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PubMed1993

Characterization of muscarinic receptors in guinea-pig uterus.

To characterize the muscarinic receptor present in guinea-pig uterus smooth muscle the affinities of a series of 27 muscarinic receptor antagonists for M1 (rat cortex), M2 (rat heart), M3 (rat submandibular gland), m4 (transfected in CHO cells) and muscarinic binding sites in guinea-pig uterus smooth muscle were determined in radioligand binding studies. In addition, functional experiments were performed to assess pKB values of the antagonist for muscarinic receptors in guinea-pig atrium and uterus. The results obtained are consistent with the presence of M2 receptors in the uterus through which the functional contractile response is mediated. Correlation coefficients of 0.98, 0.91 and 0.91 were calculated for the following linear regressions: pKi uterus vs. pKi M2, pKB uterus vs. pKi M2 and pKB uterus vs. pKB atrium. This study also revealed that the compounds dicyclomine, DAU 5884, DAU 6202 as well as AQ-RA 721 could distinguish m4 from M2 sites and are therefore important tools to characterize muscarinic receptor subtypes. In addition, DAU 5884 and DAU 6202 have been identified as highly potent M1 selective antagonists.

Animals↗
PubMed2005

Brachytherapy management of the retroverted uterus using ultrasound-guided implant applicator placement.

PURPOSE: Patients with a retroverted uterus present a dilemma for brachytherapy in gynecologic malignancies because of the challenges of the procedure and the risk of uterine perforation. The purpose of this study was to evaluate the efficacy and outcome of ultrasound-guided brachytherapy applicator placement and intraoperative uterine anteversion in patients with gynecologic malignancies, who have a retroverted uterus. METHODS AND MATERIALS: Thirty-three brachytherapy insertions were performed in 18 patients with retroverted uterus (cervical cancer, 17; vaginal cancer, 1). The endocervical canal was dilated, the intrauterine Fletcher tandem was inserted in retroverted fashion and then anteverted along with the uterus under continuous ultrasound guidance. The anteverted tandem position was secured with vaginal packing and use of a second and/or third flange on the tandem stem. Treatment was delivered with low-dose-rate brachytherapy using afterloading with 137Cs. Brachytherapy was combined with external beam radiation in all patients. Median post-therapy follow-up was 2.17 years (range, 0.75-9.25 years). RESULTS: Procedure. Ultrasound-guided dilation of the cervix was achieved in all procedures. Sounding of the retroverted uterus up to the fundus was accomplished successfully in all but one procedure (because severe retroflexion of the uterus and fixation of the fundus to the sacrum). Ultrasound-guided anteversion of the inserted tandem and uterus was achieved in all procedures. No ultrasonographic evidence of perforation was seen in any of the procedures. Intraoperative radiographs showed satisfactory position of the applicators in 31 of the 33 procedures; 2 cases were re-packed resulting in acceptable final applicator position. No backward rotation of the tandem was observed over the duration of the low-dose-rate brachytherapy application. The mean ratio between the dose to the rectum and Point A was 73%; the ratio between the dose to the bladder and Point A was 76%. Outcome. In the 17 patients with cervical cancer, 2-year pelvic tumor control rate was 100%, and 2-year actuarial disease-free survival was 73%. The patient with vaginal cancer has no evidence of disease 5 months post-therapy. There was one complication (1/18 patients, 5.5%): a rectal stricture in a patient with stage IVA cervical cancer requiring colostomy. CONCLUSIONS: The use of ultrasound-guided uterine anteversion for brachytherapy applicator placement is feasible and results in acceptable outcome and complication rates in a population otherwise difficult to manage and at high risk for uterine perforation. Based on these results, this method is likely preferable to brachytherapy with a retroverted tandem, or to the omission of brachytherapy.

Brachytherapy↗
PubMed2005

Transfer pathways between the ovaries and the uterus in the cebus monkeys (Cebus apella).

