Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.10.1 (ERK)
 95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aim of this study was to investigate the potential of UDMA/HEMA mixtures as priming and sealing components of dental adhesives. The monomers were mixed in weight ratios 100/0, 80/20, 60/40, 50/50, 40/60, 20/80, 10/90, and 0/100, light activated, and dissolved in acetone at equal parts. The 60/40 UDMA/HEMA mixture served as a reference which was modified with 5, 10, 20, and 30 parts 4-MET relative to the mass of the basic monomer mixture. Shear bond strengths (24 h) of resin composite cylinders, bonded with the adhesive monomers on human enamel and dentin, were determined following a total etch technique with phosphoric acid and application of the adhesives in 2 coats on moist tooth surfaces. Average bond strength to enamel was 32 MPa with no difference between the adhesives. On dentin, significantly different bond strengths were found between UDMA (12.9 MPA) and HEMA (19.4 MPa), whereas all binary mixtures' bond strengths were not significantly different (mean 16.2 MPa). Addition of 5 to 20 wt% 4-MET resulted in a significantly increased mean shear bond strength of 22.3 MPa on dentin. At 10%, a maximum mean strength of 25.4 MPa was recorded. It is concluded that mixtures of commonly used polymerizable monomers, characterized by hydrophilic moieties and dissolved in acetone, are promising candidates for effective resin bonding to enamel and dentin, provided application by the moist bonding technique.
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PMID:Resin bonding to enamel and dentin with one-component UDMA/HEMA adhesives. 915 Oct 72

The objectives of this study were to determine whether a new progesterone (P4)-releasing intravaginal insert would induce fertile estrus and whether FSH combined with the insert would increase prolificacy in anestrous ewes introduced to rams. Ewes of mixed breeding on six farms were assigned to four randomized treatments: control (C), n = 73; 12 d P4 (polycapralactone [PCL] insert with 0.82 g P4), (P12), n = 73; 12 d P4 plus i.m. FSH (Folltropin, 55 mg NIH-FSH-P1 equivalent) in propylene glycol, 24 h before insert removal, (P12F), n = 71; and 5 d P4 plus FSH (P5F), n = 77. Growth and ovulation of follicles were observed ultrasonographically in 20 ewes at four farms (five/treatment) at insert removal and 36, 48, 72, and 96 h later. Intact rams (1:15 ewes in multiple-sire groups) were joined at insert removal, and raddle marks were observed every 12 h for 5 d. On d 26 to 30, rams were removed; ewes were examined for pregnancy then and 20 d later. Percentage of ewes marked by rams was greater in P4-treated (66 to 79%) than in C (12%; P < 0.01) ewes and in P5F (79%) than in P12F (66%; P < 0.05). Diameters of largest follicles at insert removal were greater (P < 0.05) in P4-treated (5.5 +/- 0.2) than in C ewes (4.8 +/- 0.2). Progesterone increased numbers of follicles > 3 mm (P < 0.01) or ovulated (P < 0.05; 2.6 +/- 0.6 vs 1.3 +/- 0.6 in C ewes) and FSH increased number of follicles > 3 mm (P < 0.05). In FSH-treated ewes, ovulation rate tended to be greater after treatment with P4 for 5 than for 12 d (P = 0.09, 3.3 +/- 0.6 and 2.2 +/- 0.4, respectively). More P4-treated than C ewes lambed (P < 0.01) to the first (38 to 45 vs 0%) or both (63 to 66 vs 41%) service periods. Prolificacy (first service) did not differ between FSH-treated ewes (P12F + P5F; 1.8 +/- 0.1) and ewes treated with P4 only (P12; 1.6 +/- 0.1). However, FSH increased prolificacy to first service (1.8 +/- 0.1) over prolificacy to second service (C ewes 1.5 +/- 0.1; P < 0.05, and all ewes 1.4 +/- 0.1; P < 0.01). Pregnancy retention did not differ among treatments but was greater (P < 0.01) in ewes that conceived at the first (90.9 +/- 3.7) than at the second (72.5 +/- 3.3) service period. In conclusion, a PCL insert in combination with ram introduction at insert removal was more effective than ram introduction alone to induce synchronized estrus and ovulation and to yield pregnancy after one or two service periods. Treatment with P4 for 5 d was as effective as for 12 d to induce fertile estrus in FSH-treated anestrous ewes.
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PMID:Effectiveness of intravaginal progesterone inserts and FSH for inducing synchronized estrus and increasing lambing rate in anestrous ewes. 1137 30

