Trial

  13. Progesterone levels and days to luteolysis in mares treated with intrauterine fractionated coconut oil.

    Science.gov (United States)

    Diel de Amorim, Mariana; Nielsen, Kayla; Cruz, Raissa Karolliny Salgueiro; Card, Claire

    2016-07-15

    Intrauterine plant oil infusion, including fractionated coconut oil, has been previously found to be a safe, inexpensive, and reversible method of prolonging the luteal phase in mares when administered on Day 10 of the estrous cycle. Our objective was to understand the uteroovarian response to the administration of fractionated coconut oil infusion in the uterus of diestrous mares. We hypothesized that intrauterine coconut oil administration on Day 10 would prolong luteal life span in a dose-dependent fashion and would result in higher serum progesterone levels than untreated mares at the expected time of luteolysis. Light-horse mares (n = 18) were examined using transrectal palpation and ultrasonography to determine if they had a normal interovulatory interval and were then examined daily in estrus until the day of ovulation (Day 0) and then every other day during an estrous cycle. Jugular blood was drawn on Day 11, Day 13, Day 15, and Day 17, centrifuged, and serum stored until assayed for progesterone (P4; Siemens Coat-a-Count Progesterone RIA, Los Angeles, CA, USA). Mares were randomly assigned to treatment and studied over one to two estrous cycles with a rest cycle after each treatment cycle. Groups were: control (n = 5), fractionated coconut oil 1.0 mL (Miglyol 810; Sasol Oil, Witten, Germany) infused in the uterus with an artificial insemination pipette on Day 10 (Group 1; n = 5) and fractionated coconut oil 0.5 mL infused in the uterus with an embryo transfer gun, on Day 10 (Group 2; n = 5). All statistical analyses were performed using analytical software (Stata SE, version 13.1, College Station, TX, USA) at P coconut oil lowered P4 levels in diestrus in a dose-dependent fashion and did not prolonged the luteal phase of the mares. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Inhibin secretion in women with the polycystic ovary syndrome before and after treatment with progesterone

    Directory of Open Access Journals (Sweden)

    Anifandis George

    2011-04-01

    Full Text Available Abstract Objectives It has been suggested that inhibin secretion is altered in women with the polycystic ovary syndrome (PCOS. However, the contribution of a preceding luteal phase has not been taken into account. The aim of the present study was to investigate whether progesterone in the context of a simulated luteal phase affects basal and FSH-induced inhibin secretion in women with PCOS and elevated LH. Methods Ten women with PCOS and 8 normally cycling women participated in an experimental procedure (Exp involving the administration of a single injection of recombinant FSH (450 IU sc. In the women with PCOS, the procedure was performed before (Exp 1 and after a 20-day treatment with progesterone (Exp 2, while in the normal women on day 2 of the cycle (Exp 3. Inhibin A and B levels were measured in blood samples taken before and 24 hours after the FSH injection. Results Basal LH levels were significantly higher and inhibin A levels were significantly lower in the PCOS group compared to the control group, while inhibin B levels were comparable in the two groups. In the PCOS group, after treatment with progesterone inhibin A and LH but not inhibin B levels decreased significantly (p Conclusions In women with PCOS, as compared to control women, the dissimilar pattern of inhibin A and inhibin B secretion in response to FSH appears to be independent of a preceding simulated luteal phase. It is possible that compared to normal ovaries, the PCOS ovaries are less sensitive to endogenous LH regarding inhibin A secretion and more sensitive to exogenous FSH stimulation in terms of inhibin A and inhibin B secretion.

  15. The effect of intramuscular administration of medroxy progesterone acetate (MPA on electrocardiographic alterations of female dogs

    Directory of Open Access Journals (Sweden)

    M Neshat Gharamaleky

    2010-11-01

    Full Text Available Progestins are useful for hormonal prevention of pregnancy in humans and animals. Progestrone and medroxy progestrone acetate are used for treatment of premenopausal syndrome and decreasing complications of estrogen therapy after menopause. Prescription of progesterone in dogs is usually done to control or delay estrus. If this drug is used at anestrous it will inhibit the gonadotropin excretion beyond the basic level and it will prevent cycle from happening again in proestrus or at the beginning of estrus progesterone will prevent ovulation. Use of progesterone is not totally safe in bitches. It can cause several problems such as cystic endometrial hyperplasia and pyrometera. In this study the effects of medroxy progestrone acetat (MPA on electrocardiographic changes are evaluated. After nutritional and environmental uniformity and other evaluations, the animals were divided into two groups with six bitches in each group. MPA was used at 10 mg/kg for the first group and 20 mg/kg for the second group. An ECG was recorded from the first group in time zero. MPA was injected intramuscularly and immediately after ECG recording and the time of injection was noted. Another ECG was recorded 0.5 and 2 hours after injection. The same process was repeated for the second group. It was observed that MPA at 20 mg/kg increased the heart rate and consequently PR interval and RR interval were decreased significantly in normal range. Also administration of drug at 10 mg/kg decreased the heart rate and increased PR interval, QT interval and RR interval significantly in normal range. It is probable that these observations are the result of MPAs dose dependent vasodilatory nature that induces the heart to exhibit compensative reactions such as increasing heart rate.

  16. Sex and estrous cycle influence diazepam effects on anxiety and memory: Possible role of progesterone.

    Science.gov (United States)

    Silva, Anatildes Feitosa; Sousa, Diego Silveira; Medeiros, André Macêdo; Macêdo, Priscila Tavares; Leão, Anderson Henrique; Ribeiro, Alessandra Mussi; Izídio, Geison Souza; Silva, Regina Helena

    2016-10-03

    Studies with rodents and humans show the relationship between female sex hormones and cognitive/emotional tasks. However, despite the greater incidence of anxiety disorders in women, the data are still inconclusive regarding the mechanisms related to this phenomenon. We evaluated the effects of a classical anxiolytic/amnestic drug (diazepam; DZP) on female (at different estrous cycle phases) and male rats tested in the plus-maze discriminative avoidance task (PMDAT), that allows the concomitant evaluation of memory and anxiety-like behavior. Further, in order to investigate the role of progesterone and its metabolites in the effects of DZP in the PMDAT, female rats were pre-treated with the progesterone receptor antagonist mifepristone or the 5-alpha-reductase inhibitor finasteride. The main findings were: (1) DZP caused memory impairment and anxiolysis in both sexes, but only the highest dose induced the anxiolytic effect in females; (2) females in proestrus did not present the amnestic and anxiolytic effects of DZP (at 2.0 and 4.0mg/kg, respectively) and (3) the co-administration of mifepristone reestablished both amnestic and anxiolytic effects of DZP, while finasteride reinstated the amnestic effect in proestrus female rats. These results suggest that changes in the endogenous levels of progesterone and its metabolites are important in the modulation of emotional/cognitive behavior in female rats. Based on the influence on different aspects of DZP action, the mechanisms related to this modulation are probably linked to GABAergic transmission, but this point remains to be investigated. Further, the variation in therapeutic and adverse effects of DZP depending on sex and hormonal state is of great relevance considering the higher prevalence of anxiety disorders in women. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Progesterone mediates brain functional connectivity changes during the menstrual cycle - A pilot resting state MRI study

    Directory of Open Access Journals (Sweden)

    Katrin eArelin

    2015-02-01

    Full Text Available The growing interest in intrinsic brain organization has sparked various innovative approaches to generating comprehensive connectivity-based maps of the human brain. Prior reports point to a sexual dimorphism of the structural and functional human connectome. However, it is uncertain whether subtle changes in sex hormones, as occur during the monthly menstrual cycle, substantially impact the functional architecture of the female brain. Here, we performed eigenvector centrality (EC mapping in 32 longitudinal resting state fMRI scans of a single healthy subject without oral contraceptive use, across four menstrual cycles, and assessed estrogen and progesterone levels. To investigate associations between cycle-dependent hormones and brain connectivity, we performed correlation analyses between the EC maps and the respective hormone levels. On the whole brain level, we found a significant positive correlation between progesterone and EC in the bilateral DLPFC and bilateral sensorimotor cortex. In a secondary region-of-interest analysis, we detected a progesterone-modulated increase in functional connectivity of both bilateral DLPFC and bilateral sensorimotor cortex with the hippocampus. Our results suggest that the menstrual cycle substantially impacts intrinsic functional connectivity, particularly in brain areas associated with contextual memory-regulation, such as the hippocampus. These findings are the first to link the subtle hormonal fluctuations that occur during the menstrual cycle, to significant changes in regional functional connectivity in the hippocampus in a longitudinal design, given the limitation of data acquisition in a single subject. Our study demonstrates the feasibility of such a longitudinal rs-fMRI design and illustrates a means of creating a personalized map of the human brain by integrating potential mediators of brain states, such as menstrual cycle phase.

  18. Progesterone 5β-reductase genes of the Brassicaceae family as function-associated molecular markers.

    Science.gov (United States)

    Munkert, J; Costa, C; Budeanu, O; Petersen, J; Bertolucci, S; Fischer, G; Müller-Uri, F; Kreis, W

    2015-11-01

    This study aimed to define progesterone 5β-reductases (P5βR, EC 1.3.99.6, enone 1,4-reductases) as function-associated molecular markers at the plant family level. Therefore cDNAs were isolated from 25 Brassicaceae species, including two species, Erysimum crepidifolium and Draba aizoides, known to produce cardiac glycosides. The sequences were used in a molecular phylogeny study. The cladogram created is congruent to the existing molecular analyses. Recombinant His-tagged forms of the P5βR cDNAs from Aethionema grandiflorum, Draba aizoides, Nasturtium officinale, Raphanus sativus and Sisymbrium officinale were expressed in E. coli. Enone 1,4-reductase activity was demonstrated in vitro using progesterone and 2-cyclohexen-1-one as substrates. Evidence is provided that functional P5βRs are ubiquitous in the Brassicaceae. The recombinant P5βR enzymes showed different substrate preferences towards progesterone and 2-cyclohexen-1-one. Sequence comparison of the catalytic pocket of the P5βR enzymes and homology modelling using Digitalis lanata P5βR (PDB ID: 2V6G) as template highlighted the importance of the hydrophobicity of the binding pocket for substrate discrimination. It is concluded that P5βR genes or P5βR proteins can be used as valuable function-associated molecular markers to infer taxonomic relationship and evolutionary diversification from a metabolic/catalytic perspective. © 2015 German Botanical Society and The Royal Botanical Society of the Netherlands.

  19. Obesity Disrupts the Rhythmic Profiles of Maternal and Fetal Progesterone in Rat Pregnancy.

    Science.gov (United States)

    Crew, Rachael C; Mark, Peter J; Clarke, Michael W; Waddell, Brendan J

    2016-09-01

    Maternal obesity increases the risk of abnormal fetal growth, but the underlying mechanisms remain unclear. Because steroid hormones regulate fetal growth, and both pregnancy and obesity markedly alter circadian biology, we hypothesized that maternal obesity disrupts the normal rhythmic profiles of steroid hormones in rat pregnancy. Obesity was established by cafeteria (CAF) feeding for 8 wk prior to mating and throughout pregnancy. Control (CON) animals had ad libitum access to chow. Daily profiles of plasma corticosterone, 11-dehydrocorticosterone, progesterone, and testosterone were measured at Days 15 and 21 of gestation (term = 23 days) in maternal (both days) and fetal (Day 21) plasma. CAF mothers exhibited increased adiposity relative to CON and showed fetal and placental growth restriction. There was no change, however, in total fetal or placental mass due to slightly larger litter sizes in CAF. Nocturnal declines in progesterone were observed in maternal (39% lower) and fetal (45% lower) plasma in CON animals, but these were absent in CAF animals. CAF mothers were hyperlipidemic at both days of gestation, but this effect was isolated to the dark period at Day 21. CAF maternal testosterone was slightly lower at Day 15 (8%) but increased above CON by Day 21 (16%). Despite elevated maternal testosterone, male fetal testosterone was suppressed by obesity on Day 21. Neither maternal nor fetal glucocorticoid profiles were affected by obesity. In conclusion, obesity disrupts rhythmic profiles of maternal and fetal progesterone, preventing the normal nocturnal decline. Obesity subtly changed testosterone profiles but did not alter maternal and fetal glucocorticoids. © 2016 by the Society for the Study of Reproduction, Inc.

  20. Effect of the Novel Selective Progesterone Receptor Modulator Vilaprisan on Ovarian Activity in Healthy Women.

    Science.gov (United States)

    Schütt, Barbara; Schultze-Mosgau, Marcus-Hillert; Draeger, Corinna; Chang, Xinying; Löwen, Stephanie; Kaiser, Andreas; Rohde, Beate

    2017-09-21

    This randomized, double-blind, parallel-group study in healthy young women investigated the effect of treatment with vilaprisan (0.5, 1, 2, or 4 mg/day for 12 weeks) on ovarian function by assessing the Hoogland score, which is based on the size of follicle-like structures as determined by transvaginal ultrasound and on estradiol and progesterone serum concentrations. Ovulation inhibition (ie, Hoogland score 80% of the subjects receiving vilaprisan ≥1 mg/day. The effect was dose dependent. With a Bayesian approach, the percentage of subjects with ovulation inhibition was estimated to increase from 37% in subjects receiving 0.5 mg/day vilaprisan to 76%, 86%, and 88% in subjects receiving 1, 2, and 4 mg/day, respectively. Follicle growth was not suppressed during treatment. The majority of subjects receiving ≥1 mg/day had a Hoogland score of 4 (active follicle-like structures, ie, follicle diameter >13 mm, estradiol >27.2 pg/mL, no progesterone increase) both at beginning and end of treatment. Mean average estradiol as well as mean maximum progesterone concentrations were noticeably decreased during treatment with vilaprisan ≥1 mg/day compared to pretreatment, but estradiol concentrations remained >80 pg/mL. Both hormones returned to pretreatment levels after the end of treatment, indicating a rapid resumption of normal ovarian activity. Amenorrhea occurred in the majority of subjects during treatment at dosages ≥1 mg/day. The adverse events observed in this study confirm the known safety profile of vilaprisan. All in all, the results of this study support the development of vilaprisan for the long-term treatment of uterine fibroids. © 2017, The Authors. The Journal of Clinical Pharmacology Published by Wiley Periodicals, Inc. on behalf of American College of Clinical Pharmacology.

  1. /sup 125/I-progesterone radioimmunoassay for fertility control in cows

    Energy Technology Data Exchange (ETDEWEB)

    Herzmann, H.; Herzmann, A.; Flentje, H.; Schmidt, H.E. (Akademie der Wissenschaften der DDR, Berlin-Buch. Zentralinstitut fuer Isotopen- und Strahlenforschung); Barth, T.; Hempel, G.; Graeser, K. (Bezirksinstitut fuer Veterinaerwesen Dresden (German Democratic Republic))

    1985-09-01

    A /sup 125/I RIA has been developed for progesterone determination in full-cream milk, skimmed milk and blood plasma. Because of its specificity, accuracy and practicability it is particularly suitable for routine work. First experience has been gained in field studies on fertility control of cows. As early as one estrous cycle after insemination, non-pregnant cows can be distinguished from presumably pregnant ones with a high degree of certainty, so that a timely re-insemination of those animals is rendered possible. Insemination outside the estrous cycle was found to be one reason for supposed fertility disorders.

  2. Activation of the kinin system in the ovary during ovulation: Role of endogenous progesterone

    Directory of Open Access Journals (Sweden)

    Mahesh Virendra B

    2002-04-01

    Full Text Available Abstract Background Previous work by our group and others has implicated a role for kinins in the ovulatory process. The purpose of the present study was to elucidate whether endogenous progesterone, which is an intraovarian regulator of ovulation, might be responsible for induction of the kinin system in the ovary during ovulation. The gonadotropin-primed immature rat was used as the experimental model, and the role of endogenous progesterone was explored using the antiprogestin, RU486. Results The results of the study revealed that RU486 treatment, as expected, significantly attenuated ovulation. Activity of the kinin-generating enzyme, kallikrein, was elevated in the ovary in control animals prior to ovulation with peak values observed at 4 h post hCG, only to fall to low levels at 10 h, with a recovery at 20 h post hCG. RU486 treatment had no significant effect on ovarian kallikrein activity as compared to the control group. Total ovarian kininogen levels in control animals increased significantly at 12–14 h after hCG – coinciding with initiation of ovulation. Thereafter, ovarian kininogen levels fell to low levels at 20 h, only to show a rebound from 24–38 h post-hCG. RU486 treatment had no significant effect on the rise of total ovarian kininogen levels from 12–14 h after hCG; however, from 30–40 h post hCG, RU486-treated animals had significantly higher total ovarian kininogen levels versus control animals, suggesting that endogenous progesterone may act to restrain elevations of kininogens in the post-ovulatory ovary. This robust elevation of ovarian kininogen levels by RU486 was found to be primarily due to an increase in T-kininogen, which is a potent cysteine protease inhibitor. Conclusions Taken as a whole, these results suggest that endogenous progesterone does not regulate kallikrein activity or kininogens prior to ovulation, but may provide a restraining effect on T-kininogen levels in the post-ovulatory ovary.

  3. Neurotox-98 Neuroprotection by Progesterones Through Stimulation of Mitochondrial Gene Expression

    Science.gov (United States)

    2006-06-01

    progesterone, and DBI. Biol. Psychiat. 35, 775–780. Gillardon, F., Wickert, H., Zimmermann , M., 1995. Up-regulation of bax and down-regulation of bcl-2 is...Protection Against Ischemic Brain Injury by Inhibition of Mitochondrial Oxidative Stress Gary Fiskum,1,2,6 Robert E. Rosenthal,1,2 Viktoria Vereczki,1 Erica...Cortical Impact Reduces Peroxynitrite-Mediated Protein Nitration in the Hippocampus Edward S. Ahn, M.D., Courtney L. Robertson, M.D., Viktoria Vereczki, M.D

  4. Genetics of Fertility Indicators Based on Behaviour and Progesterone in Milk

    DEFF Research Database (Denmark)

    Løvendahl, P; Chagunda, M; O'Connell, J

    2009-01-01

    Genetic selection for female is diffecult because current records based on AI information are biased from farmer's decisions and have low heritablity (h2 = 0.03). Automated on-farm progesterone based heat detection methods are becoming commercially available, as has eqipment based on behaviour...... monitoring using activity meters already been for some time. Data from a research herd show that the heritablility of days to first oestrus is between 0.21 and 0.27 using these types of equipments. Collection of data from both types of automated equipment would offer unbiased informationon days to first...