The aim of this work was to study, in the Cebus apella monkey, the developmental changes in the microanatomy of the utero-ovarian ligament (UOL) and whether their vascular and neural elements might be involved in the transfer of signals between the ovaries and uterus. Sections including uterus, UOL, and ovary obtained from two foetuses, two prepubertal, and four cycling monkeys, two of them treated with a neuron-axonal tracer, diamidino yellow (DY) into the corpus luteum (CL) and the remaining two into the endometrium, were analyzed for the expression of neurofilament protein (NFP) and tracer distribution. Eight regularly cycling females were used to investigate the transfer to the CL of pulses of prostaglandin F(2alpha) (PGF(2alpha)) (n=4) or its vehicle (n=4) given intra-uterus. A convoluted artery, in conjunction with various vein channels, passed over the UOL allowing for a direct communication between uterus and ovaries. The artery acquired prominence during adulthood, in a manner well suited with the ovarian status. Immunohistochemical analysis revealed that NFP expression by the oocyte and by the endometrial epithelial cells was a highly conserved feature during development, whereas the appearance of NFP fibers in the ovaries, UOL, and uterus was a late event in the ontogenesis, likely regulated by the hormonal environment. Neurons, as an obvious source for these NFP fibers, were not recognized at any developmental stage, although some neuron-like cells were observed within the CL. The pattern displayed by the tracer DY, further suggested a reciprocal axonal transport among endometrial cells and follicular and luteal cells of both ovaries and between the ovaries themselves. The functionality of the utero-ovarian connection was assessed after injecting PGF(2alpha) intra-uterus. A short exposition to PGF(2alpha) pulses was required for lowering ovarian and peripheral progesterone concentrations causing luteolysis, indicating that transport mechanism operating between uterus and ovary must be very efficient. The results suggest that the vessels and axons contained in the UOL of the Capuchin monkeys might be two combined key pathways underlying the reciprocal transfer of signals controlling utero-ovarian homeostasis.

Amidines↗
PubMed1996

Laparoscopic-assisted transvaginal metroplasty for the treatment of bicornuate uterus: a case study.

OBJECTIVE: To introduce a combined laparovaginal metroplasty approach to the treatment of bicornuate uterus. DESIGN: Case report. SETTING: Private community hospital. PATIENT: A nulliparous patient with three recurrent spontaneous midtrimester abortions and a double uterus on hysterosalpingogram was evaluated laparoscopically. INTERVENTIONS: A laparoscopic-assisted transvaginal wedge metroplasty for the surgical correction of a symptomatic bicornuate uterus was performed. Intraoperative hysteroscopy also was used. MAIN OUTCOME MEASURES: Term pregnancy, uterine integrity. RESULTS: Hysteroscopic transillumination of the uterine horns delineated the uterine cavities while a laparoscopic wedge incision was initiated with a unipolar needle. The uterus was delivered through a posterior colpotomy, the wedge excision and uterine unification were completed transvaginally, the uterus was replaced into the pelvis, and the colpotomy was closed. The patient subsequently became pregnant, carried to term without complications, and delivered a healthy infant by cesarean section. The metroplasty scar was noted to be intact. CONCLUSIONS: Laparoscopic-assisted transvaginal metroplasty is a logical and useful minimally invasive alternative to laparotomy for the treatment of symptomatic bicornuate uterus and has potential utility for the treatment of complicated septate uterus and the correction of uterine perforation not amenable to laparoscopic suturing occurring during hysteroscopic septal resection.

Adult↗
PubMed1999

Disruption of estrogen signaling does not prevent progesterone action in the estrogen receptor alpha knockout mouse uterus.