We showed that decidualized stromal cells of luteal phase and pregnant human endometrium express tissue factor (TF), the primary initiator of hemostasis, thereby suggesting a mechanism by which perivascular decidual cells can mitigate the risk of hemorrhage during endovascular trophoblast invasion. Progestins enhanced TF mRNA and protein levels in monolayers of human endometrial stromal cells (HESCs), with estradiol (E2) + progestin, further enhancing TF levels despite a lack of response to E2 alone. This differential ovarian steroid response has been found for several decidualization markers. Further studies with cultured HESCs established that elevated TF levels are mediated by the progesterone receptor and are maintained for weeks in response to E2 plus progestin, thus simulating the chronic upregulation of TF levels observed in decidualized HESCs in vivo. Recent studies revealed that elevated TF expression during in vitro decidualization of HESCs involved both the EGFR and progesterone receptor. Thus, enhancement of TF mRNA and protein levels in the HESCs required co-incubation with a progestin (MPA) and an EGFR agonist such as EGF or TGF-alpha. In correspondence with co-elevation of EGFR and TF in decidualized HESCs in sections of luteal phase and pregnant endometrium, EGFR levels proved to be progestin-enhanced in the cultured HESCs. We established that progestin-enhanced TF expression in HESCs was trancriptionally regulated, then evaluated the relative roles of SP and EGR-1 sites on the TF promoter in regulating this expression. Transient transfections with a series of promoter constructs containing overlapping SP and EGR-1 sites and with constructs in which the EGR-1 and SP sites were systematically inactivated by site-directed mutagenesis established the dominance of SP sites in both basal and progestin-enhanced TF transcriptional activity. Additional experiments involving transient transfections with SPloverexpressing vectors and with a specific blocker of if Sp1 binding to its corresponding GC box specified the importance of the Sp1 transcription factor. These results were further validated by immunostaining, which revealed that the ratio of Sp1 to Sp3 increased during progestin-regulated decidualization of HESCs in vitro and in vivo. The absence of canonical estrogen and progesterone response elements from either the TF or Sp1 gene promoters suggests that the EGFR may help to mediate progestin-enhanced TF expression during decidualization of HESCs.
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PMID:Decidual cell-expressed tissue factor maintains hemostasis in human endometrium. 1159 61

Mammary gland development is regulated by complex interactions among mammogenic hormones and locally derived paracrine growth factors. In epithelial tissues, keratinocyte growth factor (KGF or FGF-7) originates in the stroma while its receptor (KGFR or FGFR2-IIIb) is present only in the epithelium. Previous work showed that estrogen but not progesterone could stimulate the synthesis of KGF in mammary stroma in vivo. The effects of 17 beta-estradiol and progesterone on KGFR expression in vivo were examined in these studies. Peripubertal and mature virgin mice received subcutaneous injections of hormone in sesame oil after which KGFR mRNA levels were assayed by ribonuclease protection analysis of mammary gland RNA. Estradiol treatment caused a dose- and time-dependent decrease in KGFR mRNA level in mice from both age groups while stimulating ductal growth after 7 days of treatment. Inhibition of KGFR expression was near maximal at an estradiol dose of 2 microg after 1 day of treatment. Progesterone injection increased KGFR mRNA levels but this effect correlated with the stimulation of ductal growth. However, when progesterone was co-administered with estradiol, KGFR mRNA levels were maintained in the absence of any effect on ductal growth. Thus, estradiol inhibited KGFR mRNA only when elevated unopposed by progesterone. These data show that KGFR expression is determined by the ratio of estradiol and progesterone and suggests a mechanism through which these hormones can co-operate to optimize their growth-promoting effects. Consequences of hormone imbalance are also implicated.
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PMID:In vivo inhibition of keratinocyte growth factor receptor expression by estrogen and antagonism by progesterone in the mouse mammary gland. 1169 52