  5. [Estrogen and progesterone receptors in non carcinomatous breast diseases (author's transl)].

    Science.gov (United States)

    May-Levin, F; Contesso, G; Guerinot, F; Delarue, J C; Bohuon, C

    1977-04-01

    Cytosolic receptors for estrogens and progesterone are studied using an exchange method in various types of benign breast diseases: fibroadenomas, fibrocystic mastosis, phylloid tumors and gynecomastias. The results show clearly that, contrary to breast carcinomas, receptors are generally not present in benign tumors. These results are statistically significant for all the women studied. Studying the pathological aspects of the tumors, it can be noted that the presence of receptors, is correlated with proliferation forms with large epithelial components. Furthermore, these results show that receptors are not found in gynecomastia. In conclusion, the physician should follow up very carefully the patients with a benign tumor, when hormono-receptors are present.

  6. Roles of estrogen and progesterone in modulating renal nerve function in the rat kidney

    Energy Technology Data Exchange (ETDEWEB)

    Graceli, J.B. [Departamento de Morfologia, Centro de Ciências da Saúde, Universidade Federal do Espírito Santo, Vitória, ES (Brazil); Cicilini, M.A.; Bissoli, N.S.; Abreu, G.R.; Moysés, M.R. [Departamento de Ciências Fisiológicas, Centro de Ciências da Saúde, Universidade Federal do Espírito Santo, Vitória, ES (Brazil)

    2013-07-02

    The maintenance of extracellular Na{sup +} and Cl{sup -} concentrations in mammals depends, at least in part, on renal function. It has been shown that neural and endocrine mechanisms regulate extracellular fluid volume and transport of electrolytes along nephrons. Studies of sex hormones and renal nerves suggested that sex hormones modulate renal function, although this relationship is not well understood in the kidney. To better understand the role of these hormones on the effects that renal nerves have on Na{sup +} and Cl{sup -} reabsorption, we studied the effects of renal denervation and oophorectomy in female rats. Oophorectomized (OVX) rats received 17β-estradiol benzoate (OVE, 2.0 mg·kg{sup -1}·day{sup -1}, sc) and progesterone (OVP, 1.7 mg·kg{sup -1}·day{sup -1}, sc). We assessed Na{sup +} and Cl{sup -} fractional excretion (FE{sub Na{sup {sub +}}} and FE{sub Cl{sup {sub -}}}, respectively) and renal and plasma catecholamine release concentrations. FE{sub Na{sup {sub +}}}, FE{sub Cl{sup {sub -}}}, water intake, urinary flow, and renal and plasma catecholamine release levels increased in OVX vs control rats. These effects were reversed by 17β-estradiol benzoate but not by progesterone. Renal denervation did not alter FE{sub Na{sup {sub +}}}, FE{sub Cl{sup {sub -}}}, water intake, or urinary flow values vs controls. However, the renal catecholamine release level was decreased in the OVP (236.6±36.1 ng/g) and denervated rat groups (D: 102.1±15.7; ODE: 108.7±23.2; ODP: 101.1±22.1 ng/g). Furthermore, combining OVX + D (OD: 111.9±25.4) decreased renal catecholamine release levels compared to either treatment alone. OVE normalized and OVP reduced renal catecholamine release levels, and the effects on plasma catecholamine release levels were reversed by ODE and ODP replacement in OD. These data suggest that progesterone may influence catecholamine release levels by renal innervation and that there are complex interactions among renal nerves, estrogen

  7. [Profiles of estrone, estrone sulfate and progesterone in donkey (Equus asinus) mares during pregnancy].

    Science.gov (United States)

    Hoffmann, B; Bernhardt, A W; Failing, K; Schuler, G

    2014-01-01

    To gain further data on the hormonal control of pregnancy in the donkey and to obtain reference values for hormonal pregnancy testing. Blood samples were collected at monthly intervals from 23 donkey mares with normal singleton pregnancies. Further samples were obtained from six mares displaying pregnancies with clinical disorders. Progesterone (P4), total estrone (TE), free (E) and conjugated estrone (ES) were determined using radioimmunoassay. Mean duration of pregnancy was 372 ± 16 days. It was longer (p 5 ng/ml being indicative for pregnancy. At present, monitoring of P4 and estrone during pregnancy does not allow the prediction of clinical disorders.

  8. The influence of progesterone alone and in combination with estradiol on ventricular action potential duration and triangulation in response to potassium channel inhibition.

    Science.gov (United States)

    Tisdale, James E; Overholser, Brian R; Wroblewski, Heather A; Sowinski, Kevin M

    2011-03-01

    Females are at increased risk for torsades de pointes (TdP). Some evidence suggests that progesterone may protect against TdP, but few data exist regarding the effects of progesterone on cardiac repolarization. We determined the effects of progesterone alone and in combination with estradiol on ventricular action potential duration (APD) and triangulation in response to potassium channel inhibition. Female New Zealand white rabbits (n = 30) underwent ovariectomy and were implanted with 21-day sustained release pellets (each n = 6): progesterone; estradiol; progesterone; & estradiol combined; dihydrotestosterone (DHT); and placebo. After 20 days, hearts were excised, mounted, perfused with modified Krebs-Henseleit buffer, and paced at 150 bpm. After baseline measurements, hearts were perfused with quinidine 3 μmol/L. The degree of quinidine-associated prolongation of ventricular APD at 90% repolarization (APD(90) ) in the progesterone group was significantly less than that in the estradiol and the combined estradiol and progesterone groups, and not significantly different than in the DHT group. The degree of prolongation of action potential triangulation (APD(90) - APD(30) ) in hearts from progesterone-treated rabbits was significantly less than that in the estradiol group, and not significantly different from that in hearts from DHT-treated rabbits. There were no significant differences in quinidine effects on ventricular APD(90) or action potential triangulation between hearts exposed to estradiol alone or those exposed to both estradiol and progesterone. Progesterone protects against prolongation of APD(90) and triangulation associated with potassium channel inhibition. However, progesterone does not attenuate the effects of estradiol on prolongation of ventricular APD(90) associated with potassium channel inhibition. © 2010 Wiley Periodicals, Inc.

  9. Mammary tumors and serum hormones in the bitch treated with medroxyprogesterone acetate or progesterone for four years

    Energy Technology Data Exchange (ETDEWEB)

    Frank, D.W.; Kirton, K.T.; Murchison, T.E.; Quinlan, W.J.; Coleman, M.E.; Gilbertson, T.J.; Feenstra, E.S.; Kimball, F.A.

    1978-01-01

    After four years of a long term contraceptive steroid safety study, the incidence and the histologic type of mammary dysplasia produced is similar in beagles treated with medroxyprogesterone acetate (medroxyprogesterone) or progesterone. Serum insulin, thyroid stimulating hormone (TSH), triiodothyronine, growth hormone, prolactin, 17..beta..-estradiol, progesterone, and cortisol were determined by radioimmunoassay on samples collected after 45 months of treatment. Serum growth hormone and insulin concentrations were elevated in a dose related manner in both treatment groups. Triiodothyronine, cortisol, and estradiol-17..beta.. (medroxyprogesterone only) were lowered. TSH and prolactin concentrations were not changed. Pituitary--gonadal hormone interaction in the pathogenesis of mammary neoplasia of the dog is discussed. Prolonged treatment of the beagle with massive doses of progesterone or medroxyprogesterone results in a dose related incidence of mammary modules.

  10. Solvent effects on infrared spectra of progesterone in CHCl3/cyclo-C6H12 binary solvent systems.

    Science.gov (United States)

    Liu, Qing; Wang, Xiao-Yan; Zhang, Hui

    2007-01-01

    The infrared spectroscopy studies of the C3 and C20 carbonyl stretching vibrations (upsilon(C=O)) of progesterone in CHCl3/cyclo-C6H12 binary solvent systems were undertaken to investigate the solute-solvent interactions. With the mole fraction of CHC13 in the binary solvent mixtures increase, three types of C3 and C20 carbonyl stretching vibration band of progesterone are observed, respectively. The assignments of upsilon(C=O) of progesterone are discussed in detail. In the CHCl3-rich binary solvent systems or pure CHCl3 solvent, two kinds of solute-solvent hydrogen bonding interactions coexist for C20 C=O. Comparisons are drawn for the solvent sensitivities of upsilon(C=O) for acetophenone and 5alpha-androstan-3,17-dione, respectively.

  11. Progesterone Alleviates Endometriosis via Inhibition of Uterine Cell Proliferation, Inflammation and Angiogenesis in an Immunocompetent Mouse Model.

    Directory of Open Access Journals (Sweden)

    Yanfen Li

    Full Text Available Endometriosis, defined as growth of the endometrial cells outside the uterus, is an inflammatory disorder that is associated with chronic pelvic pain and infertility in women of childbearing age. Although the estrogen-dependence of endometriosis is well known, the role of progesterone in development of this disease remains poorly understood. In this study, we developed a disease model in which endometriosis was induced in the peritoneal cavities of immunocompetent female mice, and maintained with exogenous estrogen. The endometriosis-like lesions that were identified at a variety of ectopic locations exhibited abundant blood supply and extensive adhesions. Histological examination revealed that these lesions had a well-organized endometrial architecture and fibrotic response, resembling those recovered from clinical patients. In addition, an extensive proliferation, inflammatory response, and loss of estrogen receptor alpha (ERα and progesterone receptor (PR expression were also observed in these lesions. Interestingly, administration of progesterone before, but not after, lesion induction suppressed lesion expansion and maintained ERα and PR expressions. These progesterone-pretreated lesions exhibited attenuation in KI67, CD31, and pro-inflammatory cytokine expression as well as macrophage infiltration, indicating that progesterone ameliorates endometriosis progression by inhibiting cell proliferation, inflammation and neovascularization. Our studies further showed that suppression of global DNA methylation by application of DNA methyltransferase inhibitor to female mice bearing ectopic lesions restrained lesion expansion and restored ERα and PR expression in eutopic endometrium and ectopic lesions. These results indicate that epigenetic regulation of target gene expression via DNA methylation contributes, at least in part, to progesterone resistance in endometriosis.

  12. Progesterone impairs antigen-non-specific immune protection by CD8 T memory cells via interferon-γ gene hypermethylation.

    Directory of Open Access Journals (Sweden)

    Yushi Yao

    2017-11-01

    Full Text Available Pregnant women and animals have increased susceptibility to a variety of intracellular pathogens including Listeria monocytogenes (LM, which has been associated with significantly increased level of sex hormones such as progesterone. CD8 T memory(Tm cell-mediated antigen-non-specific IFN-γ responses are critically required in the host defense against LM. However, whether and how increased progesterone during pregnancy modulates CD8 Tm cell-mediated antigen-non-specific IFN-γ production and immune protection against LM remain poorly understood. Here we show in pregnant women that increased serum progesterone levels are associated with DNA hypermethylation of IFN-γ gene promoter region and decreased IFN-γ production in CD8 Tm cells upon antigen-non-specific stimulation ex vivo. Moreover, IFN-γ gene hypermethylation and significantly reduced IFN-γ production post LM infection in antigen-non-specific CD8 Tm cells are also observed in pregnant mice or progesterone treated non-pregnant female mice, which is a reversible phenotype following demethylation treatment. Importantly, antigen-non-specific CD8 Tm cells from progesterone treated mice have impaired anti-LM protection when adoptive transferred in either pregnant wild type mice or IFN-γ-deficient mice, and demethylation treatment rescues the adoptive protection of such CD8 Tm cells. These data demonstrate that increased progesterone impairs immune protective functions of antigen-non-specific CD8 Tm cells via inducing IFN-γ gene hypermethylation. Our findings thus provide insights into a new mechanism through which increased female sex hormone regulate CD8 Tm cell functions during pregnancy.

  13. Luteolytic efficiency of reduced doses of cloprostenol in the ewe. Effect of progesterone concentrations at the time of treatment.

    Science.gov (United States)

    Granados-Villarreal, Luz María; Zarco, Luis; Mejía, Octavio; Sánchez-Torres, María Teresa; Pablos-Hach, José Luis

    2017-11-01

    Seventy six ewes were treated with 7.5, 12.5, 25 or 50μg of cloprostenol on day 6 or 9 post-estrus to compare the luteolytic efficiency of the PGF2α analogue at each stage and to evaluate if progesterone concentrations at the time of treatment affect such efficiency. Blood samples were obtained before cloprostenol administration and 12, 24, 48, and 72h thereafter. There was an effect of dose (p<0.05) but not of day post-estrus on the proportion of animals completing luteolysis. As the dose increased, the proportion of ewes completing luteolysis also increased. Also, as the dose increased from 7.5 to 25μg, more ewes showed a transient progesterone decline instead of an absence of response, indicating that in some ewes reduced doses initiated luteolysis but were not able to finish the process. Since the dose of 25μg resulted in close to 50% luteolytic efficacy, this group was used to study the effects of progesterone concentrations at the time of treatment on the response to cloprostenol. Pre-treatment progesterone concentrations were higher (p<0.01) in ewes experiencing luteolytic failure than in those that completed luteolysis. There was a negative correlation between initial progesterone concentrations and their reduction by 12h post-treatment. It is concluded that high progesterone concentrations are associated with a reduction in sensitivity to small doses of cloprostenol. Possible mechanisms and implications of this luteoprotective effect are discussed. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Regulation of UDP-glucuronosyltransferase (UGT) 1A1 by progesterone and its impact on labetalol elimination.

    Science.gov (United States)

    Jeong, H; Choi, S; Song, J W; Chen, H; Fischer, J H

    2008-01-01

    The authors recently reported the increased oral clearance of labetalol in pregnant women. To elucidate the mechanism of the elevated oral clearance, it was hypothesized that female hormones, at the high concentrations attainable during pregnancy, enhance hepatic metabolism of labetalol. Labetalol glucuronidation, which is the major elimination pathway of labetalol, was characterized by screening six recombinant human UGTs (UGT1A1, 1A4, 1A6, 1A9, 2B4, and 2B7) for their capacity to catalyse labetalol glucuronidation. The effect of female hormones (progesterone, oestradiol, oestriol, or oestrone) on the promoter activities of relevant UDP glucuronosyltransferases (UGT) was investigated using a luciferase reporter assay in HepG2 cells. The involvement of oestrogen receptor alpha (ERalpha) and pregnane X receptor (PXR) was examined by co-transfecting ERalpha- or PXR-constructs. UGT1A1 and UGT2B7 were identified as the major UGT enzymes producing labetalol glucuronides (trace amount of glucuronide conjugate was formed by UGT1A9). The activities of the UGT1A1 promoter containing PXR response elements were enhanced by progesterone, but not by oestrogens, indicating PXR-mediated induction of UGT1A1 promoter activity by progesterone. Results from semi-quantitative real-time polymerase chain reaction (PCR) assays are consistent with the above findings. This effect of progesterone on UGT1A1 promoter activities was concentration dependent. Promoter activities of UGT2B7 were not affected by either oestrogens or progesterone. The results suggest a potential role for progesterone in regulating labetalol elimination by modulating the expression of UGT1A1, leading to enhanced drug metabolism during pregnancy.

  15. Extra-nuclear signaling of progesterone receptor to breast cancer cell movement and invasion through the actin cytoskeleton.

    Directory of Open Access Journals (Sweden)

    Xiao-Dong Fu

    2008-07-01

    Full Text Available Progesterone plays a role in breast cancer development and progression but the effects on breast cancer cell movement or invasion have not been fully explored. In this study, we investigate the actions of natural progesterone and of the synthetic progestin medroxyprogesterone acetate (MPA on actin cytoskeleton remodeling and on breast cancer cell movement and invasion. In particular, we characterize the nongenomic signaling cascades implicated in these actions. T47-D breast cancer cells display enhanced horizontal migration and invasion of three-dimensional matrices in the presence of both progestins. Exposure to the hormones triggers a rapid remodeling of the actin cytoskeleton and the formation of membrane ruffles required for cell movement, which are dependent on the rapid phosphorylation of the actin-regulatory protein moesin. The extra-cellular small GTPase RhoA/Rho-associated kinase (ROCK-2 cascade plays central role in progesterone- and MPA-induced moesin activation, cell migration and invasion. In the presence of progesterone, progesterone receptor A (PRA interacts with the G protein G alpha(13, while MPA drives PR to interact with tyrosine kinase c-Src and to activate phosphatidylinositol-3 kinase, leading to the activation of RhoA/ROCK-2. In conclusion, our findings manifest that progesterone and MPA promote breast cancer cell movement via rapid actin cytoskeleton remodeling, which are mediated by moesin activation. These events are triggered by RhoA/ROCK-2 cascade through partially differing pathways by the two compounds. These results provide original mechanistic explanations for the effects of progestins on breast cancer progression and highlight potential targets to treat endocrine-sensitive breast cancers.

  16. STOPPIT Baby Follow-up Study: the effect of prophylactic progesterone in twin pregnancy on childhood outcome.

    Directory of Open Access Journals (Sweden)

    Helen Christine McNamara

    Full Text Available To determine the long-term effects of in utero progesterone exposure in twin children.This study evaluated the health and developmental outcomes of all surviving children born to mothers who participated in a double-blind, placebo-controlled trial of progesterone given for the prevention of preterm birth in twin pregnancies (STOPPIT, ISRCTN35782581. Follow-up was performed via record linkage and two parent-completed validated questionnaires, the Child Development Inventory and the Health Utilities Index.Record linkage was successfully performed on at least one record in 759/781 (97% children eligible for follow-up. There were no differences between progesterone-exposed and placebo-exposed twins with respect to incidence of death, congenital anomalies and hospitalisation, nor on routine national child health assessments. Questionnaire responses were received for 324/738 (44% children. The mean age at questionnaire follow-up was 55.5 months. Delay in at least one developmental domain on the Child Development Inventory was observed in 107/324 (33% children, with no evidence of difference between progesterone-exposed and placebo-exposed twins. There was no evidence of difference between the progesterone and placebo groups in global health status assessed using the Health Utilities Index: 89% of children were rated as having 'excellent' health and a further 8% as having 'very good' health.In this cohort of twin children there was no evidence of a detrimental or beneficial impact on health and developmental outcomes at three to six years of age due to in utero exposure to progesterone.

  17. Progesterone Test

    Science.gov (United States)

    ... ovulation When symptoms, such as abdominal pain and spotting, suggest an ectopic pregnancy or threatened miscarriage On ... Partner | Advertise | License Sponsors and Partners Spread the Word Subscribe Awards Program of: © 2001-2018 by Lab ...

