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PubMed1983

Plasminogen activators in tissues of the immature and estrogen-stimulated rat uterus and in uterine luminal fluid: characterization and properties.

We have characterized the molecular properties of the plasminogen activators in different cell types comprising the immature and the estrogen-stimulated rat uterus and in rat uterine luminal fluid. There were two plasminogen activators in the immature (day 20) rat uterus with apparent molecular weights, determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, of 70,000 and 46,000. Both plasminogen activators were present in epithelial and in stromal plus myometrial cell fractions of the immature uterus, and after stimulation by 17 beta-estradiol, no new plasminogen activators were detected in either cell fraction. The Michaelis constants (Km) for the activation of dog plasminogen by extracts from epithelial cells and from stromal plus myometrial cells obtained from either immature or 17 beta-estradiol-stimulated uteri were similar (approximately 11 microM). The maximal velocity (Vmax), normalized to protein concentration, increased 2.5-fold in the stromal plus myometrial cell fraction and 6.5-fold in the epithelial cell fraction, upon hormone stimulation (2 micrograms 17 beta-estradiol/day X rat for 3 days). The greatest concentration of plasminogen activator activity was found in the luminal fluid from estrogen-stimulated uteri, where the Vmax per mg protein was more than 10-fold greater than that in the cell fractions from estrogen-stimulated uteri. The plasminogen activator activity of luminal fluid was inhibited by diisopropyl fluorophosphate and rho-nitrophenyl rho-guanidinobenzoate, was not inhibited by human alpha-1-proteinase inhibitor and human antithrombin III, and was inhibited by high, but not low, concentrations of soybean trypsin inhibitor and bovine pancreatic trypsin inhibitor. These studies indicate that the plasminogen activators in different cell types comprising the uterus are similar and show that the estrogen enhancement of uterine plasminogen activator activity is the result of an increase in Vmax. The presence, upon hormone stimulation, of an apparent concentration gradient of increasing plasminogen activator activity through the uterus from myometrium to epithelium to luminal fluid may be a reflection of the dynamic role of this protease in the physiology of the uterus.

Animals↗
PubMed1983

Estrogenic stimulation of the antiestrogen specific binding site in rat uterus and liver.

Tamoxifen and other antiestrogens bind to the estrogen receptor and to a specific antiestrogen binding site (AEBS). We have confirmed the existence of an AEBS by saturation and competitive binding analyses with [3H]tamoxifen as the radiolabeled ligand. The quantities of AEBS (pmol/g tissue) present in a low speed cytosol (25,000 X g X 30 min) of the liver and uterus vary with species and physiological state: liver, mature female rat, 82.7 +/- 6.7; ovariectomized mature rat, 46.1 +/- 2.9; immature female rat, 40.0 +/- 1.8; mature male rat, 57.3 +/- 2.7; and mature female mouse, 63.0 +/- 5.0; uterus, mature rat, 17.9 +/- 1.7; ovariectomized mature rat, 13.3 +/- 0.5; immature rat, 8.2 +/- 0.8; and mature mouse, 49.0 +/- 2.1. The dissociation constants did not differ significantly in any of the cases and were 1.5 and 2.5 nM for the liver and uterus, respectively. Developmental studies demonstrated that the liver AEBS gradually increases in both sexes from 21.0 pmol/g at birth to their respective adult levels with the only divergence occurring approximately at the time of puberty. The AEBS concentration also varied with the stage of the estrous cycle [highest at estrus (20.6 +/- 1.8) and metestrus (91.7 +/- 5.9) for the uterus and liver, respectively, and lowest at diestrus (uterus, 15.9 +/- 0.2; liver, 60.2 +/- 4.1)]. Furthermore, estradiol treatment of ovariectomized rats significantly increased both liver and uterine AEBS levels, whereas tamoxifen increased uterine AEBS concentration although having no significant effect on the level of these sites in liver. These results demonstrate the presence of a cytosolic AEBS in the liver and uterus which is distinct from the estrogen receptor and appears to be under estrogenic regulation.

Animals↗
PubMed1990

Estrogen regulation of a tissue factor-like procoagulant in the immature rat uterus.