Progestin-only injectables are among the most effective and safe of all contraceptives, yet they are not widely used in many countries. This limited use is in part due to a lack of accurate information about health concerns, inadequate counseling for users about managing side effects, and their limited availability. Where they are available, progestin-only injectables rapidly become one of the preferred methods. Depot-medroxyprogesterone acetate (DMPA) and norethindrone enanthate (NET-EN) are the two progestin-only injectables in use worldwide. The former drug is sold under the brand name Depo-Provera, and the latter as Noristerat. DMPA is delivered in a water-based, crystalline suspension and absorbed gradually by the body. The normal injection of 150 mg is intended to be administered every three months, but contraceptive protection continues for an additional two weeks to provide a grace period for women who are late receiving their next injection. NET-EN is an oily solution which requires a larger needle than DMPA for injection. A 200 mg injection of NET-EN is usually administered every two months. Both of these safe, highly effective drugs are injected in either the upper arm or buttocks. DMPA and NET-EN can be distributed easily in nonclinical settings where nonphysicians can provide them to clients. The main disadvantage of the method is the disruption of the menstrual cycle, but that is generally not a serious medical problem. Focusing mainly upon DMPA, this article includes discussion of menstrual irregularity, the reduced risk of endometrial cancer among DMPA users, and method availability.
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PMID:Progestin-only injectables offer many advantages. 1228 28

We have previously shown that the G protein-coupled receptor (GPR)30 is critical for progestin-induced growth inhibition. In this study, we addressed signal transduction pathways involved in progestin-mediated signaling. Progestin could not provide any additional growth inhibitory effect to MCF-7 cells treated with specific MAPK kinase inhibitors, PD98059 and U0126. Medroxyprogesteroneacetate (MPA) induced a late (22-23 h) decrease in ERK-1 and -2 activities verified by immunoblotting and kinase assay. The inactivation was abrogated by antiprogestin. Transient expression of GPR30 decreased ERK-1 and -2 activity; and in the cells in which GPR30 expression was decreased by the antisense, ERK activities were increased. The antisense-expressing cells were able to significantly resist the growth-inhibitory effect of the MAPK kinase inhibitors PD98059 and U0126 but not that of other factors tested. Interestingly, the decrease of ERK activity induced by MPA was abrogated by GPR30 antisense. Collectively, these results show that MAPK activity is inhibited by progestin and GPR30 and suggest that progestin-induced ERK inactivation is mediated through GPR30. Coupled with our previous findings, the data imply that up-regulation of GPR30 by progestin leads to ERK-1 and -2 inactivation associated with MPA-induced growth inhibition.
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PMID:Progestin and G protein-coupled receptor 30 inhibit mitogen-activated protein kinase activity in MCF-7 breast cancer cells. 1244 89