  18. Serum progesterone

    Science.gov (United States)

    ... Principles and Practice . 7th ed. Philadelphia, PA: Elsevier Saunders; 2014:chap 44. Review Date 5/9/2015 Updated by: Cynthia D. White, MD, Fellow American College of Obstetricians and Gynecologists, ...

  19. Progesterone Test

    Science.gov (United States)

    ... Urine Culture Urine Metanephrines Urine Protein and Urine Protein to Creatinine Ratio Valproic Acid Vancomycin Vanillylmandelic Acid (VMA) VAP Vitamin A Vitamin B12 and Folate Vitamin D Tests Vitamin K VLDL Cholesterol von Willebrand Factor Warfarin Sensitivity Testing ...

  20. ANTIBODIES TO BENZO[A]PYRENE, ESTRADIOL AND PROGESTERONE IN THE POSTMENOPAUSAL BREAST CANCER WOMEN

    Directory of Open Access Journals (Sweden)

    A. N. Glushkov

    2016-01-01

    Full Text Available The identification of women who are at high risk of developing breast cancer plays a key role in chemoprevention of breast cancer selective estrogen receptor modulators. purpose: To study specific immune responses to chemical carcinogens and sex steroid hormones associated with breast cancer in postmenopausal women. material and methods. Serum IgA-antibodies specific to benzo[a]pyrene, estradiol and progesterone were studied in 203 non-smoking healthy women and 469 non-smoking breast cancer patients (125 with ER– and 344 with ER+ using semi-quantitative enzyme immunoassay. results. The low levels of all three antibodies were revealed in 53.2 % of healthy donors, in 47.2 % of breast cancer patients with ER– and in 40.7 % of patients with ER+. The high levels of all three antibodies were found in 12.3 %, 18.4 % and 26.5 % of cases, respectively. In the studied groups, the levels of antibodies to estradiol and progesterone were correlated with the levels of antibodies to benzo[a]pyrene (rs=0.54–0.7, p<0.0001. Conclusion. Immunoassay of antibodies to exogenous and endogenous antigens could be useful for determining risk of developing ER+ breast cancer and preventing administration of tamoxifen and others selective modulators of estrogen receptors. Active immunization against exogenous chemical carcinogens could increase the levels of antibodies to endogenous steroids, thus stimulating breast cancer.

  1. Progesterone receptor gene (PROGINS) polymorphism correlates with late onset of migraine.

    Science.gov (United States)

    Palmirotta, Raffaele; Barbanti, Piero; Ialongo, Cristiano; De Marchis, Maria Laura; Alessandroni, Jhessica; Egeo, Gabriella; Aurilia, Cinzia; Fofi, Luisa; Valente, Maria Giovanna; Ferroni, Patrizia; Della-Morte, David; Guadagni, Fiorella

    2015-03-01

    Progesterone influences central neuronal excitability, a key event in migraine pathophysiology. Progesterone receptor gene (PGR) rs1042838 (G/T - Val660Leu) variant is indicative of PROGINS haplotype and associated to a reduced PGR activity. With the aim of investigating whether any type of association existed between this genetic variant and migraine pathophysiology, genotyping was performed in 380 consecutive migraine patients and 185 age-, sex-, and race-ethnicity-matched healthy controls from Interinstitutional Multidisciplinary BioBank (BioBIM) of IRCCS San Raffaele Pisana, Rome, Italy. rs1042838 genotypes did not correlate with demographics or clinical migraine features. However, TT (Leu) genotype was significantly associated with a later age of migraine onset: Patients affected by migraine with aura showed a linear relationship between copy number of the T allele carried by the individual and the age of migraine onset. Our data suggest that the PROGINS PGR polymorphism does not directly predispose to migraine but significantly delays migraine onset probably via a reduction in brain neuronal excitability.

  2. Laser Printing of PCL/Progesterone Tablets for Drug Delivery Applications in Hormone Cancer Therapy

    Science.gov (United States)

    Salmoria, G. V.; Klauss, P.; Kanis, L. A.

    2017-09-01

    In this study, polycaprolactone (PCL) and progesterone (PG) tablets were produced by selective laser sintering (SLS) using different particle sizes and laser energy. The sintered PCL/PG tablets presented uniform morphology, coalescence of particles and interconnected pores distributed in the polymeric matrix. The EDS analysis confirmed the presence of progesterone recrystallized on the surface of the porous PCL matrix. The crystallinity values for the PCL/PG tablets were lower than that for the pure PCL, suggesting the interaction of components at the molecular level. The PCL/PG tablets fabricated with small particles and high laser energy presented a higher value for the flexural modulus compared with the other specimens. The glass transition temperature (Tg) was -37 °C for the PCL/PG tablet with a high degree of sintering. The fatigue test showed that the PCL/PG blend tablets have high fatigue strength. The drug release mechanism of all tablets studied followed a zero-order kinetics, and drug release rates were dependent on sintering degree and, consequently, on matrix erosion, showing a potential application to controlled drug delivery in hormone cancer therapy.

  3. Distinct functions and regulation of epithelial progesterone receptor in the mouse cervix, vagina, and uterus.

    Science.gov (United States)

    Mehta, Fabiola F; Son, Jieun; Hewitt, Sylvia C; Jang, Eunjung; Lydon, John P; Korach, Kenneth S; Chung, Sang-Hyuk

    2016-04-05

    While the function of progesterone receptor (PR) has been studied in the mouse vagina and uterus, its regulation and function in the cervix has not been described. We selectively deleted epithelial PR in the female reproductive tracts using the Cre/LoxP recombination system. We found that epithelial PR was required for induction of apoptosis and suppression of cell proliferation by progesterone (P4) in the cervical and vaginal epithelium. We also found that epithelial PR was dispensable for P4 to suppress apoptosis and proliferation in the uterine epithelium. PR is encoded by the Pgr gene, which is regulated by estrogen receptor α (ERα) in the female reproductive tracts. Using knock-in mouse models expressing ERα mutants, we determined that the DNA-binding domain (DBD) and AF2 domain of ERα were required for upregulation of Pgr in the cervix and vagina as well as the uterine stroma. The ERα AF1 domain was required for upregulation of Pgr in the vaginal stroma and epithelium and cervical epithelium, but not in the uterine and cervical stroma. ERα DBD, AF1, and AF2 were required for suppression of Pgr in the uterine epithelium, which was mediated by stromal ERα. Epithelial ERα was responsible for upregulation of epithelial Pgr in the cervix and vagina. Our results indicate that regulation and functions of epithelial PR are different in the cervix, vagina, and uterus.

  4. Estrous cycle and stress: influence of progesterone on the female brain

    Directory of Open Access Journals (Sweden)

    T.A. Lovick

    2012-04-01

    Full Text Available The female brain operates in a constantly changing chemical milieu caused by cyclical changes in gonadal hormones during the estrous cycle (menstrual cycle in women. Such hormones are highly lipophilic and pass readily from the plasma to the brain where they can influence neuronal function. It is becoming clear that the rapid reduction in peripheral circulating progesterone, which occurs during the late diestrous phase of the cycle, can trigger a withdrawal-like response, in which changes in GABA A receptor expression render hyper-responsive certain brain areas involved in processing responses to stressful stimuli. The periaqueductal gray matter (PAG is recognised as an important region for integrating anxiety/defence responses. Withdrawal from progesterone, via actions of its neuroactive metabolite allopregnanolone, triggers up-regulation of extrasynaptic GABA A receptors on GABAergic neurons in the PAG. As a consequence, ongoing GABAergic tone on the output cells decreases, leading to an increase in functional excitability of the circuitry and enhanced responsiveness to stressful stimuli during the late diestrous phase. These changes during late diestrus could be prevented by short-term neurosteroid administration, timed to produce a more gradual fall in the peripheral concentration of allopregnanolone than the rapid decrease that occurs naturally, thus removing the trigger for the central withdrawal response.

  5. Efficient Prediction of Progesterone Receptor Interactome Using a Support Vector Machine Model

    Directory of Open Access Journals (Sweden)

    Ji-Long Liu

    2015-03-01

    Full Text Available Protein-protein interaction (PPI is essential for almost all cellular processes and identification of PPI is a crucial task for biomedical researchers. So far, most computational studies of PPI are intended for pair-wise prediction. Theoretically, predicting protein partners for a single protein is likely a simpler problem. Given enough data for a particular protein, the results can be more accurate than general PPI predictors. In the present study, we assessed the potential of using the support vector machine (SVM model with selected features centered on a particular protein for PPI prediction. As a proof-of-concept study, we applied this method to identify the interactome of progesterone receptor (PR, a protein which is essential for coordinating female reproduction in mammals by mediating the actions of ovarian progesterone. We achieved an accuracy of 91.9%, sensitivity of 92.8% and specificity of 91.2%. Our method is generally applicable to any other proteins and therefore may be of help in guiding biomedical experiments.

  6. Role of female sex hormones, estradiol and progesterone, in mast cell behaviour

    Directory of Open Access Journals (Sweden)

    Oliver eZierau

    2012-06-01

    Full Text Available Female sex hormones have long been suspected to have an effect on mast cell (MC behaviour. This assumption is based on the expression of hormone receptors in MCs as well as on the fact that many MC-related pathophysiological alterations have a different prevalence in females than in males. Further, serum IgE levels are much higher in allergic female mice compared to male mice. Ovariectomized rats developed less airway inflammation compared to sham controls. Following estrogen replacement ovariectomized rats re-established airway inflammation levels’ found in intact females. In humans, a much higher asthma prevalence was found in women at reproductive age as compared to men. Serum levels of estradiol and progesterone have been directly correlated with the clinical and functional features of asthma. Around 30 to 40% of women who have asthma experienced worsening of their symptoms during the perimenstrual phase, the so-called perimenstrual asthma. Postmenopausal women receiving hormone replacement therapy have an increased risk of new onset of asthma. Beside, estrus cycle dependent changes on female sex hormones are related to changes on MC number in mouse uterine tissue and estradiol and progesterone were shown to induce uterine MC maturation and degranulation. We will discuss here the currently available information concerning the role of these female sex hormones on MC behavior.

  7. Autoimmune Progesterone Dermatitis: A Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Fatma Çetinözman Aksoy

    2009-09-01

    Full Text Available Autoimmune progesteron dermatitis (AIPD is a rare disorder which is characterized by cyclical premenstrual flares of cutaneous or mucocutaneous manifestations. We present a 36-year-old woman with a 2-year history of oral ulcers and a rash which presents a week before every menstruation. She also had a history of recurrent herpes labialis infection; however herpes simplex virus could not be detected by PCR in oral lesions. Routine laboratory investigations, as well as serum complement levels were normal, except for elevated ANA titer (1/160. Histopathological examination of one of the papules was consistent with erythema multiforme and immunobullous diseases were ruled out by negative immunofluorescence studies. Based on the history and the clinical features, AIPD was suspected and the diagnosis was confirmed by flare of the lesions after progesterone challenge test. Subsequently, oral tamoxifen was started which controlled her flares significantly and no major side effects except amenorrhea was observed during treatment. Next she was given spironolactone which did not control her symptoms, therefore oral prednisolone had to be introduced. Due to its rare occurence, clinical features, pathogenesis, diagnostic and treatment alternatives of AIPD are discussed in this study based on the review of the medical literature.

  8. Comparison of neonatal outcomes following progesterone use during ovarian stimulation with frozen-thawed embryo transfer.

    Science.gov (United States)

    Zhu, Xiuxian; Ye, Hongjuan; Fu, Yonglun

    2017-08-10

    Progesterone soft capsules (brand name: Utrogestan) were demonstrated to be an effective oral alternative to prevent premature LH surges both in normal-ovulatory and polycystic ovarian syndrome (PCOS) patients. However, its safety in terms of neonatal outcomes is unclear. To evaluate whether Utrogestan use increase the risk of adverse neonatal outcomes compared with short protocol in patients undergoing IVF/ICSI treatments in combination with frozen-thawed embryo transfer (FET), we performed a retrospective analysis including 1008 FET cycles, with embryos originated from either Utrogestan + hMG protocol (n = 499), or short protocol (n = 509), which led to 546 live-born infants. The neonatal characteristics regarding preterm birth (PTB), low birth weight (LBW), gestational age and mode of delivery were comparable in the two groups. The incidence of live-birth defect was 0.68% (2/293) in the Utrogestan + hMG protocol compared with 0.79% (2/253) in the short protocol. No early neonatal death or intrauterine death were recorded in either group. To date, the data do not indicate an elevated rate of abnormality at birth after progesterone use during ovarian stimulation but further study with larger populations is needed to confirm these results.

  9. Cloning, mapping and molecular characterization of porcine progesterone receptor membrane component 2 (PGRMC2 gene

    Directory of Open Access Journals (Sweden)

    Congying Chen

    2010-01-01

    Full Text Available Progesterone plays an important role in sow reproduction by stimulating classic genomic pathways via nuclear receptors and non-genomic pathways via membrane receptors such a progesterone receptor membrane component 2 (PGRMC2. In this work, we used radiation hybrid mapping to assign PGRMC2 to pig chromosome 8 and observed that this receptor has two transcripts in pigs. The full-length cDNA of the large transcript is 1858 bp long and contains a 669-bp open reading frame (ORF encoding a protein of 223 amino acids. The shorter transcript encodes a protein of 170 amino acids. The porcine PGRMC2 gene consists of three exons 446 bp, 156 bp and 1259 bp in length. The promoter sequence is GC-rich and lacks a typical TATA box. Several putative cis-regulatory DNA motifs were identified in the 208-bp upstream genomic region. Five single nucleotide polymorphisms (SNPs were detected in introns* and the 3' UTR. RT-PCR indicated that the PGRMC2 gene is expressed ubiquitously in all pig tissues examined.

  10. Progesterone receptor modulates estrogen receptor-α action in breast cancer

    Science.gov (United States)

    Mohammed, Hisham; Russell, I. Alasdair; Stark, Rory; Rueda, Oscar M.; Hickey, Theresa E.; Tarulli, Gerard A.; Serandour, Aurelien A. A.; Birrell, Stephen N.; Bruna, Alejandra; Saadi, Amel; Menon, Suraj; Hadfield, James; Pugh, Michelle; Raj, Ganesh V.; Brown, Gordon D.; D’Santos, Clive; Robinson, Jessica L. L.; Silva, Grace; Launchbury, Rosalind; Perou, Charles M.; Stingl, John; Caldas, Carlos; Tilley, Wayne D.; Carroll, Jason S.

    2015-01-01

    Summary Progesterone receptor (PR) expression is employed as a biomarker of estrogen receptor-α (ERα) function and breast cancer prognosis. We now show that PR is not merely an ERα-induced gene target, but is also an ERα-associated protein that modulates its behaviour. In the presence of agonist ligands, PR associates with ERα to direct ERα chromatin binding events within breast cancer cells, resulting in a unique gene expression programme that is associated with good clinical outcome. Progesterone inhibited estrogen-mediated growth of ERα+ cell line xenografts and primary ERα+ breast tumour explants and had increased anti-proliferative effects when coupled with an ERα antagonist. Copy number loss of PgR is a common feature in ERα+ breast cancers, explaining lower PR levels in a subset of cases. Our findings indicate that PR functions as a molecular rheostat to control ERα chromatin binding and transcriptional activity, which has important implications for prognosis and therapeutic interventions. PMID:26153859

  11. Levels of Oxidized LDL, Estrogens, and Progesterone in Placenta Tissues and Serum Paraoxonase Activity in Preeclampsia

    Directory of Open Access Journals (Sweden)

    Şerefden Açıkgöz

    2013-01-01

    Full Text Available In vitro literature studies have suggested that atherosclerotic oxidized low density lipoprotein (OxLDL inhibits trophoblast invasion. The objective of this study was to determine the levels of OxLDL and to examine the relationship between antioxidative estradiol, estriol, and prooxidative progestin in normal and preeclamptic placental tissues and measure the serum activity of antioxidative paraoxonase (PON1. The study included 30 preeclamptic and 32 normal pregnant women. OxLDL was determined with ELISA, estradiol, unconjugated estriol, and progesterone that were determined with chemiluminescence method in placental tissues. Serum PON1 activity was determined with spectrophotometric method. Levels of OxLDL (, estriol (, estradiol (, and progesterone ( were lower in the placental tissues of preeclamptic group compared to the normal pregnant women. Serum PON1 activity was higher in preeclamptic group ( and preeclamptic group without intrauterine growth restriction ( compared to normal pregnant women. Tissue estriol of preeclamptic group without/with IUGR (, was lower than the normal group. Results of our study suggest that the events leading to fetoplacental insufficiency lead to a reduction in the levels of estriol limit deposition of OxLDL in placental tissues. The serum PON1 activity is probably important in the inhibition of OxLDL in preeclampsia.

  12. Perinatal exposure to progesterone, estradiol, or mifepristone affects sexual differentiation of behavior in opossums (Monodelphis domestica).

    Science.gov (United States)

    Fadem, Barbara H; Koester, Diana C; Harder, John D

    2010-08-01

    The effects of perinatal exposure to progesterone (P) and estradiol (E) on sexual differentiation of behavior and morphology were examined by treating male and female gray short-tailed opossums on postnatal day 8 with progesterone alone (P), P plus estradiol (E) (PE), the P receptor antagonist mifepristone/RU486 (MIF), or corn oil control (C) and gonadectomizing them before puberty. When given female hormone replacement therapy in adulthood and tested with intact stimulus males, MIF animals showed less female-typical aggressive threat behavior than animals in other treatment groups. Stimulus males scent marked in more tests involving females than males and in more tests involving MIF animals than animals in other treatment groups. Body weight was lower in females than in males and was lower in MIF animals than in animals in other treatment groups, and P females failed to show female-typical genital locks after copulation. Sexual receptivity was similar in males and females and, while not decreased by any perinatal hormone treatment, was higher in PE males than in animals of either sex in any treatment group. These findings suggest that perinatal exposure to P is associated with the organization of feminine threat behavior and the defeminization of attractivity, body weight and genital anatomy in this marsupial. Reasons for these findings and for why female sexual receptivity is enhanced by perinatal exposure to exogenous E only in an endogenous masculine environment are discussed. Copyright 2010 Elsevier Inc. All rights reserved.