An estrogen-responsive procoagulant activity is present in the plasma membrane fraction of immature rat uterus. This procoagulant has many of the properties of tissue factor, a widely occurring, integral membrane protein which initiates the intrinsic pathway of coagulation. Procoagulant activity was demonstrated to activate prothrombin in rat uterus, to activate human coagulation factor X, and to cause clot formation by human plasma. Procoagulant activity could be solubilized from the plasma membrane by the detergent octyl glucoside and had an apparent mol wt of 20,000-40,000 by gel filtration. Procoagulant activity was increased 4-fold within 3 h after immature rats were injected with estradiol. The increase was tissue- and hormone specific and was not affected by a warfarin-induced vitamin K deficiency. Coagulation factor VII was required for clot formation by the procoagulant. These properties are consistent with identification of the procoagulant as tissue factor. mRNA for tissue factor was increased in the uterus 3 h after estrogen stimulation. In the preceding paper we showed that prothrombin is increased in the immature uterus within 3 h of estrogen stimulation. The presence of increased amounts of a tissue factor-like procoagulant in the same time period suggests a functional relationship between these two proteins and a possible role for both in uterine development. Thrombin is a growth factor in fibroblasts and endothelial cells. We propose that after estrogen stimulation, prothrombin enters the uterus with the influx of plasma proteins and is activated by the procoagulant to thrombin. We suggest that thrombin might act as a paracrine factor early in the estrogen-stimulated development of the uterus.

Animals↗
PubMed1991

In vivo regulation of parathyroid hormone-related peptide messenger ribonucleic acid in the rat uterus by 17 beta-estradiol.

During pregnancy, elevated levels of PTH-related peptide (PTHrP) persist in the myometrium of the rat uterus. Near term, intrauterine occupancy is correlated with high levels of PTHrP messenger RNA in the gravid horn of the unilaterally pregnant uterus. In nongravid tissue from these same animals the presence of smaller yet significant elevations of PTHrP mRNA suggests that the PTHrP gene also may be regulated by humoral factor(s). To test this hypothesis, we assessed the action of 17 beta-estradiol (E2) on the expression of the PTHrP gene in the uterus of the ovariectomized rat. While low levels of PTHrP mRNA are detected in uteri from ovariectomized rats, a single dose of E2 (4, 40, or 400 micrograms/kg body weight) stimulated a 6- to 8-fold increase in the levels of PTHrP mRNA in the uterus at approximately 2 h after E2 treatment. This increase was transient with levels gradually declining to pretreatment (basal) levels within 24 h. Other steroid hormones tested, including dihydrotestosterone, dexamethasone, and progesterone, failed to stimulate this response. The increase of PTHrP mRNA accumulation required a dose greater than 0.4 micrograms/kg. The magnitude and duration of PTHrP mRNA accumulation were very similar when doses of 40 or 400 micrograms/kg were used. In addition, the stimulation of the PTHrP gene by E2 is neither age dependent nor specific to the rat and is, in part, under transcriptional control. Together, these data indicate that in vivo E2 regulates the levels of PTHrP mRNA in the rat uterus and support a role for E2 in the increased expression of PTHrP mRNA in early gestational tissue, as well as in the nongravid horn of the unilaterally pregnant uterus.

Aging↗
PubMed1994

Gastrin-releasing peptide is produced in the pregnant ovine uterus.

Our previous finding of appreciable quantities of a gastrin-releasing peptide (GRP)-like immunoreactive (GRPLI) entity in ovine fetal and maternal plasma led us to examine the ovine pregnant uterus as a possible source of this material. At term, intense immunohistochemical staining for GRPLI occurred in the endometrial epithelial cells, and the term ovine uterus also contained abundant GRP messenger RNA (mRNA). In contrast, GRP mRNA was not detected in fetal membranes. GRP mRNA was present in the uterus on gestational day 63; a significant increase in GRP mRNA had occurred by day 100. Thereafter, levels remained elevated until term, but 3 months postpartum, GRP mRNA levels were greatly reduced. As previous studies suggested the GRPLI entity to be of greater molecular size than GRP-(1-27), we deduced the primary structure of ovine uterus GRP by sequencing a complementary DNA clone isolated from a complementary DNA library constructed from term ovine uterus polyadenylated RNA. Ovine uterine GRP is composed of 27 amino acid residues and has a conserved C-terminal region, similar to GRP structures in other species. We conclude that during pregnancy, the ovine uterus produces considerable quantities of GRP, which may play an important but hitherto unrecognized role in utero-placental development and possibly in fetal development after transfer to the fetus.