Estrogen is known to increase progesterone receptor (PR) levels in the wild-type mouse uterus, and this estrogen induction was thought to be important for progesterone action through the PR. The estrogen receptor alpha knockout (ERKO) mouse uterus was observed to express PR mRNA that cannot be induced by estrogen. Progesterone action was characterized to determine whether it was diminished in ERKO mice. The PR protein is present in the ERKO uterus at 60% of the level measured in a wild-type uterus. The PR-A and PR-B isoforms are both detected on Western blot, and the ratio of isoforms is the same in both genotypes. Although the level of PR is reduced in the ERKO uterus, the receptor level is sufficient to induce genomic responses, since both calcitonin and amphiregulin mRNAs were increased after progesterone treatment. Finally, the ERKO uterus can be induced to undergo a progesterone-dependent decidual response. Surprisingly, the decidual response is estrogen independent in the ERKO, although it remains estrogen dependent in a wild type. These results indicate that estrogen receptor alpha modulation of PR levels is not necessary for expression of the PR or genomic and physiologic responses to progesterone in the ERKO uterus.

Amphiregulin↗
PubMed1959

The effect of oxytocics on the "Ca-deficient" uterus. A measure of oxytocic potency.

If the excised, parturient rabbit uterus is repeatedly treated with a Krebs solution free from Ca, its tension in a tetanus drops gradually, and in 15 to 30 minutes becomes zero. We call such a uterus "Ca-deficient." The uterus in this condition has a high threshold, it is non-propagating, "inexcitable," fails to respond to oxytocics in a characteristic fashion, but retains maximum contractility. As Ca is gradually restored to the Krebs, these lost qualities return in a graded fashion and tension of the tetanized uterus becomes a log function of the [Ca]. If the [Ca] is kept low, i.e. 1/10 to 1/20 of the normal, tetanic tension is small but steady, and the preparation offers a full scale of tension increment for the measurement of oxytocic potency. Keeping the stimulus and the [Ca] constant, excitability (measured by tension increment) is a log function of the drug concentration. The recovery of excitability by restoring Ca to the Ca-deficient uterus is strongly temperature-dependent. The Ca-deficient uterus is a useful preparation for the study of the mechanism of regulation. When its excitability is partially recovered by Ca, the electrically stimulated uterus becomes an excellent tool for the quantitative measurement of oxytocic potency.

Animals↗
PubMed1993

Estrogen regulation and localization of galanin gene expression in the rat uterus.

To determine whether galanin is a target for estrogenic regulation in the rat uterus, we measured the effects of estrogen on galanin mRNA expression in the uterus of ovariectomized rats and compared the results with the regulation of galanin in the anterior pituitary. Treatment of the animals with a single dose of 17 beta-estradiol resulted in a rapid transient increase of galanin mRNA, similar to that in the pituitary of the same animals, with a peak at 3 h after stimulation and a return to prestimulation levels after 24 h. No galanin mRNA was detected in ovariectomized control animals in either tissue. By in situ hybridization of rat uterus 3 h after estrogen stimulation, we found that galanin mRNA was localized in the endometrium in stromal cells that are close to the lumen. There was no hybridization in the myometrium of the estrogen-treated animals. Surprisingly, and strikingly different from results in the pituitary, in the uterus with a constant and prolonged exposure to estrogen by diethylstilbestrol (DES) implants, the induction of galanin mRNA was only transient, with return to baseline levels by 24 h despite the continued presence of DES. On the other hand, in the pituitary there was a rapid and sustained increase of galanin mRNA. These data demonstrate that 1) one of the initial steps in the mechanism of estrogen stimulation in the rat uterus involves galanin gene expression; 2) in the uterus galanin mRNA is expressed in stromal cells of the endometrium; and 3) the regulation of galanin mRNA expression by estrogen in the pituitary and the uterus is markedly different.

Animals↗
PubMed1998

Regulation of inducible nitric oxide synthase messenger ribonucleic acid expression in pregnant rat uterus.