  13. Alcohols which have been in contact with any plastics may interfere in radioimmunoassays of progesterone.

    Science.gov (United States)

    Ocvirk, Rok; Bisson, Jennifer M; Murphy, Beverley E Pearson

    2009-01-01

    In recent years there has been increasing use of plastic rather than glass containers for many liquids, including wine. However we have found that residue from commercially obtained 'pure' ethanol dispensed in plastic bottles interferes in some biochemical assays. We have observed a volume-dependent decrease in maximally bound ligand in radioimmunoassays of progesterone. The resulting shift in the standard curve leads to an underestimation of the analyte concentrations and to altered estimation of cross reactivity by competing ligands. These effects became apparent in assays with high sensitivity (500 pg or less). All sources of ethanol obtainable in Quebec contained impurities. A similar effect was also produced by 'pure' methanol. The reduction in maximally bound ligand was amplified when the alcohol was aliquoted using plastic pipette tips. We conclude that alcohols which have had any contact with plastics are not safe to use in immunoassays of progesterone (or its metabolites as estimated according to cross-reactivity after HPLC) and may affect other assays. If the use of alcohol and plastic tips cannot be avoided, the amount of alcohol used should be reduced to 1% or less. This can be accomplished by preparing steroid standards in assay buffers containing albumin or gelatin, which enhance the solubility of steroids in aqueous media.

  14. 'Luteal coasting' after GnRH agonist trigger - individualized, HCG-based, progesterone-free luteal support in 'high responders'

    DEFF Research Database (Denmark)

    Kol, Shahar; Breyzman, Tatiana; Segal, Linoy

    2015-01-01

    This study reports 21 IVF cases with excessive ovarian response, who received gonadotrophin-releasing hormone agonist (GnRHa) triggering for final oocyte maturation, followed by a human chorionic gonadotrophin (HCG)-based, progesterone-free, luteal support, individually timed ('luteal coasting...... post GnRHa trigger, the same principle that holds for follicular coasting, used in the context of OHSS prevention, may be valid. Monitoring luteal progesterone concentrations from the day of oocyte retrieval, and administering a bolus of HCG (1500 IU) when the concentration drops significantly, seems...

  15. Circulating levels of prolactin and progesterone in a wild population of red kangaroos (Macropus rufus) Marsupialia: Macropodidae

    Science.gov (United States)

    Muths, E.; Hinds, L. A.

    1996-01-01

    Circulating progesterone and prolactin levels were measured in shot and live-caught wild red kangaroos using radioimmunoassays validated for the red kangaroo. The objective of the study was to correlate hormone profiles with reproductive status and determine if red kangaroos follow the general pattern elucidated for other macropodids. During Phase 2a lactation (600 pg/ml (n= 32) during the transition to Phase 3 lactation (181 to 235 days) when the quiescent corpus luteum and embryo were reactivated. Progesterone concentrations then decreased to kangaroos follow patterns found previously in other macropodid species, the tammar and Bennett's wallabies.

  16. Successful treatment of low-grade endometrial cancer in premenopausal women with an aromatase inhibitor after failure with oral or intrauterine progesterone.

    Science.gov (United States)

    Straubhar, Alli; Soisson, Andrew P; Dodson, Mark; Simons, Elise

    2017-08-01

    Young women with endometrial intraepithelial hyperplasia or low-grade endometrial carcinoma are potential candidates for conservative fertility sparing therapy utilizing progesterone rather than hysterectomy. High-dose progesterone treatment is associated with 55-80% initial response but high relapse rates. Using aromatase inhibitors in conjunction with high-dose progesterone has largely been unstudied. Three obese premenopausal women with endometrial cancer failed to respond to oral or intrauterine progesterone as first line therapy. Due to their desire to continue to pursue fertility sparing treatment options, an aromatase inhibitor was added to their treatment regimen. This resulted in resolution of their malignancy in each case. In obese premenopausal women, the mechanism of malignant transformation in endometrial carcinoma is considered to be an association with relatively high levels of serum estrogen from peripheral conversion of androgens to estrone in adipose tissue with a deficiency in progesterone exposure due to chronic anovulation. Using aromatase inhibitors seems reasonable as an adjunct to progesterone given the high likelihood that this population has a significant proportion of their estrogen production coming from peripheral conversion in adipose tissue. This case series is unique in that each woman initially failed to respond to progesterone but had resolution when an aromatase inhibitor was added to their treatment regimen. This would suggest that obese women with low grade malignancy or hyperplasia who have no radiographic evidence of deep myometrial invasion, ovarian or retroperitoneal metastases and who wish to retain their fertility may be treated with intrauterine progesterone and an aromatase inhibitor.

  17. Selective progesterone receptor modulator (SPRM) ulipristal acetate (UPA) and its effects on the human endometrium

    Science.gov (United States)

    Whitaker, L.H.R.; Murray, A.A.; Matthews, R.; Shaw, G.; Williams, A.R.W.; Saunders, P.T.K.

    2017-01-01

    Abstract STUDY QUESTION What is the impact of administration of the selective progesterone receptor modulator (SPRM), ulipristal acetate (UPA) on the endometrium of women with fibroids? SUMMARY ANSWER UPA administration altered expression of sex-steroid receptors and progesterone-regulated genes and was associated with low levels of glandular and stromal cell proliferation. WHAT IS KNOWN ALREADY Administration of all SPRM class members results in PAEC (progesterone receptor modulator associated endometrial changes). Data on the impact of the SPRM UPA administration on endometrial sex-steroid receptor expression, progesterone (P)-regulated genes and cell proliferation are currently lacking. STUDY DESIGN SIZE, DURATION Observational study with histological and molecular analyses to delineate impact of treatment with UPA on endometrium. Endometrial samples (n = 9) were collected at hysterectomy from women aged 39 to 49 with uterine fibroids treated with UPA (oral 5 mg daily) for 9–12 weeks. Control proliferative (n = 9) and secretory (n = 9) endometrium from women aged 38–52 with fibroids were derived from institutional tissue archives. PARTICIPANTS/MATERIALS, SETTING, METHODS Study setting was a University Research Institute. Endometrial biopsies were collected with institutional ethical approval and written informed consent. Concentrations of mRNAs encoded by steroid receptors, P-regulated genes and factors in decidualised endometrium were quantified with qRT-PCR. Immunohistochemistry was employed for localization of progesterone (PR, PRB), androgen (AR), estrogen (ERα) receptors and expression of FOXO1, HAND2, HOXA10, PTEN homologue. Endometrial glandular and stromal cell proliferation was objectively quantified using Ki67. MAIN RESULTS AND THE ROLE OF CHANCE UPA induced morphological changes in endometrial tissue consistent with PAEC. A striking change in expression patterns of PR and AR was detected compared with either proliferative or secretory phase

  18. Dehydroepiandrosterone (DHEA) supplementation results in supraphysiologic DHEA-S serum levels and progesterone assay interference that may impact clinical management in IVF.

    Science.gov (United States)

    Franasiak, Jason M; Thomas, Semara; Ng, Susan; Fano, Maria; Ruiz, Andrew; Scott, Richard T; Forman, Eric J

    2016-03-01

    Dehydroepiandrosterone (DHEA) is often prescribed for poor responders in IVF in an effort to improve response to ovarian stimulation. The effect of DHEA supplementation and resultant supraphysiologic DHEA-S serum levels on sex steroid assays has not been evaluated in this population. This study seeks to determine the relationship between DHEA supplementation and progesterone measurements to characterize the degree of interference with particular immunoassays. Characterization was accomplished in two phases. First, DHEA-S standard control reagents with no progesterone present were assayed for both DHEA-S and progesterone levels. Second, serum pools from 60 unique IVF patients' serum were used to create six pooled serum samples: three from patients on DHEA supplementation and three from patients not on DHEA supplementation. The three pools were composed of patients whose serum fell into low, medium, and high progesterone ranges. Baseline DHEA-S and progesterone were measured, and the mean level of DHEA-S in the mid-range progesterone pool was used as the mid-point for addition of DHEA-S standard to the serum pools from patients without DHEA supplementation. Progesterone from these pools was then measured on three commercially available immunoassay systems. The first experiment revealed a linear increase in progesterone when analyzing the DHEA-S standard ranging from 0.5 ng/mL in the blank control (no DHEA-S) to up to 2.0 ng/mL in the high control (DHEA-S >700 μg/mL), indicating that the DHEA-S cross-reacts with the progesterone assays. In the second experiment, patients' serum DHEA-S and progesterone were measured from pooled serum samples of those taking DHEA and those not taking DHEA. Adding DHEA-S to the pooled serum of those not taking DHEA resulted in a linear increase in progesterone levels on two of three commercially available immunoassays (p DHEA-S can interfere with standard progesterone immunoassays used in clinical ART programs, and thus serum

  19. A membrane-associated progesterone-binding protein, 25-Dx, is regulated by progesterone in brain regions involved in female reproductive behaviors

    Science.gov (United States)

    Krebs, Christopher J.; Jarvis, Erich D.; Chan, Johnny; Lydon, John P.; Ogawa, Sonoko; Pfaff, Donald W.

    2000-01-01

    The ventromedial hypothalamus (VMH) plays a central role in the regulation of the female reproductive behavior lordosis, a behavior dependent upon the sequential activation of receptors for the ovarian steroid hormones estradiol (E) and progesterone (P). These receptors function as transcription factors to alter the expression of target genes. To discover behaviorally relevant genes targeted by E and P in the VMH, we used the differential display PCR to identify messenger RNAs that are differentially expressed in the hypothalamus of ovariectomized (ovx) rats treated with E alone compared with ovariectomized rats treated with E and P. We show here that one interesting mRNA within the hypothalamus that is repressed by P after E priming encodes the protein 25-Dx, the rat homolog of the human membrane-associated P-binding protein Hpr6.6. Neurons in the brain containing the highest levels of 25-Dx are located in several nuclei of the basal forebrain, including the VMH. 25-Dx expression is also higher in the hypothalamus of female P receptor “knockout” mice than in their wild-type littermates. These findings suggest a mechanism in which the activation of nuclear P receptor represses expression of a membrane P receptor, 25-Dx, during lordosis facilitation. PMID:11070092

  20. Effect of gonadorelin, lecirelin, and buserelin on LH surge, ovulation, and progesterone in cattle.

    Science.gov (United States)

    Picard-Hagen, N; Lhermie, G; Florentin, S; Merle, D; Frein, P; Gayrard, V

    2015-07-15

    Analogs of gonadoliberin (GnRH) are widely used in cattle to synchronize estrus and to induce ovulation, as well as for the treatment of ovarian cysts. The aim of this study was to compare the plasma profiles of LH and progesterone and the follicular dynamics in response to the administration of gonadorelin, lecirelin, or buserelin at the dose recommended to induce ovulation. In addition, the biological response to a half dose of lecirelin was assessed. Twelve healthy Holstein female cows were divided into four sequence groups, according to a Latin square design and received the four treatments during the four periods of the study. Before each period, the estrous cycle was synchronized, and on Day 6 or 7 of the ensuing cycle, the time at which it was most likely to have a dominant follicle, 100 μg of gonadorelin, 25 μg of lecirelin, 50 μg of lecirelin, or 10 μg of buserelin was administered to the cows. Blood samples were regularly collected for up to 4 days after the GnRH administrations. The plasma LH response was evaluated for up to 6 hours after administration, and the plasma progesterone response and ovarian follicular dynamics were evaluated for up to 4 days. There was a significantly lower LH release after gonadorelin treatment compared to lecirelin at the doses of 25 or 50 μg and the buserelin treatment. The mean maximal LH concentration after gonadorelin treatment was 2.5 lower than after lecirelin or buserelin treatment and was reached 1 hour earlier. Four days after the GnRH administration (i.e., at Days 10-11 of the estrous cycle), the overall mean increase in plasma progesterone concentration was 70% and did not differ between the treatment groups. The percentage of disappearance of the dominant follicle (84.8% of ovulation and 4.3% of luteinization) after GnRH treatment was high (73%, 82%, 100%, and 100%, for gonadorelin, lecirelin at the doses of 25 and 50 μg, and buserelin, respectively) and did not differ between the GnRH treatments. The

  1. Progesterone withdrawal. II: insensitivity to the sedative effects of a benzodiazepine.

    Science.gov (United States)

    Moran, M H; Goldberg, M; Smith, S S

    1998-10-05

    Previous results from this lab have demonstrated that the GABA-modulatory steroid 3alpha-OH-5alpha-pregnan-20-one (3alpha, 5alpha-THP) exhibits withdrawal properties, increasing anxiety [M.A. Gallo, S.S. Smith, Progesterone withdrawal decreases latency to and increases duration of electrified prod burial: a possible rat model of PMS anxiety, Pharmacol. Biochem. 46 (1993) 897-904.] and seizure susceptibility [S.S. Smith, Q.H. Gong, F.-C. Hsu, R.S. Markowitz, J. M.H. ffrench-Mullen, X. Li, GABAA receptor alpha4 subunit suppression prevents withdrawal properties of an endogenous steroid, Nature 392 (1998) 926-930.] upon abrupt discontinuation after chronic administration of its parent compound, progesterone (P), in a manner similar to other GABA-modulatory drugs. Further, we have demonstrated that withdrawal from P produces insensitivity to the potentiating effects of the benzodiazepine (BDZ) lorazepam (LZM) on GABA-gated Cl- current [A.-M.N. Costa, K.T. Spence, S.S. Smith, J.M. H. ffrench-Mullen, Withdrawal from the endogenous steroid progesterone results in GABAA currents insensitive to BDZ modulation in rats CA1 hippocampus, J. Neurophysiology 74 (1995) 464-469; S.S. Smith, Q.H. Gong, F.-C. Hsu, R.S. Markowitz, J.M.H. ffrench-Mullen, X. Li, GABAA receptor alpha4 subunit suppression prevents withdrawal properties of an endogenous steroid, Nature 392 (1998) 926-930.], assessed using whole cell patch clamp procedures on pyramidal neurons acutely dissociated from CA1 hippocampus. The purpose of the present study was to examine the withdrawal effects of P on the sedative potency of LZM, tested behaviorally as the ability to maintain position on a variable speed treadmill following LZM administration (0.75 mg/kg). Both continuous (continuous release P capsule, single withdrawal) as well as discontinuous (multiple P injection, multiple withdrawal) paradigms were tested. Longer continuous release paradigms were more effective in abolishing the sedative effects of LZM

  2. Progesterone receptor membrane component 1 deficiency attenuates growth while promoting chemosensitivity of human endometrial xenograft tumors.

    Science.gov (United States)

    Friel, Anne M; Zhang, Ling; Pru, Cindy A; Clark, Nicole C; McCallum, Melissa L; Blok, Leen J; Shioda, Toshi; Peluso, John J; Rueda, Bo R; Pru, James K

    2015-01-28

    Endometrial cancer is the leading gynecologic cancer in women in the United States with 52,630 women predicted to be diagnosed with the disease in 2014. The objective of this study was to determine if progesterone (P4) receptor membrane component 1 (PGRMC1) influenced endometrial cancer cell viability in response to chemotherapy in vitro and in vivo. A lentiviral-based shRNA knockdown approach was used to generate stable PGRMC1-intact and PGRMC1-deplete Ishikawa endometrial cancer cell lines that also lacked expression of the classical progesterone receptor (PGR). Progesterone treatment inhibited mitosis of PGRMC1-intact, but not PGRMC1-deplete cells, suggesting that PGRMC1 mediates the anti-mitotic actions of P4. To test the hypothesis that PGRMC1 attenuates chemotherapy-induced apoptosis, PGRMC1-intact and PGRMC1-deplete cells were treated in vitro with vehicle, P4 (1 µM), doxorubicin (Dox, 2 µg/ml), or P4 + Dox for 48 h. Doxorubicin treatment of PGRMC1-intact cells resulted in a significant increase in cell death; however, co-treatment with P4 significantly attenuated Dox-induced cell death. This response to P4 was lost in PGRMC1-deplete cells. To extend these observations in vivo, a xenograft model was employed where PGRMC1-intact and PGRMC1-deplete endometrial tumors were generated following subcutaneous and intraperitoneal inoculation of immunocompromised NOD/SCID and nude mice, respectively. Tumors derived from PGRMC1-deplete cells grew slower than tumors from PGRMC1-intact cells. Mice harboring endometrial tumors were then given three treatments of vehicle (1:1 cremophor EL: ethanol + 0.9% saline) or chemotherapy [Paclitaxel (15 mg/kg, i.p.) followed after an interval of 30 minutes by CARBOplatin (50 mg/kg)] at five day intervals. In response to chemotherapy, tumor volume decreased approximately four-fold more in PGRMC1-deplete tumors when compared with PGRMC1-intact control tumors, suggesting that PGRMC1 promotes tumor cell viability

  3. Relationships between Milk Progesterone Profiles and Genetic Merit for Milk Production, Milking Frequency, and Feeding Regimen in Dairy Cattle

    NARCIS (Netherlands)

    Windig, J.J.; Beerda, B.; Veerkamp, R.F.

    2008-01-01

    Milk progesterone profiles were determined from samples obtained twice weekly for 100 d postpartum in 100 Holstein primiparous cows at a Dutch experimental farm. Three treatments were applied in a 2 x 2 x 2 factorial arrangement with high-low genetic merit for overall production, high-low caloric

  4. Effects of endogenous and exogenous progesterone on emotional intelligence in cocaine-dependent men and women who also abuse alcohol.

    Science.gov (United States)

    Milivojevic, Verica; Sinha, Rajita; Morgan, Peter T; Sofuoglu, Mehmet; Fox, Helen C

    2014-11-01

    As sex differences in substance dependence may impinge upon the perception and regulation of emotion, we assess emotional intelligence (EI) as a function of gender, menstrual cycle (MC) phase and hormonal changes in early abstinent cocaine-dependent individuals who abuse alcohol (CDA). Study 1: The Mayer, Salovey, and Caruso Emotional Intelligence Test (MSCEIT) was administered to 98 CDA (55 M/43 F) and 56 healthy (28 M/28 F) individuals. Performance in women was also assessed by MC phase. Study 2: The MSCEIT was administered to 28 CDA (19 M/9 F) who received exogenous progesterone (400 mg/day) versus placebo for 7 days (study 2). Study 1: Healthy females were better than healthy males at facilitating thought and managing emotions. This gender discrepancy was not observed in the CDA group. Additionally, all women in the high compared with the low progesterone phase of their MC were better at managing their emotions. Study 2: Exogenous progesterone improved ability to facilitate thought in both males and females. CDA women may be vulnerable to difficulties managing and regulating emotions. Gonadal hormones may contribute to this gender effect, as increases in both endogenous and exogenous progesterone improved selective aspects of EI. Copyright © 2014 John Wiley & Sons, Ltd.