Amino Acid Sequence↗
PubMed1996

Regulation and localization of cellular retinol-binding protein, retinol-binding protein, cellular retinoic acid-binding protein (CRABP), and CRABP II in the uterus of the pseudopregnant rat.

Three members of the superfamily of small intracellular carrier proteins for lipophilic compounds are cellular retinol-binding protein (CRBP), cellular retinoic acid-binding protein (CRABP), and cellular retinoic acid-binding protein II (CRABP II). Retinol-binding protein (RBP) is a secreted protein that binds and solubilizes vitamin A for transport. Here we report the coordinate regulation of RBP, CRBP, retinol, and CRABP II in the uterus of the pseudopregnant rat. In the proliferative stage of the uterus, which was induced by PMSG, the messenger RNA (mRNA) and protein levels of RBP and CRBP as well as retinol levels significantly decreased. This pattern of regulation was duplicated by estrogen treatment of prepubertal rats. In addition, CRBP and RBP were found to be colocalized to the stromal cells of the rat uterus by immunohistochemistry and [35S]methionine-labeled affinity chromatography, respectively, and were not detected in other cell populations. CRABP II mRNA and protein expression were up-regulated in the proliferative phase of the uterus brought about by PMSG injection or, alternatively, by estrogen treatment of prepubertal rats. CRABP II was localized to the surface epithelium, but was not seen elsewhere, including glandular epithelium. Immunolocalization of CRABP showed staining of the smooth muscle and stromal cells of the uterus. The appearance of CRABP in the stroma of the uterus also correlated with PMSG injection as well as estrogen treatment. Although estrogen induced the appearance of both binding proteins, CRABP mRNA levels peaked between 4-24 h postestrogen treatment, whereas CRABP II mRNA levels continued to rise 48 h postestrogen treatment. These data demonstrate an important role for vitamin A and retinoid-binding proteins in rat uterine physiology.

Animals↗
PubMed2000

Trophinin expression in the mouse uterus coincides with implantation and is hormonally regulated but not induced by implanting blastocysts.

Trophinin mediates apical cell adhesion between two human cell lines, trophoblastic teratocarcinoma and endometrial adenocarcinoma. In humans, trophinin is specifically expressed in cells involved in implantation and early placentation. The present study was undertaken to establish trophinin expression by the mouse uterus. In the pregnant mouse uterus, trophinin transcripts are expressed during the time which coincides with the timing of blastocyst implantation. Trophinin is also expressed in the nonpregnant mouse uterus at estrus stage. Uteri from ovariectomized mice did not express trophinin, whereas strong expression was induced by estrogen but not by progesterone. Trophinin transcripts and protein were found in the pseudopregnant mouse uterus. No differences were detected in trophinin expression by the uteri in the pregnant, pseudopregnant, and pseudopregnant received blastocysts. In delayed implantation model, trophinin proteins were found in both luminal and glandular epithelium, whereas dormant blastocysts were negative for trophinin. Upon activation with estrogen, however, no significant changes were detected either in the blastocyst or in the uterus. These results indicate that ovarian hormones regulate trophinin expression by the mouse uterus, and that an implanting blastocyst has no effect on trophinin expression in the surrounding endometrial luminal epithelial cells.

Animals↗
PubMed2000

Localization and signaling of the prolactin receptor in the uterus of the common marmoset monkey.

