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)

Histological changes were studied in the ovary and uterus of rats receiving different doses of Depo-Provera (DMPA) and Noristerat (NET-EN) for varying duration. The effect of DMPA on ovarian and uterine tissues was strongly progestational. The whole morphological alteration in the ovary after DMPA therapy appeared to be the atresia of the follicular apparatus with degeneration of the growing follicles. Uterine histology reflected that endometrial tissues gradually became inactive and with prolonged treatment at high doses, atrophy of the endometrium was noted. In NET-EN-treated rats, absence of mature follicles and recent corpora lutea reflected the blockade of ovulation. There was no extreme atrophy of the ovary or endometrium as found with DMPA treatment. With higher doses of NET-EN, endometrial growth was arrested.
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PMID:Histological changes in the ovary and uterus of rat after injectable contraceptive therapy. 297 Mar 68

The change of resistance in the uterine arteries was studied in 20 patients showing a normal involution on five consecutive days. A uterine artery was examined by Doppler sonography, the Doppler profile evaluated, and the quotient, Fmean, resistance index, and pulsatility index were calculated from the systole and diastole. These parameters, which provided information on vascular resistance independently of the angle between the Doppler beam and the vessel, indicated a continuous increase during the puerperium; the differences in values for different days were significant. The changes in the Doppler profiles in the puerperial period pointed to an increasing vascular resistance. In one-half of the patients this was shown only by an increasing slope to the systolic peak, a sharp drop to early diastole, and a clear distinction between systole and diastole. In the other half of the patients the Doppler curves were like those found in pregnant patients with EPH gestosis. This indicated that the pathologic mechanisms leading to increased resistance in the uterine vessels were the same in both groups. One cause of this may be contraction and compression of the blood vessels, the other, and probably principal, cause was reduction of the vascular system due to histolysis, as in the puerperium, or insufficient development of the vascular system, as in EPH gestosis. That is to say, functional and morphological changes occur in both cases. No decrease in resistance in the uterine vascular bed was detected in cases of puerperial subinvolution of the uterus.
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PMID:[Involution-induced changes in arterial uterine blood flow]. 306 54

The present study was designed to characterize the dynamics of progestin metabolism peripherally and across the uterus during normal baboon pregnancy and to determine whether the decline in placental progesterone (P4) production which results from administration of the antiestrogen ethamoxytriphetol (MER-25) to baboons reflects a decrease in conversion of pregnenolone (P5) to P4 and thus delta 5-3 beta-hydroxysteroid dehydrogenase activity. To examine this possibility, the conversion of [3H]P5 to [3H]P4 was determined by the constant infusion method on day 100 (midgestation) and day 175 (near term) of gestation in baboons that received MER-25 (25 mg/day X kg BW, po) on days 95-100 or 140-175 (term = 184 days). Baboons were sedated with ketamine HCl, then received a constant iv infusion of [3H]P5 (1.0 mu Ci/0.388 ml X min) and [14C]P4 (0.2 mu Ci/0.388 ml X min for 110 min. Radiolabeled progestins were purified from blood samples withdrawn from saphenous, uterine, and umbilical vessels, and the MCR of P4 and P5, uterine extraction of P5, and transfer constants (rho) for the peripheral, transuterofetoplacental, and transuteroplacental conversion of P5 to P4 were determined. The formation of P4 from P5 by incubates of placental cells obtained on day 175 from untreated and MER-25-treated baboons was also assessed. During normal baboon pregnancy the mean (+/- SE) % P5 extracted (i.e. metabolized) by the uterus was 31.0 +/- 3.3 at midgestation and 45.7 +/- 5.6 late in gestation. Peripheral and transuterofetoplacental rho values of P5 to P4 in untreated baboons were 6.9 +/- 1.8% and 37.3 +/- 7.9%, respectively, at midgestation and 6.1 +/- 0.6% and 46.8 +/- 10.1%, respectively, near term. The transuteroplacental rho of P5 to P4 was only slightly lower than the transuterofetoplacental values, indicating minimal conversion of P5 to P4 by the fetus. The peripheral contribution of P5 production to the total production rate of P4 at term in baboons was 1%. The contribution of uteroplacental conversion of P5 to P4 to the total conversion of P5 to P4 at midgestation was estimated to be 22%. MER-25 caused a 53% decline (P less than 0.01) in serum P4 concentrations from a mean (+/- SE) of 12.5 +/- 2.4 ng/ml during the pretreatment period to 5.4 +/- 0.3 ng/ml between days 140 and 175 of gestation.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Transuterofetoplacental conversion of pregnenolone to progesterone in antiestrogen-treated baboons. 365 27