Nitric oxide synthases catalyze the synthesis of the biomediator, nitric oxide, from L-arginine in a variety of tissues. The expression and regulation of inducible isoform of nitric oxide synthase (NOS II) in the uterus were assessed in this study by reverse transcription-polymerase chain reaction with the use of specific primers. Results showed the following: 1) NOS II mRNA expression in the rat uterus was substantially increased during pregnancy and decreased during labor at term; 2) RU-486 (an antagonist of progesterone) induced preterm labor and was associated with a marked decrease in NOS II mRNA expression to 60.9%, 20.3%, and 2.9% at, respectively, 6, 12, and 24 h after treatment compared with the control value (100%); 3) progesterone administration in pregnant rats significantly increased uterine NOS II gene expression (374.1% vs. 100%); 4) NOS II mRNA in the uterus was significantly reduced by prostaglandin F2alpha (PGF2alpha; 11.6% vs. 100% in control); 5) treatment with progesterone prevented PGF2alpha-induced inhibition in NOS II mRNA expression; 6) ICI 164384, an antiestrogen, significantly increased serum progesterone concentration and stimulated NOS II expression by the uterus in a time-dependent manner; 7) as shown by immunofluorescent studies, cells stained by NOS II antibodies were apparent in the decidual compartment as well as in areas between myometrial cell bundles in the pregnant rat uterus. The density of staining decreased in the specimens at labor and postpartum. We conclude that NOS II gene expression in the rat uterus was enhanced during pregnancy and decreased during labor and postpartum. NOS II in rat uterus is up-regulated by progesterone and down-regulated by estrogens and prostaglandins, consistent with their role in uterine activity regulation during pregnancy and labor.

Animals↗
PubMed2006

Auto-transplantation of the uterus in the domestic pig (Sus scrofa): Surgical technique and early reperfusion events.

AIM: To develop a method for auto-transplantation of the uterus in the pig and to evaluate the early reperfusion events after short-term cold ischemia. METHODS: The bicornate uterus, with the cervix but without ovaries, was dissected and isolated with its bilateral feeding and draining vessels. The uterine arteries were cannulated in situ and the uterus was flushed with heparinized Ringer Acetate. It was stored at 4 degrees C for 1-2 h during continuous flushing. The uterus was then placed in its original pelvic position and the uterine arteries and veins were anastomosed end-to-end to their origin. During approximately 100 min of reperfusion, blood samples and tissue biopsies were taken for monitoring of reperfusion events and detection of ischemia-reperfusion injuries. RESULTS: Out of 19 auto-transplanted pigs, seven were considered well flushed and were kept for cold ischemia. Of these seven, four showed satisfactory reperfusion judged by change in gross appearance and presence of appropriate venous blood flow. Analysis of blood-gas and metabolite parameters and histology indicated that at least two of these transplants were well reperfused, with no severe ischemia-reperfusion injuries. CONCLUSION: In this first report ever on auto-transplantation of the pig uterus it is demonstrated that an acceptable reperfusion can be achieved. Furthermore, it is suggested that because of the large total size of the pig uterus with long uterine horns and the small size of the vessels available for re-anastomosis, the pig is a fairly difficult model for further studies on transplantation of the uterus.

Animals↗
PubMed1986

The beta 1- and beta 2-adrenoceptor stimulatory effects of alprenolol, oxprenolol and pindolol: a study in the isolated right atrium and uterus of the rat.