This study investigated the expression and signaling pathway of PRL and its receptor in the non-pregnant uterus of the common marmoset monkey. Immunohistochemistry localized PRL expression to the stromal compartment of the endometrium. Expression was minimal during the proliferative phase and was up-regulated during the mid to late secretory phase of the ovulatory cycle. In situ hybridization and immunohistochemistry localized expression of the PRL receptor to the glandular epithelium of the endometrium. Similar to that of PRL, PRL receptor expression was minimal during the proliferative phase and was dramatically up-regulated during the secretory phase. The temporal pattern of PRL receptor gene expression in the marmoset uterus across the cycle was further confirmed by ribonuclease protection assay. The roles of Janus kinase-2 (JAK2) and signal transducer and activator of transcription-1 (STAT1) in the intracellular signaling pathway of PRL were also assessed in the mid to late secretory phase. JAK2/STAT1 proteins were localized in the glandular epithelial compartment, and both proteins were temporally phosphorylated in response to PRL. Finally, the pattern of expression of the interferon regulatory factor-1 (IRF-1) gene and the effect of PRL on transcription of IRF-1 were investigated during the mid to late secretory phase. IRF-1 expression in the marmoset uterus was encoded by a protein of 48 kDa and was localized to the glandular epithelial compartment, as was observed for the PRL receptor and JAK2/STAT1 proteins. Moreover, incubation of mid to late secretory uterine tissue with PRL for 1 and 3 h resulted in 0.4 +/- 0.2- and 2.4 +/-0.5-fold (P < 0.05) inductions of the IRF-1 gene, respectively. These studies confirm the expression of both PRL and its receptor in the uterus of the marmoset monkey. Expression of both genes is up-regulated during the mid to late secretory phase of the ovulatory cycle. PRL function in the marmoset uterus is linked to the JAK/STAT signaling pathway, leading to the regulation of expression of PRL-responsive genes such as IRF-1. The site of expression of PRL, PRL receptors, and IRF-1 in the marmoset uterus suggest that PRL may influence glandular epithelial function and direct gene transcription in these cells in a paracrine fashion.

Animals↗
PubMed2004

Differential transcriptional and translational regulations of calbindin-D9k by steroid hormones and their receptors in the uterus of immature mice.

Calbindin-D(9k) (CaBP-9k) is a cytosolic calcium binding protein mainly expressed in the duodenum, placenta and uterus, and intestinal CaBP-9k is regulated by 1, 25-dyhydroxyvitamin D3. However, despite the presence of vitamin D receptors, uterine CaBP-9k is not under the control of vitamin D, but seems to be regulated by sex steroids. This steroids-dependent regulation of CaBP-9k is not only limited to a tissue-specific manner but also extends to a species-specific manner. In this study, we examined the regulation of CaBP-9k gene at the transcriptional and translational levels, and also localized CaBP-9k protein in the uterus of immature mice. Treatment with progesterone (P4) resulted in the induction of CaBP-9k mRNA, and a co-treatment with estrogen (E2) plus P4 evoked a synergic effect on its mRNA level in this tissue. Interestingly, the translation of CaBP-9k protein was enhanced by E2, while no difference was observed at the transcriptional level. Not only P4 but also E2 itself induced an increase of CaBP-9k protein, and co-treatment with E2 and P4 showed a similar effect on its protein level in the uterus of immature mice. The CaBP-9k protein was localized in the glandular epithelium of stroma in the uterus of immature mice at diestrus, indicating that the expression of CaBP-9k protein is differentially regulated by sex steroids. A potential mechanism of synergic effect of P4 and E2 may be E2 action in the increase of progesterone receptor (PR), with up-regulated PR increasing P4-induced CaBP-9k expression. This complicated relationship between CaBP-9k and steroid receptors suggests that P4 regulates CaBP-9k gene in the uterus of immature mice, in addition, E2 also can affect the expression of CaBP-9k through the regulation of PR. The expression levels of ERalpha and PR were further examined in this tissue. E2 stimulated the expression levels of ERalpha and PR mRNAs and P4 inhibited the expression of these transcripts at an early time point (12 h) and increased them at 24 and 48 h, while co-treatments with both steroids increased transcripts of ERalpha and PR at 24 h. In conclusion, P4 and PR may be dominant factors in the regulation of CaBP-9k. Also, E2 and ERalpha can influence the expression of the CaBP-9k gene via an indirect pathway in the uterus of immature mice.

Age Factors↗
PubMed1992

Hormonal modulation of prolyl endopeptidase and dipeptidyl peptidase IV activities in the mouse uterus and ovary.