Experiments were conducted to determine why tamoxifen, a non-steroidal antiestrogen, is uterotrophic in mice, whereas MER-25 (ethamoxytriphetol), a structurally related compound, is antiuterotrophic. Initial experiments indicated that the pituitary was not required for a uterotrophic response in mice to either estradiol (E2), tamoxifen (TAM), or 4-hydroxytamoxifen (4-OH-TAM) MER-25 was not uterotrophic in mice but was capable of completely inhibiting the uterotrophic responses of mice to estrogens (E2) as well as antiestrogens (TAM and 4-OH-TAM); this inhibition was reversible by increasing the dose of the antiestrogen (TAM). The relative binding affinities (RBA) of TAM, 4-OH-TAM, and MER-25 to mouse uterus estrogen receptor (ER) and mouse liver antiestrogen binding sites (AEBS) were compared to determine whether either (or both) of these sites mediate the biological effects of these compounds. E2 is arbitrarily assigned an RBA of 100 for ER; similarly, TAM is assigned an RBA of 100 for AEBS. MER-25 bound to AEBS with an RBA of 8.9 and to ER with an RBA of less than 0.06; in contrast, TAM and 4-OH-TAM bound to AEBS with RBAs of 100 and 53, respectively, and to ER with RBAs of 2 and 131, respectively. Five other compounds that had similar RBAs as MER-25 for AEBs (RBAs in the range 4-9) and for ER (RBAs less than 0.06) were tested for their antiuterotrophic activities in vivo against both estrogen (E2) and antiestrogen (TAM) in ovariectomized mice. None of these compounds were antiuterotrophic against either estradiol or tamoxifen (P less than 0.01), nor were any of the compounds uterotrophic in mice. These data suggest that differences in the biological actions of tamoxifen and MER-25 in mice are not mediated through AEBS and are most likely due to differences in their interactions with ER.
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PMID:Possible mechanisms for the agonist actions of tamoxifen and the antagonist actions of MER-25 (ethamoxytriphetol) in the mouse uterus. 401 16

Neutral endopeptidase (NEP; EC 3.4.24.11), an enzyme which metabolizes several peptides (including oxytocin and endothelins) implicated in the control of uterine function, was found to be localized in the ovine uterus throughout the oestrous cycle and in the uterus and conceptus during early pregnancy, using immunohistochemical techniques. Positive NEP immunoreactivity was found in the endometrium principally in stromal cells, in the vasculature in endothelial and vascular smooth muscle cells, and also weakly in some glandular epithelial cells. In a layer of stromal fibroblasts several cells in thickness underlying the luminal epithelium, staining was much weaker than that in the deeper stromal cells throughout the period examined. NEP staining was also present in smooth muscle cells of the myometrium at all times, and was most intense in the layer of cells adjacent to the endometrium. In the conceptus, NEP immunohistochemical staining was found in uninucleate cells, but not in binucleate trophoblast cells, in epithelial cells of the allantois and amnion, and in the heart and brain of the Day-20 embryo. In ovariectomized ewes treated with oestrogen or progesterone separately or remaining untreated, immunohistochemical staining of NEP was stronger when compared with intact ewes, in caruncular and intercaruncular stroma and epithelia, in glands, in the vasculature and in myometrium. The staining was less intense in all cell types in ewes receiving oestrogen plus progesterone. The expression of NEP and its specific regionalization within the uterus indicate a mechanism by which the availability of biologically important peptides involved in the regulation of the oestrous cycle and implantation, including oxytocin and endothelin, can be controlled by regulation of their metabolism.
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PMID:Localization of neutral endopeptidase in the ovine uterus and conceptus during the oestrous cycle and early pregnancy. 756 53

Insulin-like growth factor binding protein-1 (IGFBP-1) is expressed primarily in the liver, kidney, and uterus. Basal IGFBP-1 promoter activity in human HEP G2 hepatoma cells is dependent upon a proximal promoter element that binds hepatic nuclear factor 1 (HNF1), a protein that is likely to be an important factor regulating the expression of many genes in liver and kidney. To test whether HNF1 activates IGFBP-1 transcription, HEP G2 cells and HeLa cells were cotransfected transiently with HNF1 expression vectors and with IGFBP-1 promoter/chloramphenicol acetyltransferase reporter gene constructs. HNF1 increased IGFBP-1 promoter activity in both HEP G2 and HeLa cells. Gel mobility-shift assays and additional transfections in HeLa cells showed that expressed full-length and carboxy-terminal truncated forms of HNF1 could each bind the HNF1 cis element of the IGFBP-1 promoter; however, significant trans-activation only occurred in the presence of the full-length HNF1 protein, similar to past experience with these two HNF1 forms and the albumin promoter. Further studies showed that IGFBP-1 promoter constructs containing mutations with high or low affinity for HNF1 responded to HNF1 expression with increased or decreased activity, respectively, relative to the native promoter. These studies suggest that HNF1 and/or related proteins play a role in hepatic, and perhaps also renal, expression of IGFBP-1.
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PMID:HNF1 activates transcription of the human gene for insulin-like growth factor binding protein-1. 768 29

In pregnancy calcium antagonism is of great importance. The uterus-relaxing properties of verapamil are well known, diltiazem shows an excellent tokolytic efficacy and is also effective as hypotensive in pregnancy-induced hypotension. In contrast to verapamil and diltiazem the dihydropyridines were not clinically successful as tokolytic or hypotensive in pregnancy. Magnesium is a therapy of first choice in the EPH-gestosis.
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PMID:[Calcium antagonists in pregnancy as an antihypertensive and tocolytic agent]. 813 35