The rat isolated right atrium (frequency response) and progesterone-treated rat uterus (relaxation) were used to examine the beta 1- and beta 2-adrenoceptor stimulatory effects of alprenolol, oxprenolol and pindolol. In addition, the beta 1-adrenoceptor stimulatory effect of practolol was studied in the right atrium. All the compounds studied caused a concentration-dependent increase in atrial frequency and relaxation of the uterus. The atrial response to pindolol was competitively inhibited by the beta 1-selective blocker pafenolol (10(-7) M), while the beta 2-selective blocker ICI 118551 (10(-8) M) was without effect. Pafenolol (10(-7) M) was also shown to inhibit the atrial frequency effect of alprenolol and oxprenolol. In the uterus, ICI 118551 (3 X 10(-9) M, 3 X 10(-8) M, 3 X 10(-7) M) blocked the pindolol effect with a pKB of 9.28. In addition, ICI 118551 (10(-8) M) competitively inhibited the relaxation of the uterus induced by alprenolol and oxprenolol. For alprenolol (right atrium and uterus), oxprenolol (right atrium), and pindolol (right atrium), the concentrations needed for half-maximal response were significantly greater than those required for occupation of half the receptors. This dissociation was most pronounced for pindolol in the right atrium. In this tissue, 80-85% of the beta 1-adrenoceptors had to be occupied by pindolol to initiate a tissue response corresponding to 50% of the maximal effect generated by the compound. The intrinsic activities of alprenolol, oxprenolol and pindolol (expressed as % of the maximal tissue response to isoprenaline) were significantly higher in the uterus than in the right atrium. The intrinsic activity of the compounds varied between individual preparations and, particularly in the uterus, correlated with the sensitivity of the tissue to beta-adrenoceptor stimulation by isoprenaline. 5 Calculation ofefficacy, relative to isoprenaline, of the partial beta-agonists revealed a beta 2-adrenoceptor selectivity for alprenolol (2.0), oxprenolol (1.4) and pindolol (3.0). 6 It is concluded that weak partial agonists such as alprenolol, oxprenolol and pindolol possess complex beta 1- and beta 2-adrenoceptor stimulatory properties in relation to beta-adrenoceptor occupancy and tissue sensitivity to beta-adrenoceptor stimulation.

Adrenergic beta-Agonists↗
PubMed1994

Progesterone stimulates calcitonin gene expression in the uterus during implantation.

Implantation of the mammalian embryo into the wall of the uterus is regulated by a timely interplay of the ovarian hormones, estrogen and progesterone. These hormones orchestrate a set of modifications in the uterine endometrium that transforms it from a nonreceptive to a receptive phase allowing the implantation of the developing blastocyst. The molecular and cellular mechanisms underlying this complex process, however, remain largely unknown. To investigate the endocrine basis of uterine receptivity, we employed a gene expression screen technique to identify factors whose expressions are modulated in the rat uterus in response to estrogen and progesterone at the onset of implantation. Here we report that the expression of calcitonin, a peptide hormone involved in calcium homeostasis, is markedly enhanced in the uterus during pregnancy. By Northern blot analysis, we show that the synthesis of calcitonin messenger RNA is induced at the time of implantation. Immunocytochemistry with calcitonin antibody demonstrates further that the peptide is localized in the glandular epithelial cells of the uterus. The antiprogestin drug RU486, which is known to block implantation, abolishes calcitonin expression, suggesting a regulatory role for progesterone in this process. Consistent with this observation, progesterone significantly stimulates calcitonin messenger RNA and protein synthesis in the uteri of ovariectomized animals. Our study, therefore, identifies calcitonin as a stage- and cell-specific marker of progesterone action in the uterus during pregnancy. Estrogen exhibits no significant effect on calcitonin expression when administered alone to ovariectomized animals. However, a low dose of estrogen synergizes with progesterone, and a high dose antagonizes progesterone-mediated gene induction. Both estrogen and progesterone, therefore, modulate calcitonin gene expression in the uterus. The stage-specific regulation of calcitonin is apparently determined by the relative concentrations and the sequences of appearance of these two hormones and possibly other as yet unknown regulatory factors during pregnancy. We propose that calcitonin, a known regulator of calcium levels in the bone and kidney, may play an important regulatory role in the uterus of pregnant animals during the early events leading to implantation of the embryo.

Animals↗
PubMed1997

Expression of adrenomedullin (ADM) and its binding sites in the rat uterus: increased number of binding sites and ADM messenger ribonucleic acid in 20-day pregnant rats compared with nonpregnant rats.