Prolyl endopeptidase and dipeptidyl peptidase IV are proline-specific peptidases, and are ubiquitously distributed in various tissues in mammals. The specific activities of these peptidases in both uterus and ovary were examined in the SHN strain of mice at estrus or diestrus. A marked change in prolyl endopeptidase activity was found in the uterus and ovary in intact mice during the estrous cycle, the activity being high at estrus and low at diestrus. In ovariectomized mice, prolyl endopeptidase activity was significantly higher in the uterus treated with progesterone or estradiol than in the uterus treated with vehicle oil only or a dopamine antagonist (perphenazine) which stimulates prolactin secretion. On the other hand, notable change in dipeptidyl peptidase IV activity during the estrous cycle was found only in the uterus of intact mice. The activity was low at estrus and high at diestrus. In ovariectomized mice, the uterus exposed to estradiol showed a lower dipeptidyl peptidase IV activity than the uteri treated with progesterone, the dopamine antagonist or vehicle oil. These findings reveal that there is a close correlation between the circulating level of ovarian steroids and the activities of these proline-specific enzymes.

Animals↗
PubMed1979

Influence of hCG injection and steroid treatment on prostaglandin metabolism by rabbit uterus and oviduct.

Metabolism of PGE-2 and PGF-2 alpha by cytosolic fractions (100 000 g supernatant) of rabbit uterus, oviduct and lung was measured in vitro. Metabolism of PGE-2 was greater than that of PGF-2 alpha for oviduct and uterus. After an ovulating injection of hCG metabolism of both PGE-2 and PGF-2 alpha by lung and uterus declined linearly up to 72 h (during the time of ovum transport). The amount of PG metabolism by the oviduct did not change significantly during this period, but the percentage changes of PGE-2 and PGF-2 alpha metabolism from oestrous values did differ, and perhaps indicated a change in the ratio of intracellular PGs. No change of metabolism of either PG by lung, uterus or oviduct occurred at 24 or 72 h after an injection of 250 micrograms oestradiol cyclopentylpropionate given concomitantly with the hCG (a treatment regimen which causes 'tube-locking' of ova). However, progesterone treatment, in a regimen known to cause accelerated transport of ova through the oviduct, caused significantly enhanced metabolism of both PGE-2 and PGF-2 alpha by uterus and oviduct, but not lung, 30 and 48 h later except for PGE-2 by uterus at 30 h. These results suggest that changes in metabolism of PGE-2 and PGF-2 alpha by the oviduct may be involved in the mechanisms controlling ovum transport.

Animals↗
PubMed1980

Prostaglandin and thromboxane production by the rat uterus and ovary in vitro during the oestrous cycle.

The major prostaglandin (PG) synthesized by homogenates of the rat uterus and ovary in vitro was prostacyclin (PGI-2), has reflected by the amounts of 6-oxo-PGF-1 alpha produced. Thromboxane production by both tissues was low, whereas appreciable quantities of PGF-2 alpha, PGE-2 and PGD-2 were produced. Prostaglandin production by the uterus was higher on Day 1 (oestrus) than on Day 3 (dioestrus), although the ratio of the amounts of the PGs formed remained fairly constant for each day. There was no daily variation in the amounts of PGs synthesized by the ovary. Metabolism of PGF-2 alpha by the rat uterus and ovaries was generally low, although the ovaries had a higher metabolizing capacity than the uterus. Metabolism by the uterus was higher on Day 1 than on Day 3 of the cycle. The decreased production of PG by the uterus on Day 3 is therefore not due to increased metabolism.

Animals↗
PubMed1990

Embryo implantation associated with increase in T-cell suppressor factor in the uterus and spleen of mice.

The concentrations of T-cell suppressor factor (TsF) were examined by competitive binding assays in the uterus, spleen, and regional lymph nodes draining the uterus in Day-5 pregnant mice or in ovariectomized mice given hormone treatments to induce conditions of delayed implantation or implantation. The amounts of immunoreactive TsF on Day 5 of pregnancy were 2.055 +/- 0.302, 0.803 +/- 0.088, 0.426 +/- 0.136 ng TsF/mg extractable protein for the regional lymph nodes, spleen and uterus, respectively, during Day 5 of pregnancy. When implantation was prevented by ovariectomy on Day 4 followed by treatment with only progesterone, amounts of TsF (as a % of Day 5 value) were decreased to 57% in the uterus and increased to 141% in the spleen and 180% in the regional lymph nodes. When implantation was then initiated with the addition of oestradiol-17 beta to the progesterone treatment, amounts of TsF were increased to 206% in the uterus, 318% in the spleen, and remained unchanged at 180% in the regional lymph nodes. These experiments suggest that the amounts of TsF in the uterus and spleen are dependent upon the implantation process, whereas amounts of TsF in the regional lymph nodes are independent of this event.