  5. Progesterone Withdrawal Reduces Paired-Pulse Inhibition in Rat Hippocampus: Dependence on GABAA Receptor α4 Subunit Upregulation

    National Research Council Canada - National Science Library

    Fu-Chun Hsu; Sheryl S. Smith

    2003-01-01

    Withdrawal from the endogenous steroid progesterone (P) after chronic administration increases anxiety and seizure susceptibility via declining levels of its potent GABA-modulatory metabolite 3α-OH-5α-pregnan-20-one (3α,5αTHP). This 3α,5α...

  6. Effects of endogenous and exogenous progesterone on emotional intelligence in cocaine dependent men and women who also abuse alcohol

    Science.gov (United States)

    Milivojevic, V; Sinha, R; Morgan, PT; Sofuoglu, M; Fox, HC

    2015-01-01

    Objective As sex differences in substance dependence may impinge upon the perception and regulation of emotion, we assess Emotional Intelligence (EI) as a function of gender, menstrual cycle (MC) phase and hormonal changes in early abstinent cocaine dependent individuals who abuse alcohol (CDA). Methods Study 1: The Mayer, Salovey, and Caruso Emotional Intelligence Test (MSCEIT) was administered to 98 CDA (55M/43F) and 56 healthy (28M/28F) individuals. Performance in women was also assessed by MC phase. Study 2: The MSCEIT was administered to 18 CDA (19M/9F) who received exogenous progesterone (400mg/day) versus placebo for 7 days. (Study 2). Results Study 1: Healthy females were better than healthy males at facilitating thought and managing emotions. This gender discrepancy was not observed in the CDA group. Additionally, all women in the high compared with the low progesterone phase of their MC were better at managing their emotions. Study 2: Exogenous progesterone improved ability to facilitate thought in both males and females. Conclusions CDA women may be vulnerable to difficulties managing and regulating emotions. Gonadal hormones may contribute to this gender effect, as increases in both endogenous and exogenous progesterone improved selective aspects of EI. PMID:25363303

  7. Population differences and the effect of vaginal progesterone on preterm birth in women with threatened preterm labor*

    NARCIS (Netherlands)

    Hermans, Frederik Jan Robin; Karolinski, Ariel; Othenin-Girard, Véronique; Bertolino, María Victoria; Schuit, Ewoud; Salgado, Pablo; Hösli, Irene; Irion, Olivier; Laterra, Cristina; Mol, Ben Willem J; Martinez de Tejada, Begoña

    2016-01-01

    Objective: Threatened preterm labor (tPTL) is a complication of pregnancy. Identification of women and clinical definition differs between countries. This study investigated differences in tPTL and effectiveness of vaginal progesterone to prevent preterm birth (PTB) between two countries. Methods:

  8. 'Luteal coasting' after GnRH agonist trigger - individualized, HCG-based, progesterone-free luteal support in 'high responders'

    DEFF Research Database (Denmark)

    Kol, Shahar; Breyzman, Tatiana; Segal, Linoy

    2015-01-01

    This study reports 21 IVF cases with excessive ovarian response, who received gonadotrophin-releasing hormone agonist (GnRHa) triggering for final oocyte maturation, followed by a human chorionic gonadotrophin (HCG)-based, progesterone-free, luteal support, individually timed ('luteal coasting') ...

  9. The inhibitory effect of progesterone on lactogenesis during pregnancy is already evident by mid- to late gestation in rodents.

    Science.gov (United States)

    López-Fontana, Constanza M; Maselli, María E; Salicioni, Ana M; Carón, Rubén W

    2012-01-01

    Lactogenesis is a very complex process highly dependent on hormonal regulation. In the present study the time-course of the inhibitory actions of progesterone on prolactin secretion, mammary gland morphology and lactogenesis from mid- to late gestation in rodents was investigated. Groups of pregnant rats were luteectomised or administered with mifepristone on Day 10, 13, 15 or 17 of gestation and decapitated 28 or 48h later. Whole-blood samples and the inguinal mammary glands were taken for determinations of hormone levels and for measurement of mammary content of casein and lactose and for tissue morphology analyses, respectively. Luteectomy or mifepristone evoked prolactin increases only after Day 17 of gestation. Mammary content of casein was increased by both treatments regardless of timing or duration. Mifepristone was less effective than luteectomy in inducing lactose production and the effect was only observed after Day 15 of gestation. Analysis of mammary gland morphology confirmed the observed effect of progesterone on lactogenesis. Both treatments triggered remarkable secretory activity in the mammary gland, even without a parallel epithelial proliferation, demonstrating that the mammary epithelium is able to synthesise milk compounds long before its full lobulo-alveolar development is achieved, provided that progesterone action is abolished. Thus, the present study demonstrates that progesterone is a potent hormonal switch for the prolactin and prolactin-like effects on mammary gland development and its milk-synthesising capacity during pregnancy, and that its inhibitory action is already evident by mid-pregnancy in rodents.

  10. RESCUE OF BROMODICHLOROMETHANE-INDUCED PREGNANCY LOSS IN THE F344 RAT BY EXOGENOUS PROGESTERONE AND HCG

    Science.gov (United States)

    Rescue of bromodichloromethane-induced pregnancy loss in the F344 rat by exogenous progesterone and hCG.Susan R. Bielmeier1, Deborah S. Best2 and Michael G. Narotsky21 Curriculum in Toxicology, Univ. of North Carolina, Chapel Hill, NC, USA2 Reproductive Toxico...

  11. Regulation of the membrane structure by brassinosteroids and progesterone in winter wheat seedlings exposed to low temperature

    Czech Academy of Sciences Publication Activity Database

    Filek, M.; Rudolphi-Skórska, E.; Sieprawska, A.; Kvasnica, Miroslav; Janeczko, A.

    2017-01-01

    Roč. 128, DEC (2017), s. 37-45 ISSN 0039-128X R&D Projects: GA ČR GJ15-08202Y Institutional support: RVO:61389030 Keywords : 24-Epibrassinolide * 24-Epicastasterone * Galactolipids * Phospholipids * Progesterone * Seedlings * Winter wheat Subject RIV: CC - Organic Chemistry Impact factor: 2.282, year: 2016

  12. Scientific Message Translation and the Heuristic Systematic Model: Insights for Designing Educational Messages About Progesterone and Breast Cancer Risks.

    Science.gov (United States)

    Hitt, Rose; Perrault, Evan; Smith, Sandi; Keating, David M; Nazione, Samantha; Silk, Kami; Russell, Jessica

    2016-06-01

    Results of ongoing scientific research on environmental determinants of breast cancer are not typically presented to the public in ways they can easily understand and use to take preventive actions. In this study, results of scientific studies on progesterone exposure as a risk factor for breast cancer were translated into high and low literacy level messages. Using the heuristic systematic model, this study examined how ability, motivation, and message processing (heuristic and systematic) influenced perceptions of risk beliefs and negative attitudes about progesterone exposure among women who read the translated scientific messages. Among the 1254 participants, those given the higher literacy level message had greater perceptions of risk about progesterone. Heuristic message cues of source credibility and perceived message quality, as well as motivation, also predicted risk beliefs. Finally, risk beliefs were a strong predictor of negative attitudes about exposure to progesterone. The results can help improve health education message design in terms of practitioners having better knowledge of message features that are the most persuasive to the target audiences on this topic.

  13. Identification and partial characterization of Rhizopus nigricans Gβ proteins and their expression in the presence of progesterone.

    Science.gov (United States)

    Jeraj, Nataša; Stilla, Annalisa; Petrič, Spela; Di Girolamo, Maria; Crešnar, Bronislava; Lenasi, Helena

    2012-03-01

    The mammalian steroid hormone progesterone actuates a signalling pathway in the zygomycete Rhizopus nigricans which includes heterotrimeric G proteins. To investigate the possibility that the Gβ subunit of these proteins is involved in the signalling, a cDNA library from R. nigricans exposed to progesterone was prepared and a sequence coding for a Gβ subunit was searched for. Using degenerate primers, two sequences, RnGPB1 and RnGPB2, were identified that exhibited a high degree of identity with those for Gβ from other filamentous fungi, but not from yeast. The presence of more than one Gβ subunit is very rare among the fungi, and it has been to date reported only for Rhizopus oryzae. We have shown that progesterone increases the expression of RnGPB1, but has no influence on the expression of RnGPB2. Therefore, our studies imply the involvement of Gβ subunit 1 in the response of R. nigricans to progesterone. Moreover, the Gβ subunit is subjected to endogenous ADP-ribosylation in the presence of NAD, which could be important in some, as yet unknown, cell process. Article from a special issue on steroids and microorganisms. Copyright © 2011 Elsevier Ltd. All rights reserved.

  14. Progesterone profiles around the time of insemination do not show clear differences between of pregnant and not pregnant dairy cows

    DEFF Research Database (Denmark)

    Gorzecka, Justyna; Codrea, Marius Cosmin; Friggens, Nicolas C

    2011-01-01

    differences between the groups. However, the analysis correctly classified 75% of true pregnant cows. Conversely, only 60% of not pregnant animals were classified as such by the discriminate analysis. Individual analysis of progesterone profile features in pregnant and not pregnant groups of estrous cycles...

  15. Intrahepatic cholestasis of pregnancy: Amelioration of pruritus by UDCA is associated with decreased progesterone disulphates in urine.

    Science.gov (United States)

    Glantz, Anna; Reilly, Sarah-Jayne; Benthin, Lisbet; Lammert, Frank; Mattsson, Lars-Ake; Marschall, Hanns-Ulrich

    2008-02-01

    Intrahepatic cholestasis of pregnancy (ICP) is characterized by pruritus, elevated bile acids, and, specifically, elevated disulphated progesterone metabolites. We aimed to study changes in these parameters during treatment with dexamethasone or ursodeoxycholic acid (UDCA) in 40 out of 130 women included in the Swedish ICP intervention trial (26 randomized to placebo or UDCA, 14 randomized to dexamethasone). Serum bile acid profiles and urinary steroid hormone metabolites were analyzed using isotope-dilution gas chromatography-mass spectrometry and electrospray-mass spectrometry. We found that all patients displayed ICP-typical serum bile acid profiles with >50% cholic acid at baseline but almost 80% UDCA upon treatment with this bile acid. In UDCA-treated patients, relative amounts of disulphated progesterone metabolites in urine decreased by 34%, 48% (P acid levels. In contrast, in patients randomized to dexamethasone or placebo, no changes in steroid metabolites or pruritus scores were observed. UDCA treatment in ICP decreased urinary excretion of disulphated progesterone metabolites, suggesting that amelioration of pruritus is connected to stimulation of hepatobiliary excretion of progesterone disulphates.

  16. Endometrial Receptivity Profile in Patients with Premature Progesterone Elevation on the Day of hCG Administration

    Directory of Open Access Journals (Sweden)

    Delphine Haouzi

    2014-01-01

    Full Text Available The impact of a premature elevation of serum progesterone level, the day of hCG administration in patients under controlled ovarian stimulation during IVF procedure, on human endometrial receptivity is still debated. In the present study, we investigated the endometrial gene expression profile shifts during the prereceptive and receptive secretory stage in patients with normal and elevated serum progesterone level on the day of hCG administration in fifteen patients under stimulated cycles. Then, specific biomarkers of endometrial receptivity in these two groups of patients were tested. Endometrial biopsies were performed on oocyte retrieval day and on day 3 of embryo transfer, respectively, for each patient. Samples were analysed using DNA microarrays and qRT-PCR. The endometrial gene expression shift from the prereceptive to the receptive stage was altered in patients with high serum progesterone level (>1.5 ng/mL on hCG day, suggesting accelerated endometrial maturation during the periovulation period. This was confirmed by the functional annotation of the differentially expressed genes as it showed downregulation of cell cycle-related genes. Conversely, the profile of endometrial receptivity was comparable in both groups. Premature progesterone rise alters the endometrial gene expression shift between the prereceptive and the receptive stage but does not affect endometrial receptivity.

  17. Evaluating the interaction between progesterone, TNF alpha and cortisol on early loss of transferred embryos in beef cows

    Science.gov (United States)

    Fifty-eight non-lactating cows previously synchronized for estrus were assigned to two treatments to assess the effects of progesterone supplementation and its correlation with TNF-a and cortisol on the survival of the transferred embryos. On day 7 after exhibiting estrus (day 0), cows in both group...

  18. 17 beta-estradiol and progesterone do not influence the production of cytokines from lipopolysaccharide-stimulated monocytes in humans

    NARCIS (Netherlands)

    Schipper, M; Heineman, MJ; Faas, M; Bouman, A.

    2004-01-01

    Objective: To test whether 17beta-estradiol or progesterone influence the cytokine productive capacity of lipopolysaccharide (LPS)-stimulated monocytes in humans. Design: Prospective study. Setting: Academic research institution. Patient(s): Seven women in the luteal phase of a normal ovarian cycle,

  19. Ultrasonography and hormone profiles of persistent ovarian follicles (cysts) induced with low doses of progesterone in cattle.

    Science.gov (United States)

    Noble, K M; Tebble, J E; Harvey, D; Dobson, H

    2000-11-01

    The aims of this study were to expose dominant ovarian follicles at the end of the oestrous cycle to low progesterone concentrations similar to those that occur during stress, and to examine the effect of a subsequent small increase in progesterone 10 days later. Half a progesterone releasing intravaginal device (0.5 PRID) was administered to 13 heifers from day 15 of the oestrous cycle. In group 1 (n = 7), one 0.5 PRID remained in place until day 40 or until each heifer ovulated. In group 2 (n = 6), the first 0.5 PRID was removed on day 28, and replaced immediately with a second 0.5 PRID. Ultra-sonography and blood collection (10 ml) were conducted each day for 26 days from day 14 and then on alternate days. The largest follicle that emerged during the first 5 days after insertion of the initial 0.5 PRID remained > 10 mm in diameter for 15.3 +/- 1.7 and 11.6 +/- 0.4 days in groups 1 and 2, respectively. This period of dominance, during which no other follicles emerged, was closely correlated with the duration of plasma oestradiol concentrations exceeding 10 pg ml(-1). In four heifers from group 1, the persistent follicle ovulated between days 30 and 37 (sub-group 1a; 0.5 PRID expelled). In three heifers from sub-group 1b (0.5 PRID retained), the dominant follicle secreted oestradiol for 17 +/- 5 days but remained detectable by ultrasonography for a total of 33 +/- 8 days (range 26-52 days). Monitoring continued beyond day 40 in these animals. In group 2, the new 0.5 PRID inserted on day 28 resulted in an increase in plasma progesterone concentration of 0.9 +/- 0.3 ng ml(-1). Simultaneously, oestradiol decreased by 10.1 +/- 3.3 pg ml(-1), and a new follicular wave emerged 5-7 days later. In conclusion, exposure to very low concentrations of progesterone produced persistent follicles that secreted oestradiol for 17 days. This oestradiol production could be disrupted by a second increase of 0.9 ng ml(-1) in peripheral progesterone concentration. In the absence of the

  20. Impact of sample extraction on the accurate measurement of progesterone in human serum by liquid chromatography tandem mass spectrometry.

    Science.gov (United States)

    Ke, Yuyong; Gonthier, Renaud; Labrie, Fernand

    2017-05-01

    In the present study, the impact of the extraction solvent on the accuracy of endogenous progesterone assay in human serum has been investigated using two selective reaction monitoring (SRM) transitions (315>97 & 315>109). Higher levels of noise and more interference were observed when more polar solvents were used for extraction, thus resulting in serious bias of the measured values of progesterone in serum. This is confirmed by monitoring the ion ratio of 315>97-315>109. This issue could not be easily resolved by changes in MS/MS transitions or chromatography conditions. More bias was observed with the SRM transition 315>109 for the polar solvent extraction. Hexane and 1-chlorobutane (polarity index of 0 and 1, respectively) did provide the cleanest samples with a lower noise level in the chromatograms. Moreover, the measured values of progesterone were not changed with different SRM transitions or longer retention time in search of an improved separation. Recovery tests of progesterone have been performed with 1-chlorobutane in matrices with phosphate buffered saline (PBS) 1x, PBS 1×3% bovine serum albumin (BSA), stripped serum/H2O (1:1) and unstripped serum. The recovery (70%∼80%) consistency is observed not only at different levels but also in different matrices. The equivalent recovery between PBS 1x, PBS 1×3% BSA and unstripped serum shows that the impact of progesterone binding to serum proteins on the measurement accuracy can be avoided with this sample preparation procedure. No significant matrix effect on the determination of progesterone was observed with 1-chlorobutane. Within the range of 12.5-2000pg/mL, a good linearity is observed with R>0.99 and weighting factor 1/X. Bias and covariance efficiency of QCs are within 10%. With 1-chlorobutane as the extraction solvent, the concentration of progesterone was measured where the range for postmenopausal serum is 5.74∼91.7pg/mL, which is well below the reported concentrations of 314 pg/mL∼942pg

  1. Reduced progesterone and altered cotyledonary prostaglandin values induced by locoweed (Astragalus lentiginosus) in sheep

    Energy Technology Data Exchange (ETDEWEB)

    Ellis, L.C.; James, L.F.; McMullen, R.W.; Panter, K.E.

    1985-09-01

    Feeding 300 or 400 g of dried spotted locoweed, Astragalus lentiginosus per day to 11 pregnant Columbia ewes from the 20th to the 50th days of their gestations resulted in dead and edematous fetuses. Aspartate aminotransferase values were increased, whereas serum progesterone values were significantly diminished in a dose-dependent manner by locoweed ingestion. Cotyledonary 6-keto-prostaglandin (PG)F1 alpha (400 g/day only) and PGF2 alpha (300 and 400 g/day) values were significantly increased, whereas PGE values were not affected by the treatment. Alterations in PG values in these sheep may be a mechanism for altering corpus luteum function and inducing fetal death, which would ultimately result in abortion.

  2. Autoimmune progesterone dermatitis in a patient with endometriosis: case report and review of the literature

    Directory of Open Access Journals (Sweden)

    Baldwin James L

    2004-08-01

    Full Text Available Abstract Autoimmune progesterone dermatitis (APD is a condition in which the menstrual cycle is associated with a number of skin findings such as urticaria, eczema, angioedema, and others. In affected women, it occurs 3–10 days prior to the onset of menstrual flow, and resolves 2 days into menses. Women with irregular menses may not have this clear correlation, and therefore may be missed. We present a case of APD in a woman with irregular menses and urticaria/angioedema for over 20 years, who had not been diagnosed or correctly treated due to the variable timing of skin manifestations and menses. In addition, we review the medical literature in regards to clinical features, pathogenesis, diagnosis, and treatment options.