The major objective of this experiment was to determine whether the bovine placenta could be stimulated to secrete progesterone, since the bovine placenta secretes little progesterone when the corpus luteum is functional. Secondly, we wanted to determine whether reported abortifacients or progesterone or estrogen receptor antagonists affected bovine placental prostaglandin secretion. The ovine placenta secretes half of the circulating progesterone at day 90 of pregnancy and PGE2 appears to regulate ovine placental progesterone secretion. Calcium has been reported to regulate placental progesterone secretion in cattle. Diced 186-245-day placental slice explants from six Brahman and six Angus cows were incubated in vitro at 39.5 degrees C under 95% air: 5% CO2 at pH 7.2 in 5 ml of M-199 for 1 h in the absence of treatments and for 4 and 8 h in the presence of treatments. Treatments were: vehicle; R24571; compound 48/80; IP3; PGE2; CaCl2; cyclosporin A; lipopolysaccharide (endotoxin) from Salmonella abortus equi., enteriditis, and typhimurium; monensin; ionomycin; arachidonic acid; mimosine; palmitic acid; progesterone, androstenedione; estradiol-17beta; A23187; RU-486; or MER-25. Jugular and uterine venous plasma and culture media were analyzed for progesterone, PGE2 and PGF2alpha by radioimmunoassay (RIA). Plasma hormone data were analyzed by a One-Way Analysis of Variance (ANOVA). Hormone data in culture media were analyzed for breed and treatment effects by a Factorial Design (2 breeds, 2-range of days, 21 treatments) for ANOVA (2 x 2 x 21). Since hormone data secreted by placental tissue in vitro did not differ (P > or = 0.05) by breed or range of days of pregnancy, data were pooled and analyzed by a One-Way ANOVA. Concentrations of PGE2 in uterine venous blood were two-fold greater (P < or = 0.05) in Angus than Brahman cows. PGE2 and PGF2alpha in vehicle controls increased from 4 to 8h (P < or = 0.05), but not progesterone (P > or = 0.05) Progesterone in culture media treated with RU-486 increased (P < or = 0.05) at 4 and 8 h compared to vehicle controls and was not affected by other treatments (P > or = 0.05). Concentrations of PGE2 in media at 4 and 8 h were lower (P < or = 0.05) when compared to controls except treatment with PGE2 at 4 and 8h and RU-486 at 8h (P > or = 0.05). PGF2alpha was increased (P < or = 0.05) by RU-486 at 8h and no other treatment affected PGF2alpha at 4 or 8 h (P < or = 0.05). In conclusion, modulators of cellular calcium signalling pathways given alone do not affect bovine placental progesterone secretion at the days studied and progesterone receptor-mediated events appear to suppress placental progesterone, PGF2alpha, and PGE2 secretion in cattle. In addition, PGE2 does not appear to regulate bovine placental progesterone secretion when the corpus luteum is functional and bacterial endotoxin does not appear to affect bovine placental secretion of PGF2alpha or PGE2.
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PMID:Do calcium-mediated cellular signalling pathways, prostaglandin E2 (PGE2), estrogen or progesterone receptor antagonists, or bacterial endotoxins affect bovine placental function in vitro? 1528 56

The angiopoietin (ANGPT)-receptor (TEK) system plays a crucial role in blood vessel formation and stability. Because the endogenous agonist ANGPT1, antagonist ANGPT2, and TEK are expressed in the primate ovary, experiments were designed to investigate their role at a critical time during tissue remodeling/ angiogenesis in the menstrual cycle (i.e., at midcycle during maturation, ovulation, and luteinization of the dominant follicle). Either vehicle, 20 microg of ANGPT1, 2 microg of ANGPT2 (low-dose), or 20 microg of ANGPT2 (high-dose) was injected directly into the preovulatory follicle of monkeys around the day (-1 to 0) of the midcycle estradiol (E2)/LH peak. Ovaries were evaluated on Day 3 postinjection for follicle rupture, and serum samples were analyzed for levels of E2 and progesterone. Similar to controls, ANGPT1 treatment was followed by ovulation, and elevated progesterone levels during the luteal phase. In contrast, high-dose ANGPT2 treatment prevented follicle rupture, and progesterone levels never rose above baseline in the subsequent 12 days. However, an E2 peak typically occurred 12 days postinjection. Laparoscopy detected a preovulatory follicle on the contralateral (noninjected) ovary. Progesterone levels subsequently increased above baseline in these animals. Thus, exogenous ANGPT2 disrupted maturation of the preovulatory follicle, preventing its ovulation and conversion into the corpus luteum. ANGPT antagonism eliminated the dominant structure, thereby resetting the ovarian cycle, with selection and maturation of the next preovulatory follicle occurring in a timely manner. The data are consistent with a critical role of the ANGPT-TIE1/TEK system in the ovary, notably at the late stages of follicle maturation during the menstrual cycle.
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PMID:Local delivery of angiopoietin-2 into the preovulatory follicle terminates the menstrual cycle in rhesus monkeys. 1570 73