RIA of nonpregnant rat uterus extracts showed 0.68 +/- 0.08 pmol/g adrenomedullin (ADM) and 3.23 +/- 0.08 pmol/g calcitonin gene-related peptide (CGRP). In the pregnant (20 days gestation) uterus, the ADM content was 0.90 +/- 0.17 pmol/g, and CGRP could not be detected. ADM messenger RNA was detected at high levels in the uterus, with a 1.8-fold increase in expression in pregnancy. Pharmacologically distinct binding sites for ADM (Bmax = 21 +/- 2 fmol/mg protein, dissociation constant = 80 +/- 6 pM), and CGRP (Bmax = 101 +/- 18 fmol/mg protein, dissociation constant = 140 +/- 20 pM) were identified in nonpregnant uterus. Competition for 125I[Tyr0]alphaCGRP binding was shown by both ADM and CGRP (8-37), whereas CGRP and CGRP (8-37) did not compete for 125I-ADM-binding sites. The density of the ADM-binding sites was 10 times greater in pregnant uterus (Bmax = 211 +/- 39 fmol/mg protein, P < 0.01) than nonpregnant uterus. CGRP receptor messenger RNA was identified in both nonpregnant and pregnant uteri. In isolated nonpregnant rat uteri, CGRP and ADM attenuated the contractile response to galanin by 77 +/- 10% and 57 +/- 10%, respectively. The responses to both CGRP and ADM were abolished by CGRP (8-37). These results demonstrate, for the first time, the presence of ADM and specific binding sites for both ADM and CGRP in the rat uterus.

Adrenomedullin↗
PubMed2005

Chromatin immunoprecipitation analysis of gene expression in the rat uterus in vivo: estrogen-induced recruitment of both estrogen receptor alpha and hypoxia-inducible factor 1 to the vascular endothelial growth factor promoter.

Vascular endothelial growth factor (VEGF) plays a pivotal role in the regulation of microvascular permeability and angiogenesis, processes essential for normal endometrial growth and implantation. Estrogen [17beta-estradiol (E2)], via its receptor (ER alpha), rapidly stimulates VEGF expression in the uterus at the transcriptional level. The VEGF gene promoter, however, lacks a consensus estrogen response element (ERE), and attempts to identify the site through which E2 induces VEGF expression have yielded contradictory results. To address this question, we modified the chromatin immunoprecipitation method to identify transcription factors that interact with the VEGF promoter in the rat uterus in response to E2. Chromatin immunoprecipitation showed that both Sp1 and Sp3 were associated with a proximal, GC-rich region of the promoter before E2 treatment. E2 induced an increase in Sp1 binding and the recruitment of ER alpha, and the coactivator p300 to this region. The association of ER alpha persisted, however, after VEGF mRNA levels had declined again (at 4 h), indicating that other factors might be involved in that expression. Western analysis showed that both the alpha- and beta-subunits of the transcription factor hypoxia-inducible factor 1 (HIF-1), which regulates VEGF expression in response to hypoxia and several hormones and growth factors, were present in the uterus. Furthermore, E2 rapidly induced their recruitment to the -944 to -611 bp region of the VEGF promoter, which contains the hypoxia response element to which HIF-1 binds. This binding was transient, matching the pattern of E2-induced VEGF expression. These results indicate that HIF-1 is an important mediator of E2-induced VEGF expression in the uterus. In addition, E2 also induced a later increase in HIF-1alpha mRNA and protein expression in the uterus, suggesting that it may be required for longer term effects of E2 on the uterus as well. In contrast to the uterus, HEC1A cells cultured in 95% air-5% CO2 (and therefore 20% O2) contained no HIF-1alpha, consistent with the inability of E2 to stimulate the expression of VEGF by these and other cell types in vitro.

Animals↗
PubMed1995

Amphiregulin is an implantation-specific and progesterone-regulated gene in the mouse uterus.