  3. Evaluation of extraction methods for progesterone determination in rabbit (Oryctolagus cuniculus) feces by radioimmunoassay

    Energy Technology Data Exchange (ETDEWEB)

    Korndoerfer, Clotilde Maria; Meirelles, Cyro Ferreira; Bueno, Ives Claudio da Silva; Abdalla, Adibe Luiz [Centro de Energia Nuclear na Agricultura (CENA), Piracicaba, SP (Brazil). Secao de Ciencias Animais]. E-mail: cfmeirel@esalq.usp.br

    1998-07-01

    The purpose of this study was to find a practical procedure for the extraction of progesterone (P{sub 4}) from feces and to determine if the P4 plasma profiles during pregnancy were reflected in total fecal P4 of pregnant rabbits. The rabbit was used as model for the techniques. Plasma and feces were collected from 11 rabbits during a period of 42 days. Three different methods of P4 extraction were used. The total P4 was measured by solid-phase radioimmunoassay (RIA) with {sup 125} I-P4 as the tracer. Results suggested that it was possible to extract total P4 from rabbit feces with methanol and petroleum ether. Plasma and fecal P4 profiles were compared for both pregnant and ovariectomized rabbits. It was possible to differentiate total P4 extracted from day two through 28 after breeding (p<0.01). (author)

  4. Dietary acrylamide intake and estrogen and progesterone receptor-defined postmenopausal breast cancer risk

    DEFF Research Database (Denmark)

    Pedersen, Grete S; Hogervorst, Janneke G F; Schouten, Leo J

    2010-01-01

    Acrylamide, a potential human carcinogen, has been discovered in a variety of heat-treated carbohydrate-rich food products. Previously, dietary acrylamide intake was shown to be associated with endocrine-related cancers in humans. We assessed the association between dietary acrylamide intake...... breast cancer cases were ascertained, with hormone receptor status information for 43%. Cox proportional hazards analysis was applied to determine hazard ratios in quintiles of dietary acrylamide intake stratifying on estrogen receptor (ER) and progesterone receptor (PR) and smoking status...... ratios were 1.31 (95% CI: 0.87-1.97, P (trend) = 0.26) for ER+, 1.47 (0.86-2.51, P (trend) = 0.14) for PR+, and 1.43 (0.83-2.46, P (trend) = 0.16) for ER+PR+, when comparing women in the highest quintile of acrylamide intake (median 36.8 microg/day) to women in the lowest (median 9.5 microg...

  5. Reduced levels of maternal progesterone during pregnancy increase the risk for allergic airway diseases in females only.

    Science.gov (United States)

    Hartwig, Isabel R V; Bruenahl, Christian A; Ramisch, Katherina; Keil, Thomas; Inman, Mark; Arck, Petra C; Pincus, Maike

    2014-10-01

    Observational as well as experimental studies support that prenatal challenges seemed to be associated with an increased risk for allergic airway diseases in the offspring. However, insights into biomarkers involved in mediating this risk are largely elusive. We here aimed to test the association between endogenous and exogenous factors documented in pregnant women, including psychosocial, endocrine, and life style parameters, and the risk for allergic airway diseases in the children later in life. We further pursued to functionally test identified factors in a mouse model of an allergic airway response. In a prospectively designed pregnancy cohort (n = 409 families), women were recruited between the 4th and 12th week of pregnancy. To investigate an association between exposures during pregnancy and the incidence of allergic airway disease in children between 3 and 5 years of age, multiple logistic regression analyses were applied. Further, in prenatally stressed adult offspring of BALB/c-mated BALB/c female mice, asthma was experimentally induced by ovalbumin (OVA) sensitization. In addition to the prenatal stress challenge, some pregnant females were treated with the progesterone derivative dihydrodydrogesterone (DHD). In humans, we observed that high levels of maternal progesterone in early human pregnancies were associated with a decreased risk for an allergic airway disease (asthma or allergic rhinitis) in daughters (adjusted OR 0.92; 95% confidence interval [CI] 0.84 to 1.00) but not sons (aOR 1.02, 95% CI 0.94-1.10). In mice, prenatal DHD supplementation of stress-challenged dams attenuated prenatal stress-induced airway hyperresponsiveness exclusively in female offspring. Reduced levels of maternal progesterone during pregnancy-which can result from high stress perception-increase the risk for allergic airway diseases in females but not in males. Key messages: Lower maternal progesterone during pregnancy increases the risk for allergic airway disease

  6. Estrogen and progesterone receptor testing in breast carcinoma: concordance of results between local and reference laboratories in Brazil

    Directory of Open Access Journals (Sweden)

    Sheila Cristina Lordelo Wludarski

    Full Text Available CONTEXT AND OBJECTIVE: Breast cancer accounts for approximately one quarter of all cancers in females. Estrogen and progesterone receptor testing has become an essential part of the clinical evaluation of breast carcinoma patients, and accurate results are critical in identifying patients who may benefit from hormone therapy. The present study had the aim of investigating the concordance of the results from hormone receptor tests between a reference laboratory and local (or community laboratories in Brazil. DESIGN AND SETTING: Retrospective study at a reference pathology laboratory. METHODS: The concordance in the results from hormone receptor tests between a reference laboratory and 146 local laboratories in Brazil was compared in relation to 500 invasive breast carcinoma cases, using immunohistochemistry. RESULTS: There was concordance in 89.4% (447/500 cases and 85.0% (425/500 cases of the results from estrogen (κ = 0.744, P < 0.001 and progesterone (κ = 0.688, P < 0.001 receptor tests, respectively, between local and reference laboratories. This was similar to findings in other countries. The false negative rates from estrogen and progesterone receptor tests in local laboratories were 8.7% and 14.4%, respectively. The false positive rates from estrogen and progesterone receptor tests in local laboratories were 15.5% and 16.0%, respectively. CONCLUSION: Technical and result interpretation issues may explain most of the discordances in hormone receptor testing in local laboratories. Validation of estrogen and progesterone receptor tests at local laboratories, with rigorous quality control measures, is strongly recommended in order to avoid erroneous treatment of breast cancer patients.

  7. Effect of 2 corpora lutea on blood perfusion, peripheral progesterone, and hepatic steroid-inactivating enzymes in dairy cattle.

    Science.gov (United States)

    Voelz, B E; Cline, G F; Hart, C G; Lemley, C O; Larson, J E

    2015-01-01

    The luteal structure that develops postovulation is critical to the facilitation and maintenance of pregnancy in dairy cattle. The objectives of this experiment were to determine if the induction of an accessory corpus luteum (CL), via human chorionic gonadotropin, altered blood perfusion of CL, peripheral concentrations of progesterone, or hepatic steroid-inactivating enzymes. Twenty-eight late-lactation Holstein cows were synchronized using the Ovsynch protocol and randomly assigned to 1 of 2 treatment groups. Cows received either an injection of human chorionic gonadotropin (1,000IU, i.m.) to induce an accessory CL (cows had exactly 2CL in 1 ovary) or no treatment (cows had exactly 1CL). Corpora lutea were examined daily from d 10 to 18 (d 0 was induced ovulation) via Doppler ultrasonography and a blood sample was collected. Volume of the CL was recorded, as well as images and videos of each CL, which were analyzed for blood perfusion. On d 13, a liver biopsy was performed to analyze hepatic steroid-inactivating enzymes. Cows with 1 or 2CL had similar peripheral concentrations of progesterone. Cows with 2CL had similar luteal volumes to cows with 1CL but cows with 2CL had greater total luteal blood perfusion. Hepatic enzyme [cytochrome P450 (CYP) 1A, 3A, and 2C, aldo-keto reductase 1C, and uridine diphosphate glucuronosyltransferase] activities did not differ between cows with 1 and 2CL. Overall, the observed increase in total luteal blood perfusion in cows with 2CL did not correspond to differences in peripheral concentrations of progesterone or clearance of progesterone measured by the hepatic enzyme activity. This could indicate that induction of an accessory CL would not affect concentrations of progesterone necessary to maintain pregnancy. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  8. Estradiol augments while progesterone inhibits arginine transport in human endothelial cells through modulation of cationic amino acid transporter-1.

    Science.gov (United States)

    Bentur, Ohad S; Schwartz, Doron; Chernichovski, Tamara; Ingbir, Merav; Weinstein, Talia; Chernin, Gil; Schwartz, Idit F

    2015-08-15

    Decreased generation of nitric oxide (NO) by endothelial NO synthase (eNOS) characterizes endothelial dysfunction (ECD). Delivery of arginine to eNOS by cationic amino acid transporter-1 (CAT-1) was shown to modulate eNOS activity. We found in female rats, but not in males, that CAT-1 activity is preserved with age and in chronic renal failure, two experimental models of ECD. In contrast, during pregnancy CAT-1 is inhibited. We hypothesize that female sex hormones regulate arginine transport. Arginine uptake in human umbilical vein endothelial cells (HUVEC) was determined following incubation with either 17β-estradiol (E2) or progesterone. Exposure to E2 (50 and 100 nM) for 30 min resulted in a significant increase in arginine transport and reduction in phosphorylated CAT-1 (the inactive form) protein content. This was coupled with a decrease in phosphorylated MAPK/extracellular signal-regulated kinase (ERK) 1/2. Progesterone (1 and 100 pM for 30 min) attenuated arginine uptake and increased phosphorylated CAT-1, phosphorylated protein kinase Cα (PKCα), and phosphorylated ERK1/2 protein content. GO-6976 (PKCα inhibitor) prevented the progesterone-induced decrease in arginine transport. Coincubation with both progesterone and estrogen for 30 min resulted in attenuated arginine transport. While estradiol increases arginine transport and CAT-1 activity through modulation of constitutive signaling transduction pathways involving ERK, progesterone inhibits arginine transport and CAT-1 via both PKCα and ERK1/2 phosphorylation, an effect that predominates over estradiol. Copyright © 2015 the American Physiological Society.

  9. Preterm birth prevention in twin pregnancies with progesterone, pessary, or cerclage: a systematic review and meta-analysis.

    Science.gov (United States)

    Jarde, A; Lutsiv, O; Park, C K; Barrett, J; Beyene, J; Saito, S; Dodd, J M; Shah, P S; Cook, J L; Biringer, A B; Giglia, L; Han, Z; Staub, K; Mundle, W; Vera, C; Sabatino, L; Liyanage, S K; McDonald, S D

    2017-07-01

    About half of twin pregnancies deliver preterm, and it is unclear whether any intervention reduces this risk. To assess the evidence for the effectiveness of progesterone, cerclage, and pessary in twin pregnancies. We searched Medline, EMBASE, CINAHL, Cochrane Central Register of Controlled Trials, and ISI Web of Science, without language restrictions, up to 25 January 2016. Randomised controlled trials of progesterone, cerclage, or pessary for preventing preterm birth in women with twin pregnancies, without symptoms of threatened preterm labour. Two independent reviewers extracted data using a piloted form. Study quality was appraised with the Cochrane Risk of Bias tool. We performed pairwise inverse variance random-effects meta-analyses. We included 23 trials (all but three were considered to have a low risk of bias) comprising 6626 women with twin pregnancies. None of the interventions significantly reduced the risk of preterm birth overall at <34 or <37 weeks of gestation, or neonatal death, our primary outcomes, compared to a control group. In women receiving vaginal progesterone, the relative risk (RR) of preterm birth <34 weeks of gestation was 0.82 (95% CI 0.64-1.05, seven studies, I(2)  36%), with a significant reduction in some key secondary outcomes, including very low birthweight (<1500 g, RR 0.71, 95% CI 0.52-0.98, four studies, I(2)  46%) and mechanical ventilation (RR 0.61, 95% CI 0.45-0.82, four studies, I(2)  22%). In twin gestations, although no overarching intervention was beneficial for the prevention of preterm birth and its sequelae, vaginal progesterone improved some important secondary outcomes. Vaginal progesterone may be beneficial in twin pregnancies, but not 17-OHPC, cerclage, or pessary. © 2017 Royal College of Obstetricians and Gynaecologists.

  10. Potential contribution of progesterone receptors to the development of sexual behavior in male and female mice.

    Science.gov (United States)

    Desroziers, Elodie; Brock, Olivier; Bakker, Julie

    2017-04-01

    We previously showed that estradiol can have both defeminizing and feminizing effects on the developing mouse brain. Pre- and early postnatal estradiol defeminized the ability to show lordosis in adulthood, whereas prepubertal estradiol feminized this ability. Furthermore, we found that estradiol upregulates progesterone receptors (PR) during development, inducing both a male-and female-typical pattern of PR expression in the mouse hypothalamus. In the present study, we took advantage of a newly developed PR antagonist (ZK 137316) to determine whether PR contributes to either male- or female-typical sexual differentiation. Thus groups of male and female C57Bl/6j mice were treated with ZK 137316 or OIL as control: males were treated neonatally (P0-P10), during the critical period for male sexual differentiation, and females were treated prepubertally (P15-P25), during the critical period for female sexual differentiation. In adulthood, mice were tested for sexual behavior. In males, some minor effects of neonatal ZK treatment on sexual behavior were observed: latencies to the first mount, intromission and ejaculation were decreased in neonatally ZK treated males; however, this effect disappeared by the second mating test. By contrast, female mice treated with ZK during the prepubertal period showed significantly less lordosis than OIL-treated females. Mate preferences were not affected in either males or females treated with ZK during development. Taken together, these results suggest a role for PR and thus perhaps progesterone in the development of lordosis behavior in female mice. By contrast, no obvious role for PR can be discerned in the development of male sexual behavior. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Magnetically responsive polycaprolactone nanoparticles for progesterone screening in biological and environmental samples using gas chromatography.

    Science.gov (United States)

    Es'haghi, Zarrin; Nezhadali, Azizollah; Khatibi, Aram-Dokht

    2016-08-01

    A new Fe3O4/poly(є-caprolactone) (PCL) magnetite nanocomposite was fabricated and used as a sorbent for magnetically mediated PCL microspheres solid-phase extraction (MM-PCL-SPE) followed by gas chromatography-flame ionization detection (GC-FID) for monitoring of progesterone (PGN) hormone in biological and environmental matrices, namely blood serum, tap water, urine, and hospital wastewater. The nanomagnetite core of the sorbent was synthesized by a co-precipitation method. Magnetic nanoparticles (MNPs) were then microencapsulated with PCL microspheres using emulsion polymerization. The nanocomposite was characterized by scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR). The magnetite sorbent can be effectively dispersed in aqueous solution and attracted to an external magnetic field. The MM-PCL-SPE process for PGN assay involved (a) dispersion of the sorbent in the donor phase aqueous solution with sonication, (b) exposure to a magnetic field to collect sorbent that had adsorbed the analyte, and (c) solvent desorption of extracted PGN for GC-FID analysis. The work demonstrates the usefulness of MM-PCL-SPE in the rapid and sensitive monitoring of trace amounts of PGN in real samples. The limit of detection (LOD) and limit of quantification (LOQ) were 1.00 and 3.30 ng/mL, respectively. The relative recoveries in real samples were adequate. Linearity was observed over a wide range of 2.2-10,000.0 ng/mL in aqueous media and urine and 0.01-70.0 μg/mL in blood serum. Graphical Abstract In this research new Fe3O4/poly(є-caprolactone) (PCL) magnetite microspheres were developed as an efficient sorbent for solid-phase extraction of progesterone hormone in biological and environmental matrices.

  12. Coordinated Regulation Among Progesterone, Prostaglandins, and EGF-Like Factors in Human Ovulatory Follicles.

    Science.gov (United States)

    Choi, Yohan; Wilson, Kalin; Hannon, Patrick R; Rosewell, Katherine L; Brännström, Mats; Akin, James W; Curry, Thomas E; Jo, Misung

    2017-06-01

    In animal models, the luteinizing hormone surge increases progesterone (P4) and progesterone receptor (PGR), prostaglandins (PTGs), and epidermal growth factor (EGF)-like factors that play essential roles in ovulation. However, little is known about the expression, regulation, and function of these key ovulatory mediators in humans. To determine when and how these key ovulatory mediators are induced after the luteinizing hormone surge in human ovaries. Timed periovulatory follicles were obtained from cycling women. Granulosa/lutein cells were collected from in vitro fertilization patients. The in vivo and in vitro expression of PGR, PTG synthases and transporters, and EGF-like factors were examined at the level of messenger RNA and protein. PGR binding to specific genes was assessed. P4 and PTGs in conditioned media were measured. PGR, PTGS2, and AREG expressions dramatically increased in ovulatory follicles at 12 to 18 hours after human chorionic gonadotropin (hCG). In human granulosa/lutein cell cultures, hCG increased P4 and PTG production and the expression of PGR, specific PTG synthases and transporters, and EGF-like factors, mimicking in vivo expression patterns. Inhibitors for P4/PGR and EGF-signaling pathways reduced hCG-induced increases in PTG production and the expression of EGF-like factors. PGR bound to the PTGS2, PTGES, and SLCO2A1 genes. This report demonstrated the time-dependent induction of PGR, AREG, and PTGS2 in human periovulatory follicles. In vitro studies indicated that collaborative actions of P4/PGR and EGF signaling are required for hCG-induced increases in PTG production and potentiation of EGF signaling in human periovulatory granulosa cells.

  13. Medroxyprogesterone acetate or long-acting progesterone in the biostimulation of lambs

    Directory of Open Access Journals (Sweden)

    Luis C.O. Magalhães

    2010-09-01

    Full Text Available The aim of this study was to evaluate the response of prepubertal ewe lambs to exogenous administration of either medroxyprogesterone acetate (MAP or long-acting progesterone (LAP together with biostimulation. Two Pool Dorset adult males and 75 mixed-breed prepubertal ewe lambs (average of 179 days-old and 30.0kg were used. The females were randomly assigned to three different groups. In the first group the females were submitted to the insertion of intravaginal sponges containing MAP (60 mg for 12 days and were then biostimulated for eight weeks. In the second group the females were submitted to a single injection of LAP (225 mg and then to biostimulation for eight weeks. In the last group, the females were only submitted to biostimulation for eight weeks. Animals were considered cyclic when plasma progesterone (P4 concentration exceeded 1.0 ng/mL in at least one of two consecutive blood samples taken within a 7-day interval in three distinct experimental moments. After treatments 93.3% of the females disregarding their group started their cyclicity and most of them (92.0%, continued to be cyclic after 63 days of either MAP or LAP together with biostimulation under both male and female effect. We conclude that prepubertal ewe lambs when submitted to protocols of either MAP or LAP followed by biostimulation result in puberty at the 7 month of age. It can be deducted that some ewe lambs submitted to the administration of either MAP or LAP together with biostimulation promoted a multiplier effect upon the other young females that were then stimulated to start cyclicity.