Microporous, poly(epsilon-caprolactone) (PCL) matrices were loaded with progesterone by precipitation casting using co-solutions of PCL and progesterone in acetone. Progesterone loadings up to 32% w/w were readily achieved by increasing the drug content of the starting PCL solution. The kinetics of steroid release in PBS at 37 degrees C over 10 days could be described effectively by a diffusional release model although the Korsmeyer-Peppas model indicated the involvement of multiple release phenomena. The diffusion rate constant (D) increased from 8 to 24 microg/mg matrix/day0.5 as the drug loading increased from 3.6 to 12.4% w/w. A total cumulative release of 75%-95% indicates the high efficiency of steroid delivery. Increasing the matrix density from 0.22 to 0.39 g/cm3, by increasing the starting PCL solution concentration, was less effective in changing drug release kinetics. Retention of anti-proliferative activity of released steroid was confirmed using cultures of breast cancer epithelial (MCF-7) cells. Progesterone released from PCL matrices into PBS at 37 degrees C over 14 days retarded the growth of MCF-7 cells by a factor of at least 3.5 compared with progesterone-free controls. These findings recommend further investigation of precipitation-cast PCL matrices for delivery of bioactive molecules such as anti-proliferative agents from implanted, inserted or topical devices.
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PMID:Precipitation casting of drug-loaded microporous PCL matrices: incorporation of progesterone by co-dissolution. 1599 8

The objective of this study was to determine the effectiveness of transrectal ultrasonography and serum progesterone (P(4)), estrone sulfate (E(1)S) and pregnancy-specific protein B (PSPB), without prior knowledge of reproductive status, in detecting pregnancy in elk cows. In addition, body weight and body condition score (BCS) were determined to assess whether body condition affects pregnancy status in elk cows. Twenty-five elk cows were sampled during the early rut (Period 1) and after the rut (Period 2), an interval of 120 d. Age, weight, BCS and blood samples, for P(4), E(1)S and PSPB determinations, were taken at Periods 1 and 2. Ultrasonography was performed at Period 2. The younger elk cows weighed less (P<0.05) than older cows. However, pregnancy status was not affected (P> 0.10) by age or weight of the cow. Elk cows that calved had higher (P<0.02) BCS at Periods 1 and 2 than cows that remained open. Serum P(4) and E(1)S were higher (P<0.0001) in pregnant cows at Period 2 than in open cows. Progesterone was 85.8% accurate in detecting pregnant versus open cows at Period 1, while E(1)S and PSPB were not effective. Elk cows at Period 1 were <20 d pregnant with the exception of 1 cow at 46 d. Ultrasonography was 92% accurate, P(4) was 95% accurate, and E(1)S and PSPB were both 100% accurate in determining pregnant versus open cows at Period 2. Pregnant cows at Period 2 were all > 100 d pregnant. Ultrasonography, serum E(1)S and PSPB all may provide a reliable means for pregnancy diagnosis in elk cows at > 100 d of gestation, while serum P(4) may be effective when multiple samples are compared during or after the rut, or when used in combination with the other diagnostic methods described. Further research is needed to determine the optimum time period after breeding in elk cows for accurate pregnancy detection through hormonal analysis.
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PMID:Methods for pregnancy determination and the effects of body condition on pregnancy status in Rocky mountain elk (Cervus elephus nelsoni ). 1672 13


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