A synchrony between the activated state of the blastocyst and differentiation of the uterus to the receptive state is essential to the process of implantation. This process is directed by progesterone (P4) and estrogen. The mechanism by which P4 differentiates the uterus, enabling estrogen to initiate implantation, is unknown but likely to involve localized induction of growth and differentiation factors. We have cloned the murine amphiregulin (AR) gene, a newly discovered member of the epidermal growth factor family, and demonstrate that its expression is implantation-specific and P4-regulated in the mouse uterus. A transient surge in AR mRNA levels occurred throughout the uterine epithelium on day 4 of pregnancy. With the onset of blastocyst attachment late on day 4, AR mRNA accumulated in the luminal epithelium exclusively at the sites of blastocysts. Thus, AR expression correlated first with rising P4 levels and then with the attachment reaction. The rapid induction of AR mRNA in the ovariectomized uterus only by P4 and abrogation of this induction by RU-486 (a P4 receptor antagonist) suggest that this uterine gene is regulated by P4. AR appeared to exhibit preferential phosphorylation of epidermal growth factor receptor in the uterus over that in the blastocyst. This is a first report of a P4-regulated uterine epithelial cell growth factor that is associated with epithelial cell differentiation during implantation. The association of AR in implantation is further documented by its down-regulation in the day 4 pregnant uterus in which uterine receptivity and implantation were disrupted by estrogen or RU-486 treatment on day 3. These results further indicate that the expression of the AR gene could serve as a molecular marker for the receptive state of the uterus for implantation.

Amino Acid Sequence↗
PubMed1985

Effect of trifluoperazine, a calmodulin antagonist, on prostaglandin output from the guinea-pig uterus.

Trifluoperazine, a calmodulin antagonist, inhibited the A23187-induced increase in outputs of prostaglandin (PG) F-2 alpha and 6-oxo-PGF-1 alpha from the Day 7 and Day 15 guinea-pig uterus superfused in vitro. The basal outputs of, and the arachidonic acid-induced increase in outputs of PGF-2 alpha, PGE-2 and 6-oxo-PGF-1 alpha from the guinea-pig uterus were not inhibited by trifluoperazine. In contrast, indomethacin inhibited A23187-stimulated, arachidonic acid-stimulated and the basal outputs of PGs from the guinea-pig uterus, indicating that trifluoperazine was not inhibiting cyclo-oxygenase. Since the action of A23187 is dependent upon extracellular Ca2+, the present findings provide evidence that calmodulin is involved in Ca2+-induced increases in uterine PG output from the guinea-pig uterus. Trifluoperazine, but not indomethacin, inhibited A23187-induced contraction of the guinea-pig uterus, which is consistent with calmodulin being involved in smooth muscle contraction. Arachidonic acid treatment did not contract the guinea-pig uterus. These findings indicate that PGs are not involved in the contraction induced by A23187. Other findings of interest were (i) trifluoperazine caused a small, sometimes significant (P less than 0.05), increase in uterine PG output, (ii) exogenous arachidonic acid failed to increase PGF-2 alpha output from the Day 15 uterus in contrast to the stimulant action of A23187, and (iii) exogenous arachidonic acid caused a fairly large increase in uterine PGE-2 output in contrast to the small effect with A23187.

6-Ketoprostaglandin F1 alpha↗
PubMed1995

Effect of ovarian steroid hormones and the presence of the fetus on oxytocin gene expression in the uterus.

Oxytocin (OT) is a neurohypophysial hormone with potent stimulating activity of the pregnant uterus, but its physiological role in parturition is still unclear. Recently, OT was found to be synthesized in the pregnant uterus, indicating that OT originating from the uterus, not from the posterior pituitary gland, may trigger the onset of labour. In order to define the factors responsible for the induction of uterine OT, the effect of ovarian steroid hormones and conceptus on the induction of OT mRNA in the rat uterus was examined by Northern and dot blot hybridization analysis. OT mRNA in the uterus started to increase on day 14 of pregnancy and showed very high levels at the time of parturition. Uterine OT mRNA was not altered by any steroid treatment, oestradiol-17 beta (0.2 microgram), progesterone (4 mg) or both in combination, for 6 days. The gravid horn of the uterus had 3.6-fold as much OT mRNA as the non-gravid horn on day 21 of pregnancy in hemipregnant rats with one ligated oviduct. The ovarian steroid hormones could not induce accumulation of OT mRNA in the uterus of ovariectomized rats, at least under the conditions used, but the presence of a conceptus may be critical for the very high levels of OT mRNA.