Animals↗
PubMed1990

Investigations into the mechanism by which sodium fluoride stimulates prostaglandin production in guinea-pig uterus.

Sodium fluoride (10 mM) caused a slow increase in the outputs of PGF-2 alpha, 6-keto-PGF-1 alpha and, to a lesser extent, PGE-2 from the Day-7 and Day-15 guinea-pig uterus superfused in vitro. This stimulatory action of sodium fluoride was not prevented by using calcium-free Krebs' solution. There was also a faster stimulation of 6-keto-PGF-1 alpha output from the Day-7 guinea-pig uterus produced by sodium fluoride, and this quicker response was abolished by using calcium-free Krebs' solution. TMB-8 (an intracellular calcium antagonist) inhibited the stimulatory action of sodium fluoride on the outputs of PGF-2 alpha, PGE-2 and 6-keto-PGF-1 alpha from the Day-7 guinea-pig uterus. W-7 and trifluoperazine (calmodulin antagonists) and neomycin (an inhibitor of phospholipase C) had no inhibitory effect on the increases in outputs of PGF-2 alpha, PGE-2 and 6-keto-PGF-1 alpha from the Day-7 guinea-pig uterus produced by sodium fluoride. These results indicate that sodium fluoride slowly stimulates uterine PGF-2 alpha, PGE-2 and 6-keto-PGF-1 alpha synthesis in the guinea-pig uterus by mobilizing intracellular calcium by a mechanism which apparently does not involve the activation of phospholipase C or the participation of calmodulin (or a related compound). The initial, faster stimulation of 6-keto-PGF-1 alpha synthesis in the Day-7 guinea-pig uterus by sodium fluoride is dependent upon extracellular calcium.

6-Ketoprostaglandin F1 alpha↗
PubMed1993

Oxygen tension in the oviduct and uterus of rhesus monkeys, hamsters and rabbits.

Oxygen tension was measured using flexible polarographic microelectrodes within the oviductal and uterine lumen in rhesus monkeys (n = 9), golden hamsters (n = 21) and rabbits (n = 6), during the reproductive cycle (monkey), during oestrus and pseudopregnancy (hamsters, rabbits) and during pregnancy (hamsters). In general, oxygen tensions in each species were much less than half of atmospheric O2, ranging from high values of about 60 mm Hg (8.7% O2) in the rabbit oviduct, rabbit and hamster uterus, to as low as 11 mm Hg (1.5% O2) in the monkey uterus. Oxygen tensions did not vary significantly between left and right sides of the reproductive tracts (all species), nor between pregnant and pseudopregnant states nor between oviduct and uterus (hamsters). Differences owing to reproductive stage were found in the monkey oviduct, hamster oviduct and uterus, and rabbit uterus. Oxygen tensions were consistently very low (11-14 mm Hg) in the monkey uterus throughout the menstrual cycle. In hamsters and rabbits, intrauterine O2 decreased significantly at about the normal time of blastocyst formation and implantation, to 37 mm Hg (5.3% O2) and 24 mm Hg (3.5% O2), respectively. This study indicates that embryos develop in vivo under low oxygen concentrations, especially during the peri-implantation period. The data have implications for investigations of embryo metabolism and for improving embryo development in vitro.

Animals↗
PubMed2005

The IGF system in the neonatal ovine uterus.