In most mammals studied, a substantial numbers of preimplantation embryos are believed to be lost in vivo. In vitro, embryos develop slowly and lose viability. Hence, there is a need to assess the extent and cause of embryonic loss both in vivo and in vitro. In this study, we assessed the quality of in vivo produced ovulation products/embryos, recovered on days 1-5 pregnancy, from naturally bred wistar rats. From day 1 pregnant rats (n = 24), 226 ovulation products were recovered which included 52% (117) unfertilized oocytes and empty zonae with/without cell debris (UFO-EZ:CD) and 48% (109) 1-cells. Flushings of day 2 rats (n = 27) contained 229 ovulation products, consisting of 70% (160) 2-cells and 30% (69) UFO-EZ:CD. Flushings of day 3 rats (n = 27) had 23% (56) 2-cells, 6% (15) 3-cells, 23% (57) 4-cells, 1% (2) 5-7 cells, 2% (5) 8-cells and 45% (112) UFO-EZ:CD, total being 247. Flushings of day 4 rats (n = 28) had 193 ovulation products comprising of one morula, 45% (86) 8-cells, 5% (9) 5-7-cells and the rest were 4-cells (2), 3-cells (2), 2-cells (1) and 48% (92) UFO-EZ:CD. Day 5 flushings (n = 27) had 202 ovulation products which included 13% (27) morulae, 17% (34) early, 36% (73) mid and 2% (5) late blastocysts; additionally, 4-cells (1), 8-cells (2) and 30% (60) UFO-EZ:CD were also recovered. On day 4, embryos (8-cells) migrated from the oviduct to the uterus. When pregnant rats (n = 25) were allowed to term, only 15 females (60%) delivered pups (128) with variable litter size (2-12). These results indicate that 56% (619/1097) of recovered rat preimplantation embryos are of expected developmental age with a mixture of asynchronously cleaving embryos. The remaining 44% (478) is comprised of 38% (417) UFO-EZ:CD and 6% (61) abnormal and developmentally retarded embryos, which are unlikely to produce viable pups at term.
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PMID:Assessment of developmental retardation and abnormality of in vivo produced preimplantation embryos in rat. 871 73

Vascular permeability factor (VPF), also known as vascular endothelial growth factor (VEGF), is an angiogenic factor with important roles in tumor growth, wound healing, and inflammation. VPF/VEGF interacts with endothelial cells by way of two high-affinity receptor tyrosine kinases: flt-1 and KDR. The vast majority of published studies have described expression of the VPF/VEGF receptors only in endothelial cells, and the statement is frequently made that these receptors are endothelial-cell-specific. In this study, we detected mRNA for flt-1 and KDR by in situ hybridization in smooth muscle cells in sections of the wall of the uterus. To confirm these unexpected findings, smooth muscle cells from the uterus and, as a control, from the colon were isolated, characterized, and cultured. Both uterine and colonic smooth muscle cells in culture expressed VPF/VEGF, but only smooth muscle cells from the uterus expressed mRNA for flt-1 and KDR by Northern analysis and in situ hybridization. Cell culture extracts of uterine but not colonic smooth muscle cells were also positive for flt-1 by Western analysis. Moreover, cultured uterine but not clonic smooth muscle cells phosphorylated the flt-1 receptor and proliferated strongly in response to added VPF/VEGF. This is one of the first rigorous demonstrations that a normal cell type other than endothelial cells can express functional receptors for VPF/VEGF in vivo and in vitro, suggesting that VPF/VEGF may have important, previously unsuspected roles on cell types other than endothelium.
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PMID:Uterine smooth muscle cells express functional receptors (flt-1 and KDR) for vascular permeability factor/vascular endothelial growth factor. 904 61

In this study, the histomorphological changes induced by 5 alpha-norethisterone (5 alpha-NET), a reduced metabolite of the contragestational postcoital agent norethisterone, in the oviduct and the uterus of the pregnant rabbit were determined. Adult fertilized rabbits were treated daily with 5 alpha-NET (1.0, 1.5, 2.5, and 5.0 mg/kg/day) during 7 consecutive days, starting from the first day after coitus. Twenty-four hours after the last administration, the histological analysis of the oviduct and the uterus was performed. It was observed that in the infundibulum-ampullae region as well as in the isthmus of the oviduct, the number of nonsecretory cells (PAS-negative) were decreased, whereas the number of secretory cells (PAS-positive) were increased significantly after 5 alpha-NET administration. The proportion of glandular tissue in the uterus markedly diminished in relation to that of the stromal tissue. This indicates an inhibition of the endometrial transformation observed during normal pregnancy. Interestingly, the highest doses of 5 alpha-NET (2.5 and 5.0 mg/kg/day) induced necrosis in the uterus but not in the oviduct. These results suggest that the molecular antiprogestational effects previously observed after 5 alpha-NET administration are also related to changes in the histomorphology of both the oviduct and the uterus of the pregnant rabbit.
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PMID:Differential effects of 5 alpha-norethisterone on the histomorphology of the oviduct and uterus of the pregnant rabbit. 967 43


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