Animals↗
PubMed1990

[Biometric parameters of the uterus, ovaries and levels of 17 beta-estradiol (E2) after delivery in sheep].

Biometric changes of uterus, ovaries, follicles and 17 beta-oestradiol (E2) concentrations were investigated in 15 lambing ewes of the Slovak Merino breed in the puerperal period. The sex organs were excised immediately after bleeding from ewes slaughtered on days 1, 7, 17, 25 and 34 post partum (p. p.). Biometric parameters of the body and horns of uterus were measured by a calliper. The ovaries were weighed on an analytical balance, their length, width and height were measured at the same time. The size and number of follicles were determined on the ovary surface. The blood for E2 detection was collected from vena jugularis three and one day before delivery (days -1, -3). Blood samples were also collected after delivery on days 1, 7, 17, 25 and 34. E2 concentrations in the blood serum of ewes were determined by RIA-test-ESTRA kits, designed in one institute at Kosice. The highest weight of uterus body in the test ewes was recorded on day 1 p. p. In the following days the weight of uterus body had a decreasing trend. There were significant differences in the weight of uterus body from day 17 to day 34 p. p., in comparison with the first day after lambing (P less than 0.01). A significant decrease in the length of uterus body was observed from day 17 to day 34 of observation (P less than 0.01; P less than 0.001). An increase in the length of a nongravid horn, observed on day 7 p. p., was followed by a gradual decrease until day 34, similarly like in its weight. No statistically significant differences were found out in the ovary length, width and height. Neither were any greater changes recorded in the weight of ovaries from day 1 to day 34 after delivery. The highest number of small structures (28) observed on day 7 p. p. in the ipsilateral ovary was decreasing in the course of puerperium and the number of follicles larger than 2, 4 and 5 mm was increasing. The highest concentrations of E2 were not recorded on day -1 before delivery. The significantly lowest concentrations of E2 were recorded on day 25 p. p. The above-mentioned results are preliminary and they enlarge the knowledge of biometric parameters of uterus, ovaries, follicles and E2 concentrations after delivery in ewes.

Animals↗
PubMed1985

The gelatinolytic activity of rat uterus collagenase.

The collagenase produced by rat uterine cells in culture has been examined for its ability to degrade denatured collagen. Acting as a gelatinase, rat uterus collagenase was able to successfully degrade the denatured chains of collagen types I through V. In addition, the enzyme produced multiple cleavages in these chains and displayed values for Km of 4-5 microM, compared to values of 1-2 microM when native collagen was used as substrate. Furthermore, rat uterus collagenase degraded the alpha 2 chain of denatured type I collagen at a significantly faster rate than the alpha 1 chain, as previously observed for human skin fibroblast collagenase. In contrast to the action of human skin collagenase, however, the rat uterus enzyme was found to be a markedly better gelatinase than a collagenase, degrading the alpha chains of denatured type I guinea pig skin collagen at rates some 7-15-fold greater than native collagen. Human skin collagenase degrades the same denatured chains at rates ranging from 13-44% of its rate on native collagen. Rat uterus collagenase, then, is approximately 50 times better a gelatinase than is human skin collagenase. In addition to its ability to cleave denatured collagen chains at greater rates than native collagen, the rat uterus collagenase also attacked a wider spectrum of peptide bonds in gelatin than does human skin collagenase. In addition to cleaving the Gly-Leu and Gly-Ile bonds characteristic of its action on native collagen, rat uterus collagenase readily catalyzed the cleavage of Gly-Phe bonds in gelatin. The rat enzyme was also capable of cleaving Gly-Ala and Gly-Val bonds, although these bonds were somewhat less preferred by the enzyme. The cleavage of peptide bonds other than Gly-Leu and Gly-Ile appears to be a property of the collagenase itself and not a contaminating protease. Thus, it appears that the collagenase responsible for the degradation of collagen during the massive involution of the uterus might also act as a gelatinase to further degrade the initial products of collagenolysis to small peptides suitable for further metabolism.

Amino Acid Sequence↗