  14. Inhibition of peripubertal sheep mammary gland development by cysteamine through reducing progesterone and growth factor production.

    Science.gov (United States)

    Zhao, Yong; Feng, Yanni; Zhang, Hongfu; Kou, Xin; Li, Lan; Liu, Xinqi; Zhang, Pengfei; Cui, Liantao; Chu, Meiqiang; Shen, Wei; Min, Lingjiang

    2017-02-01

    Cysteamine has been used for treating cystinosis for many years, and furthermore it has also been used as a therapeutic agent for different diseases including Huntington's disease, Parkinson's disease (PD), nonalcoholic fatty liver disease, malaria, cancer, and others. Although cysteamine has many potential applications, its use may also be problematic. The effects of low doses of cysteamine on the reproductive system, especially the mammary glands are currently unknown. In the current investigation, low dose (10 mg/kg BW/day) of cysteamine did not affect sheep body weight gain or organ index of the liver, spleen, or heart; it did, however, increase the levels of blood lymphocytes, monocytes, and platelets. Most interestingly, it inhibited mammary gland development after 2 or 5 months of treatment by reducing the organ index and the number of mammary gland ducts. Plasma growth hormone and estradiol remained unchanged; however, plasma progesterone levels and the protein level of HSD3β1 in sheep ovaries were decreased by cysteamine. In addition to steroid hormones, growth factors produced in the mammary glands also play crucial roles in mammary gland development. Results showed that protein levels of HGF, GHR, and IGF1R were decreased after 5 months of cysteamine treatment. These findings together suggest that progesterone and local growth factors in mammary glands might be involved in cysteamine initiated inhibition of pubertal ovine mammary gland development. Furthermore, it may lead to a reduction in fertility. Therefore, cysteamine should be used with great caution until its actions have been further investigated and its limitations overcome. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Intravaginal progesterone insert to synchronize return to estrus of previously inseminated dairy cows.

    Science.gov (United States)

    Chenault, J R; Boucher, J F; Dame, K J; Meyer, J A; Wood-Follis, S L

    2003-06-01

    An intravaginal progesterone insert (CIDR insert; 1.38 g of progesterone) was evaluated for synchronization of returns to estrus (SR), conception rate (CR), and pregnancy rate (PR) in dairy cows previously artificially inseminated (AI). Healthy, nonpregnant, lactating Holstein cows, > or = 40 and returns to estrus from 18 to 26 +/- 1 d after initial AI (resynchrony period) and were reinseminated if in estrus. Vaginal mucus on CIDR inserts (97.3% retention) at removal was scored: 1 = no mucus; 2 = clear; 3 = cloudy; 4 = yellow; and 5 = red or brown. Percentage of cows in estrus (SR) during the 3 d after CIDR insert removal was contrasted to the highest 3-d cumulative percentage in estrus for controls. Cows conceiving to initial AI were omitted in calculations of SR, CR, and PR during resynchrony. Mucous scores of 3 or 4 (mild irritation) were observed in 65% of cows and a score of 5 (more severe irritation) was observed in 2%; otherwise, health was unaffected. The PR to initial AI was lower for cows subsequently receiving CIDR inserts than for controls (32.7 vs. 36.7%). The CIDR insert increased SR (34.1 vs. 19.3% in 3 d) and overall estrus detection (43% in 4 d vs. 36% in 9 d) compared with controls. For the 9-d resynchrony period, CR and PR for CIDR-treated (26.7, 12.2%) and control (30.9, 11.1%) cows did not differ significantly. The CIDR inserts improved synchrony of returns to estrus, slightly reduced PR to initial AI, but did not affect CR or PR to AI during the resynchrony period.

  16. Nonclassical Mechanisms of Progesterone Action in the Brain: II. Role of Calmodulin-Dependent Protein Kinase II in Progesterone-Mediated Signaling in the Hypothalamus of Female Rats

    Science.gov (United States)

    Balasubramanian, Bhuvana; Portillo, Wendy; Reyna, Andrea; Chen, Jian Zhong; Moore, Anthony N.; Dash, Pramod K.; Mani, Shaila K.

    2008-01-01

    In addition to the activation of classical progestin receptor-dependent genomic pathway, progesterone (P) can activate nonclassical, membrane-initiated signaling pathways in the brain. We recently demonstrated rapid P activation of second-messenger kinases, protein kinase A, and protein kinase C in the ventromedial nucleus (VMN) and preoptic area (POA) of rat brain. To determine whether P can activate yet another Ca+2dependent kinase, we examined the rapid P modulation of calcium and calmodulin-dependent protein kinase II (CaMKII) in the VMN and POA in female rats. A rapid P-initiated activation of CaMKII basal activity was observed in the VMN but not the POA at 30 min. Estradiol benzoate (EB) priming enhanced this CaMKII basal activity in both the VMN and POA. CaMKII protein levels and phosphorylation of Thr-286 moiety on CaMKII, however, remained unchanged with EB and/or P treatments, suggesting that the changes in the CaMKII kinase activity are due to rapid P modulation of the kinase activity and not its synthesis or autoactivation. Furthermore, intracerebroventricular (icv) administration of a CaMKII-specific inhibitor, KN-93, 30 min prior to the P infusion, in EB-primed, ovariectomized female rats inhibited CaMKII activation but not protein kinase A and protein kinase C activities. Interestingly, icv administration of KN-93 30 min prior to P infusion (icv) resulted in a reduction but not total inhibition of P-facilitated lordosis response in EB-primed female rats. These observations suggest a redundancy or, alternately, a hierarchy in the P-regulated activation of kinase signaling cascades in female reproductive behavior. PMID:18617607

  17. TGF-β1 downregulates StAR expression and decreases progesterone production through Smad3 and ERK1/2 signaling pathways in human granulosa cells.

    Science.gov (United States)

    Fang, Lanlan; Chang, Hsun-Ming; Cheng, Jung-Chien; Leung, Peter C K; Sun, Ying-Pu

    2014-11-01

    Regulation of progesterone production in granulosa cells is important for normal reproductive functions. Steroidogenic acute regulatory protein (StAR) is recognized as the key regulatory protein involved in the rate-limiting step of steroidogenesis. TGF-β1 protein is detected in human follicular fluid, and TGF-β1 and its receptors are expressed in human granulosa cells. However, the functional role of TGF-β1 in the regulation of StAR expression and progesterone production in human granulosa cells remains unknown. Our objective was to investigate the effects of TGF-β1 on StAR expression and progesterone production in human granulosa cells. SVOG cells are human granulosa cells that were obtained from women undergoing in vitro fertilization and immortalized with SV40 large T antigen. SVOG cells were used to investigate the effects of TGF-β1 on StAR expression and progesterone production at an academic research center. Levels of mRNA and protein were examined by RT-qPCR and western blotting, respectively. The accumulation levels of progesterone were measured by enzyme-linked immunosorbent assay (ELISA). TGF-β1 treatment downregulated StAR expression and decreased progesterone production. The suppressive effects of TGF-β1 on StAR expression and progesterone production were abolished by the inhibition of TGF-β type I receptor. In addition, treatment with TGF-β1 activated the Smad2/3 and ERK1/2 signaling pathways. The inhibition of the Smad3 and ERK1/2 signaling pathways attenuated the TGF-β1-induced downregulation of StAR expression and progesterone production. TGF-β1 downregulated StAR expression and decreased progesterone production by activating the Smad3 and ERK1/2 signaling pathways in human granulosa cells.

  18. In vivo induction of oocyte maturation and ovulation in zebrafish.

    Directory of Open Access Journals (Sweden)

    Toshinobu Tokumoto

    Full Text Available The maturation of fish oocytes is a well-characterized system induced by progestins via non-genomic actions. In a previous study, we demonstrated that diethylstilbestrol (DES, a non-steroidal estrogen, induces fish oocyte maturation via the membrane progestin receptor (mPR. Here, we attempted to evaluate the effect of DES as an environmental endocrine disrupting chemical (EDC upon fish oocyte maturation using live zebrafish. DES triggered oocyte maturation within several hours in vivo when administrated directly into the surrounding water. The natural teleost maturation-inducing hormone, 17alpha, 20beta-dihydroxy-4-pregnen-3-one (17,20beta-DHP also induced oocyte maturation in vivo. Steroids such as testosterone, progesterone or 17alpha-hydroxyprogesterone were also effective in vivo. Further studies indicated that externally applied 17,20beta-DHP even induced ovulation. In contrast to 17,20beta -DHP, DES induced maturation but not ovulation. Theoretically this assay system provides a means to distinguish pathways involved in the induction of ovulation, which are known to be induced by genomic actions from the pathway normally involved in the induction of oocyte maturation, a typical non-genomic action-dependent pathway. In summary, we have demonstrated the effect of EDCs on fish oocyte maturation in vivo. To address the effects, we have explored a conceptually new approach to distinguish between the genomic and non-genomic actions induced by steroids. The assay can be applied to screens of progestin-like effects upon oocyte maturation and ovulation for small molecules of pharmacological agents or EDCs.

  19. Hiperplasia adrenal congênita: dosagem da 17-hidroxiprogesterona basal para seleção e casos para realização do teste de estímulo com ACTH sintético Congenital adrenal hyperplasia: measurement of basal 17-hydroxyprogesterone as a screening test to select patients for the synthetic ACTH provocative test

    Directory of Open Access Journals (Sweden)

    Lúcia Helena Coelho Nóbrega

    2004-05-01

    deficiency. Clinical presentation varies from life-threatening salt-losing adrenal hyperplasia to simple androgenic states, which can be of late-onset and very similar to polycystic ovary syndrome. Diagnosis is usually made by synthetic ACTH provocative tests but efforts are being made to simplify this investigation. OBJECTIVE: to evaluate basal 17-hydroxyprogesterone as a predictor of the provocative test for the diagnosis of late-onset congenial adrenal hyperplasia. METHODS: A total of 122 patients under clinical suspicion of diagnosis of late-onset congenial adrenal hyperplasia were included and retrospectively evaluated in the study. Such suspicion included signs and/or symptoms of hyperandrogenism (hirsutism, acne, oily skin, menstrual irregularity etc.. All the patients were submitted to the 0.25mg synthetic ACTH provocative test (Synacthen®. After resting for 60 minutes, the samples were taken in the basal time and 60 minutes after the administration of 0.25mg synthetic ACTH, in order to assay 17-hydroxiprogesteron, the venous access being kept through a heparinized catheter. Radioimmuoessay was the method used to accomplish the assay of seric 17-hydroxiprogesteron. The sensitivity and specificity of the basal 17-hydroxiprogesteron were measured, assessing several cutoff points. ROC curves were made to analyze the test performance, using the software Medcalc®. RESULTS: ROC curve analysis showed that the best cutoff point was 181 ng/dl, which was very similar to the most common recommendation of 200 ng/dl of the literature. The cutoff point of 200 ng/dl shows positive and negative predictive values of 75 and 100%, and accuracy of 98,4% as a diagnostic test for late-onset adrenal hyperplasia. CONCLUSIONS: considering our data, we suggest that all hyperandrogenic patients should start the investigation with basal 17-hydroxyprogesteron and in case it is above 181 ng/dl, then they should do the synthetic 17-hydroxyprogesteron provocative test.

  20. Summary, the 20th quality control survey for radioisotopes in vitro tests in Japan, 1998

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1999-11-01

    For advancement of radioisotope in vitro tests such as radioimmunoassay and immunoradiometric assay, the Subcommittee for Radioisotope in vitro Test in Medical and Pharmaceutical Committee of Japan Radioisotope Association has conducted the yearly quality control survey for the test facilities in Japan since 1978. This is the summary of the 20th survey in 1998 where non-radioisotope tests like enzyme-immunoassay were involved as well. The survey was done for 143 facilities: 20 national and public university hospitals, 18 private university hospitals, 8 national hospitals, 13 public hospitals, 21 private hospitals, 41 hygienic laboratories and 22 manufacturers of reagents. Facilities examined intra- and between day-reproducibility, freeze-thaw effect and time change of the measured values on the same samples. Assays were for: growth hormone (h), somatomedin C, follicle stimulating h, luteinizing h, prolactin, thyroid stimulating h, triiodothyronines, thyroxines, thyroxine binding protein, calcitonin, insulin, C-peptide, glucagons, gastrin, testosterones, estradiol, progesterone, gonadotropin, 17{alpha}-hydroxyprogesterone, aldosterone, cortisol, dehydroepiandorosterone sulfate, renin, IgE, digoxin, {alpha}-fetoprotein, carcinoembryonic antigen, tissue polypeptide antigen, CA (125, 19-9 and 15-3), prostatic acid phosphatase, prostate specific antigen, {beta}2-microglobulin, ferritin, and neuron specific enolase. There was no great difference between this and last survey results although tendency of improvement was recognized. There were problems to be solved from the standpoint of clinical practice. (K.H.)

  1. In vitro fertilization as a diagnostic and therapeutic tool in a patient with partial 17,20-desmolase deficiency.

    Science.gov (United States)

    Pellicer, A; Miró, F; Sampaio, M; Gómez, E; Bonilla-Musoles, F M

    1991-05-01

    To present a case with 17,20-desmolase activity deficiency in which in vitro fertilization (IVF) served not only as a therapeutic approach but also as a diagnostic tool for the specificity of the enzymatic deficiency. IVF in the patient under study compared with a control group. All women treated with pure follicle-stimulating hormone (FSH). IVF program at the Instituto Valenciano de Infertilidad. A patient with primary amenorrhea, who was the subject under study, and seven normally cycling control patients undergoing IVF in the same series. IVF, steroidogenesis in vitro of granulosa-luteal cell obtained at ovum pick-up. Oocyte fertilization and embryo cleavage. Serum and follicular fluid (FF) levels of estradiol (E2), progesterone (P), testosterone (T), androstendione (A), 17 alpha-hydroxyprogesterone (17-OHP). In vitro accumulation of E2 and P. Ovulation induction with FSH was successful in achieving follicular development despite low circulating E2. Fertilization and cleavage rates were similar to the control subjects. The patient developed ovarian hyperstimulation. The lack of 17,20-desmolase activity was detected by normal P levels in serum and FF, high 17-OHP, and low T, A, and E2 levels in serum and FF. Granulosaluteal cell cultures in the presence of T restored normal E2 and P production in response to gonadotropins. In patients with 17,20-desmolase deficiency, follicular development, oocyte maturation, and fertilization can take place in a low estrogenic environment.

  2. Summary. The 19th quality control survey for radioisotope in vitro tests in Japan, 1997

    Energy Technology Data Exchange (ETDEWEB)

    Shishiba, Yoshimasa; Shimizu, Taeko [Toranomon Hospital, Tokyo (Japan); Ichihara, Kiyoshi; Kousaka, Tadako; Kobayashi, Hisae; Tsushima, Toshio; Hoshino, Minoru; Mori, Mikio

    1998-11-01

    This summary concerns results of the survey in the title performed by the Subcommittee for Radioisotope in vitro Test in the Medical and Pharmaceutical Committee, Japan Radioisotope Association. The survey was conducted in 161 facilities in Japan including public and private hospitals, health institutes and reagent manufacturers. Samples were sent to the facilities and subjected to examinations of intra- and inter-day reproducibility, freeze-thawing effects and periodical changes of the measured values. Methods employed were RIA, IRMA, EIA, ELISA, LPIA, PAMIA, FIA, FPIA, NIA, LAT, CLIA and ECLIA. Results were analyzed by variation coefficients in the kit and between the kits. Samples were for: growth hormone, somatomedin C, follicle stimulating hormone, luteinizing hormone, prolactin, thyroid stimulating hormone, triiodothyronine, thyroxine, thyroxine binding globulin, calcitonin, insulin, C-peptide, glucagon, gastrin, testosterone, estradiol, progesterone, {beta}human chorionic gonadotropin, 17{alpha}-hydroxyprogesterone, aldosterone, cortisol, dehydroepiandrosterone, renin, immunogloblin E, digoxin, {alpha}-fetoprotein, carcinoembryonic antigen, tissue polypeptide antigen, CA125, CA19-9, CA15-3, prostatic acid phosphatase, prostate specific antigen, {beta}{sub 2}-microgloblin and ferritin. Results were found rather unsatistactory for some products in the clinical practice, necessary for improvement of detection for some tests and needed for some kits for solving the problems of difference between kits and of matrix effect. (K.H)

  3. Daily low-dose hCG stimulation during the luteal phase combined with GnRHa triggered IVF cycles without exogenous progesterone

    DEFF Research Database (Denmark)

    Andersen, Claus Yding; Elbaek, Helle Olesen; Alsbjerg, Birgit

    2015-01-01

    with exogenous progesterone. WHAT IS KNOWN ALREADY: A bolus of hCG for final maturation of follicles in connection with COS may induce the risk of OHSS and the luteal phase progesterone levels rise very abruptly in the early luteal phase. STUDY DESIGN, SIZE, DURATION: This is a proof-of-concept study conducted...... antagonist protocol. Two study arms were included both having 125 IU hCG daily for luteal phase support without exogenous progesterone after using a GnRHa trigger for ovulation induction. In both study arms exogenous FSH was stopped on stimulation day 6 and replaced by exogenous hCG that was initiated...

  4. Photoacoustic methods for in vitro study of kinetics progesterone release from the biodegradation of polyhydroxybutyrate/polycaprolactone used as intravaginal devices

    Energy Technology Data Exchange (ETDEWEB)

    Souza Filho, N. E. [Universidade Estadual de Maringá, Departamento de Física, Grupo de Estudos dos Fenômenos Fototérmicos-GEFF/DFI/UEM, Av. Colombo 5790, Maringá-PR (Brazil); Universidade Federal de Santa Maria, Departamento de Eng. Acústica, Av. Roraima 1000, CEP 97105–900, Santa Maria-RS (Brazil); Mariucci, V. V. G.; Dias, G. S.; Szpak, W.; Medina, A. N.; Baesso, M. L.; Bento, A. C. [Universidade Estadual de Maringá, Departamento de Física, Grupo de Estudos dos Fenômenos Fototérmicos-GEFF/DFI/UEM, Av. Colombo 5790, Maringá-PR (Brazil); Miguez, P. H. P.; Madureira, E. H. [Universidade de São Paulo, Departamento de Reprodução Animal–VRA/USP, Av. Prof. Dr. Orlando Marques Paiva 87, São Paulo–SP (Brazil)

    2013-09-30

    Intravaginal devices composed of polyhydroxybutyrate/polycaprolactone blends incorporating progesterone were used over eight days in crossbred cow ovariectomized, and then analyzed with photoacoustic methods, measuring the absorption spectra, thermal diffusivity, and inspecting its degradation by means of scanning electron microscopy. The characteristic time found for progesterone release was TR ∼ 53 h, and the typical time found for biodegradation was TB ∼ 30 h. Morphological analysis complements the study showing that release of progesterone and biodegradation of the blend occurs on sample surface.