Postnatal development of the ovine uterus primarily involves uterine gland morphogenesis or adenogenesis. Adenogenesis involves the budding differentiation of the glandular epithelium (GE) from the luminal epithelium (LE) and then GE proliferation and coiling/branching morphogenetic development within the stroma between birth (postnatal day or PND 0) and PND 56. Insulin-like growth factor (IGF)-I and IGF-II mRNAs were previously found to be expressed only in the endometrial stroma, whereas the IGF receptor (IGF-1R) mRNA was most abundant in epithelia and in stroma, suggesting that an intrinsic IGF system regulates postnatal development of the uterus. Given that the biological activities of IGFs are modulated by a family of six IGF binding proteins (IGFBPs) and specific proteases, the objective was to determine the effects of age and estrogen disruption on expression of IGFs, IGFBPs and pregnancy-associated plasma protein A (PAPP-A or IGFBP-4 protease) in the ovine uterus. In Study One, circulating levels of IGF-I and IGF-II in the serum of neonatal ewes did not change between PND 0 and PND 56. Levels of immunoreactive IGF-I, IGF-II and IGF-1R protein were most abundant on the apical surface of the endometrial LE and GE. RT-PCR analyses detected expression of IGFBPs (3, 4, 5 and 6) as well as PAPP-A mRNAs in the uterus, but not IGFBP-1 and IGFBP-2 mRNAs. IGFBP-3 and IGFBP-4 mRNAs were expressed specifically in the endometrial stroma and myometrium and increased after birth. PAPP-A mRNA was expressed specifically in the endometrial stroma and increased after birth. In Study Two, ewes were treated from birth with estradiol-17beta valerate (EV), which reduces uterine growth and inhibits endometrial adenogenesis. On PNDs 14 and 56, IGFBP-3 mRNA was decreased in the uterus of EV-treated ewes, but IGF-1R and IGFBP-4 mRNAs were not affected. PAPP-A mRNA was increased by EV treatment on PND 14, but decreased on PND 56. These results support the hypothesis that an intrinsic IGF system in the uterus regulates epithelial-stromal interactions important for postnatal uterine growth and endometrial gland morphogenesis in the sheep.

Animals↗
PubMed1981

Concentrations of oestradiol and oestrone in plasma, uterus and other tissues of fetal guinea-pigs: their relationship to uptake and specific binding of [3H]oestradiol.

The concentrations of unconjugated oestradiol-17 beta and oestrone have been measured by radioimmunoassay in the plasma of fetal, newborn and immature guinea-pigs. In fetal plasma, the values of oestradiol ranged from 15 to 50 pg/ml with no significant variations with gestational age except for an abrupt increase at the very end of gestation (148 pg/ml). Low concentrations of oestradiol were also found postnatally (from not detectable to 31 pg/ml) as well as in maternal plasma (22 pg/ml). The values of oestrone were consistently higher in all plasma regardless of age (43--164 pg/ml). Oestrogen concentrations were also determined in the fetal uterus, lung, kidney and brain and were found to be as much as 60 times higher (per g tissue) than in plasma, especially in the fetal uterus which contained four to five times more than the other tissues. These data correlated well with a 20--90 times greater uptake of [3H]oestradiol by the fetal uterus compared with the other tissues after in-vivo administration of [3H]oestradiol to the fetuses. The selective retention of oestradiol was probably due to the presence of specific oestradiol binding in these fetal tissues, particularly in the uterus whose binding was 60--120 times higher than in the other fetal tissues. Thus, the levels of oestrogen in the circulation of fetal guinea-pigs are low, but the fetal uterus is capable of maintaining a higher concentration which may be important physiologically since oestradiol has been shown to evoke a biological response in the fetal guinea-pig uterus.

Animals↗
PubMed2006

Steroid hormone regulation of Clca3 expression in the murine uterus.

Progesterone (P4) and its cognate receptor, the progesterone receptor (PGR), have important roles in the establishment and maintenance of pregnancy in the murine uterus. In previous studies, using high-density DNA microarray analysis, we identified a subset of genes whose expression is repressed by chronic P4-PGR activation in the uterus. The Clca3 gene is one of the genes whose expression is the most significantly downregulated by P4 and PGR. In the present study, we performed real-time RT-PCR and in situ hybridization to investigate the regulation of Clca3 by P4 and determine the pattern of expression of Clca3 in the uterus during early pregnancy. This analysis shows that Clca3 mRNA transcripts were detected in the luminal and glandular epithelium of the pseudopregnant uterus at day 0.5 and that the expression of Clca3 was not detected after day 3.5. P4 represses Clca3 mRNA synthesis in the luminal epithelial and glandular epithelial cells of the uterus in ovariectomized wild-type mice, but not in Pgr knockout (PRKO) mice. Conversely, estrogen (E2) induces Clca3 expression in the luminal epithelium and glandular epithelium, and this induction was repressed by P4 in the murine uterus. Analysis of the promoter region of Clca3 by in silico and transient transfection analysis in HEC-1A cells identified the regulation of Clca3 by estrogen receptor-alpha (ESR1) within the first 528 bp of 5'-flanking region of the Clca3 gene. Our studies identified Clca3 as a novel downregulated gene of PGR that is a direct target of E2 regulation.

Animals↗