  5. A randomized placebo-controlled trial of progesterone with or without hypothermia in patients with acute severe traumatic brain injury.

    Science.gov (United States)

    Sinha, Sumit; Raheja, Amol; Samson, Neha; Goyal, Keshav; Bhoi, Sanjeev; Selvi, Arul; Sharma, Pushpa; Sharma, Bhawani Shankar

    2017-01-01

    Among newer neuroprotectant modalities, hypothermia and progesterone have shown a beneficial role in preliminary studies enrolling patients with severe traumatic brain injury (sTBI). The primary objective of this study was to evaluate the efficacy of progesterone with or without prophylactic hypothermia in acute sTBI patients. This is a prospective, outcome assessor, statistician blinded, randomized, and placebo-controlled phase II trial of progesterone with or without hypothermia (factorial design). All adult patients (18-65 years) with acute sTBI (Glasgow coma score of 4-8) and presenting to trauma center within 8 h after injury were included in the trial. Computer-generated randomization was done after exclusion; sequentially numbered, opaque, sealed envelope technique was used for allocation concealment. The enrollment duration was from January 2012 to October 2014. The primary endpoint was dichotomized Glasgow outcome score (GOS) [poor recovery = GOS 1-3; good recovery = GOS 4-5], and secondary endpoints were functional independence measure (FIM) score and mortality rate at 6 and 12 months follow-up after recruitment. A total of 107 patients were randomized into four groups (placebo [n = 27], progesterone [n = 26], hypothermia alone [n = 27], and progesterone + hypothermia [n = 27]). The study groups were comparable in baseline parameters except for a higher incidence of decompressive craniectomy in the placebo group (P = 0.001). The analysis of GOS at 6 months revealed statistically significant better outcome in the hypothermia group (82%; P = 0.01) and a weaker evidence for progesterone group (74%; P = 0.07) as compared with the placebo group (44%). However, the outcome benefit was marginal at 1-year follow-up for the hypothermia group (82% vs. 58%, P = 0.17). The adjusted odds ratio of poor recovery at 6 months in the hypothermia group was 0.21 (confidence interval = 0.05-0.84, P = 0.03), as compared with the placebo group. Although mean FIM scores at 6 and

  6. Effects of different supplemental soya bean oil levels on the performance of prepubertal Saanen goats: Oestrogen and progesterone release.

    Science.gov (United States)

    Bomfim, G F; Merighe, G K F; de Oliveira, S A; Rodrigues, A D; Augusto, L; Teixeira, I A M A; de Resende, K T; Negrao, J A

    2016-12-01

    The aim of this study was to investigate the effects of different levels of soya bean oil in the total diet on the growth rate, metabolic changes, and oestrogen and progesterone release in Saanen goats. After dietary adaptation, 21 prepubertal goats (weight of 29.12 ± 0.91 kg, 230 days old) were randomly distributed among three diets of D2: inclusion of 2% soya bean oil in the total diet; D3: basal diet - inclusion of 3% soya bean oil in the total diet; and D4: inclusion of 4% soya bean oil in the total diet. The basal diet (D3) was formulated to promote a daily gain of 0.140 kg. The goats were weighed, and their blood samples were collected weekly. Glucose, cholesterol, triglycerides, total protein, urea, non-esterified fatty acids, beta-hydroxybutyrate, oestrogen and progesterone in the plasma were measured. Prepubertal goats that were fed D4 exhibited a significantly lower dry matter intake, urea and cholesterol levels compared with the goats that were fed D2 and D3. Indeed, goats that were fed D4 displayed a significantly lower final weight than goats that were fed D2 and D3. In contrast, the inclusion of soya bean oil in the diet increased the progesterone and oestrogen concentrations, and goats that were fed D4 released a significantly higher concentration of progesterone than those that were fed D2 and D3. Furthermore, the percentage of goats with a progesterone level greater than 1 ng/ml (functional Corpus luteum) was significantly higher among the goats that were fed D3 and D4 than among those that were fed D2. In this study, although the inclusion of 4% soya bean oil in the diet decreased dry matter intake and growth rate, it increased progesterone concentration and the percentage of goats with a functional Corpus luteum, suggesting that the inclusion of soya bean oil accelerated puberty in prepubertal goats. Journal of Animal Physiology and Animal Nutrition © 2016 Blackwell Verlag GmbH.

  7. Progesterone-induced changes in the phosphoryl potential during the meiotic divisions in amphibian oocytes: Role of Na/K-ATPase

    National Research Council Canada - National Science Library

    Gene A Morrill; Terry L Dowd; Adele B Kostellow; Raj K Gupta

    2011-01-01

      Abstract Background: Progesterone triggers resumption of the first meiotic division in the Rana pipiens oocyte by binding to the N-terminal external loop of the catalytic subunit of Na/K-ATPase, releasing a cascade...

  8. Progesterone receptor isoform analysis by quantitative real-time polymerase chain reaction in formalin-fixed, paraffin-embedded canine mammary dysplasias and tumors

    DEFF Research Database (Denmark)

    Guil-Luna, S.; Stenvang, Jan; Brünner, Nils

    2014-01-01

    Cloning and sequencing of the progesterone receptor gene in dogs have revealed 2 isoforms, A and B, transcribed from a single gene. Distribution of isoforms A and B in canine mammary lesions has hitherto been investigated only by Western blot analysis. This study analyzed progesterone receptor...... and its isoforms in formalin-fixed, paraffin-embedded tissue samples from canine mammary lesions (4 dysplasias, 10 benign tumors, and 46 carcinomas) using 1-step SYBR Green quantitative real-time polymerase chain reaction (RT-qPCR). Progesterone receptor was expressed in 75% of dysplasias, all benign...... of the canine mammary gland. These findings will facilitate future research into the role of progesterone receptor isoforms in the progression of canine mammary tumors....

  9. Progesterone binding nano-carriers based on hydrophobically modified hyperbranched polyglycerols

    Science.gov (United States)

    Alizadeh Noghani, M.; Brooks, D. E.

    2016-02-01

    Progesterone (Pro) is a potent neurosteroid and promotes recovery from moderate Traumatic Brain Injury but its clinical application is severely impeded by its poor water solubility. Here we demonstrate that reversibly binding Pro within hydrophobically modified hyperbranched polyglycerol (HPG-Cn-MPEG) enhances its solubility, stability and bioavailability. Synthesis, characterization and Pro loading into HPG-Cn-MPEG is described. The release kinetics are correlated with structural properties and the results of Differential Scanning Calorimetry studies of a family of HPG-Cn-MPEGs of varying molecular weight and alkylation. While the maximum amount of Pro bound correlates well with the amount of alkyl carbon per molecule contributing to its hydrophobicity, the dominant first order rate constant for Pro release correlates strongly with the amount of structured or bound water in the dendritic domain of the polymer. The results provide evidence to justify more detailed studies of interactions with biological systems, both single cells and in animal models.Progesterone (Pro) is a potent neurosteroid and promotes recovery from moderate Traumatic Brain Injury but its clinical application is severely impeded by its poor water solubility. Here we demonstrate that reversibly binding Pro within hydrophobically modified hyperbranched polyglycerol (HPG-Cn-MPEG) enhances its solubility, stability and bioavailability. Synthesis, characterization and Pro loading into HPG-Cn-MPEG is described. The release kinetics are correlated with structural properties and the results of Differential Scanning Calorimetry studies of a family of HPG-Cn-MPEGs of varying molecular weight and alkylation. While the maximum amount of Pro bound correlates well with the amount of alkyl carbon per molecule contributing to its hydrophobicity, the dominant first order rate constant for Pro release correlates strongly with the amount of structured or bound water in the dendritic domain of the polymer. The

  10. Waktu Inseminasi Buatan yang Tepat pada Sapi Bali dan Kadar Progesteron pada Sapi Bunting (THE OPTIMUM TIME FOR ARTIFICIAL INSEMINATION IN BALI CATTLE AND THE PROGESTERONE LEVEL IN PREGNANT COW

    Directory of Open Access Journals (Sweden)

    Tjok Gde Oka Pemayun

    2014-10-01

    Full Text Available This study aims were to determine the proper time for insemination and the progesterone level ofpregnant Bali cattle. Complete randomized design method was used in this study. The study consisted ofthree treatment groups i.e. Group I, animals were inseminated at 0 hour (on estrus, group II, inseminatedat 12 h post-estrus and group III inseminated at 24 h post-estrus. Estrus was observed two times a day ie.in the morning (6:00 to 8:00 am and afternoon (16:00 to 18:00 pm which was characterized by transparentvaginal discharge. The results showed that the highest percentage of pregnancy occurred when the cattlewere inseminated at 24 h post-estrus (100%, however, statistically this was not significant different (P>0.05 to animals that were inseminated at 12 h post-estrus (75%. Moreover, no pregnancy (0% wasobserved in cattle that were inseminated at estrus. The progesterone level of pregnant bali cattle increasedas the period of gestation increased, being 15.43 ± 0.50 ng/mL at 30 days of gestation, 17.16 ± 0.34 ng/mLat 60 days of gestation and 20.78 ± 0.59 ng/mL at 90 days of gestation. In conclusion, the best time forinsemination in Bali cattle is at 24 h post-estrus and progesterone level seems to increase as the older thegestation period.

  11. Continuous versus cyclic progesterone exposure differentially regulates hippocampal gene expression and functional profiles.

    Directory of Open Access Journals (Sweden)

    Liqin Zhao

    Full Text Available This study investigated the impact of chronic exposure to continuous (CoP4 versus cyclic progesterone (CyP4 alone or in combination with 17β-estradiol (E2 on gene expression profiles targeting bioenergetics, metabolism and inflammation in the adult female rat hippocampus. High-throughput qRT-PCR analyses revealed that ovarian hormonal depletion induced by ovariectomy (OVX led to multiple significant gene expression alterations, which were to a great extent reversed by co-administration of E2 and CyP4. In contrast, co-administration of E2 and CoP4 induced a pattern highly resembling OVX. Bioinformatics analyses further revealed clear disparities in functional profiles associated with E2+CoP4 and E2+CyP4. Genes involved in mitochondrial energy (ATP synthase α subunit; Atp5a1, redox homeostasis (peroxiredoxin 5; Prdx5, insulin signaling (insulin-like growth factor I; Igf1, and cholesterol trafficking (liver X receptor α subtype; Nr1h3, differed in direction of regulation by E2+CoP4 (down-regulation relative to OVX and E2+CyP4 (up-regulation relative to OVX. In contrast, genes involved in amyloid metabolism (β-secretase; Bace1 differed only in degree of regulation, as both E2+CoP4 and E2+CyP4 induced down-regulation at different efficacy. E2+CyP4-induced changes could be associated with regulation of progesterone receptor membrane component 1(Pgrmc1. In summary, results from this study provide evidence at the molecular level that differing regimens of hormone therapy (HT can induce disparate gene expression profiles in brain. From a translational perspective, confirmation of these results in a model of natural menopause, would imply that the common regimen of continuous combined HT may have adverse consequences whereas a cyclic combined regimen, which is more physiological, could be an effective strategy to maintain neurological health and function throughout menopausal aging.

  12. Parturition induction in ewes by a progesterone receptor blocker, aglepristone, and subsequent neonatal survival: Preliminary results.

    Science.gov (United States)

    Özalp, R G; Yavuz, A; Orman, A; Seker, I; Udum Küçükşen, D; Rişvanlı, A; Demiral, Ö O; Wehrend, A

    2017-01-01

    The clinical effects of aglepristone treatment to induce parturition in ewes and their newborns were reported. Three experimental groups were defined: group AG5 (n = 5), group AG10 (n = 5), and group CG (n = 5) in which ewes were injected twice with 5, 10 mg/kg of aglepristone, and saline solution of ewes, respectively. Different parameters associated with parturition in ewes and their newborns were investigated. Serum progesterone, oxytocin, and free and conjugated total estrogens were measured after treatments until parturition. No statistical difference was found from first aglepristone administration to onset of lambing between AG5 and AG10 (23.90 ± 6.20, 40.00 ± 6.71 hours). Parturition induction in two groups shortened the gestational length significantly compared with the control group (P = 0.003). Dystocia was observed in two ewes in group AG10. The placental weight showed statistically significant difference only between the AG10 and CG (P = 0.039), but no difference was observed in the placental expulsion period between the groups. Decrease in food consumption 24 to 36 hours after parturition in all ewes and skin necrosis in an ewe in group AG5 were observed. Progesterone concentration was significantly lower in AG5 than that in ewes in group AG10 and CG (P birth weight (4.29 ± 0.28 kg), which was significantly different from the induced groups. No significant difference of blood pH and blood gases values between groups was identified both at birth and 12 hours after parturition for lambs. Significant differences could clearly be observed in total protein and blood urea nitrogen and total protein findings 12 hours after parturition (P control lambing time without any side effects in either mothers or lambs. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Microarray profiling of progesterone-regulated endometrial genes during the rhesus monkey secretory phase

    Directory of Open Access Journals (Sweden)

    Okulicz William C

    2004-07-01

    Full Text Available Abstract Background In the endometrium the steroid hormone progesterone (P, acting through its nuclear receptors, regulates the expression of specific target genes and gene networks required for endometrial maturation. Proper endometrial maturation is considered a requirement for embryo implantation. Endometrial receptivity is a complex process that is spatially and temporally restricted and the identity of genes that regulate receptivity has been pursued by a number of investigators. Methods In this study we have used high density oligonucleotide microarrays to screen for changes in mRNA transcript levels between normal proliferative and adequate secretory phases in Rhesus monkey artificial menstrual cycles. Biotinylated cRNA was prepared from day 13 and days 21–23 of the reproductive cycle and transcript levels were compared by hybridization to Affymetrix HG-U95A arrays. Results Of ~12,000 genes profiled, we identified 108 genes that were significantly regulated during the shift from a proliferative to an adequate secretory endometrium. Of these genes, 39 were up-regulated at days 21–23 versus day 13, and 69 were down-regulated. Genes up-regulated in P-dominant tissue included: secretoglobin (uteroglobin, histone 2A, polo-like kinase (PLK, spermidine/spermine acetyltransferase 2 (SAT2, secretory leukocyte protease inhibitor (SLPI and metallothionein 1G (MT1G, all of which have been previously documented as elevated in the Rhesus monkey or human endometrium during the secretory phase. Genes down-regulated included: transforming growth factor beta-induced (TGFBI or BIGH3, matrix metalloproteinase 11 (stromelysin 3, proenkephalin (PENK, cysteine/glycine-rich protein 2 (CSRP2, collagen type VII alpha 1 (COL7A1, secreted frizzled-related protein 4 (SFRP4, progesterone receptor membrane component 1 (PGRMC1, chemokine (C-X-C ligand 12 (CXCL12 and biglycan (BGN. In addition, many novel/unknown genes were also identified. Validation of array data

  14. Mig-6 regulates endometrial genes involved in cell cycle and progesterone signaling

    Energy Technology Data Exchange (ETDEWEB)

    Yoo, Jung-Yoon; Kim, Tae Hoon; Lee, Jae Hee [Department of Obstetrics, Gynecology & Reproductive Biology, Michigan State University, Grand Rapids, MI (United States); Dunwoodie, Sally L. [Developmental and Stem Cell Biology Division, Victor Chang Cardiac Research Institute, Darlinghurst, New South Wales 2010 (Australia); St. Vincent' s Clinical School and the School of Biotechnology and Biomolecular Sciences, University of New South Wales, Kensington, New South Wales 2033 (Australia); Ku, Bon Jeong, E-mail: bonjeong@cnu.ac.kr [Department of Internal Medicine, Chungnam National University School of Medicine, Daejeon (Korea, Republic of); Jeong, Jae-Wook, E-mail: JaeWook.Jeong@hc.msu.edu [Department of Obstetrics, Gynecology & Reproductive Biology, Michigan State University, Grand Rapids, MI (United States); Department of Women' s Health, Spectrum Health System, Grand Rapids, MI (United States)

    2015-07-10

    Mitogen inducible gene 6 (Mig-6) is an important mediator of progesterone (P4) signaling to inhibit estrogen (E2) signaling in the uterus. Ablation of Mig-6 in the murine uterus leads to the development of endometrial hyperplasia and E2-induced endometrial cancer. To identify the molecular pathways regulated by Mig-6, we performed microarray analysis on the uterus of ovariectomized Mig-6{sup f/f} and PGR{sup cre/+}Mig-6{sup f/f} (Mig-6{sup d/d}) mice treated with vehicle or P4 for 6 h. The results revealed that 772 transcripts were significantly regulated in the Mig-6{sup d/d} uterus treated with vehicle as compared with Mig-6{sup f/f} mice. The pathway analysis showed that Mig-6 suppressed the expression of gene-related cell cycle regulation in the absence of ovarian steroid hormone. The epithelium of Mig-6{sup d/d} mice showed a significant increase in the number of proliferative cells compared to Mig-6{sup f/f} mice. This microarray analysis also revealed that 324 genes are regulated by P4 as well as Mig-6. Cited2, the developmentally important transcription factor, was identified as being regulated by the P4-Mig-6 axis. To determine the role of Cited2 in the uterus, we used the mice with Cited2 that were conditionally ablated in progesterone receptor-positive cells (PGR{sup cre/+}Cited2{sup f/f}; Cited2{sup d/d}). Ablation of Cited2 in the uterus resulted in a significant reduction in the ability of the uterus to undergo a hormonally induced decidual reaction. Identification and analysis of these responsive genes will help define the role of P4 as well as Mig-6 in regulating uterine biology. - Highlights: • We identify Mig-6- and P4-regulated uterine genes by microarray analysis. • Mig-6 suppresses cell cycle progression and epithelial cell proliferation in uterus. • We identify the Mig-6 dependent induced genes by P4. • Cited2 plays an important role for decidualization as a P4 and Mig-6 target gene.

  15. Fertirelin and buserelin compared by LH release, milk progesterone and subsequent reproductive performance in dairy cows treated for follicular cysts.