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PubMed1991

Receptors for insulin-like growth factor II in the rat uterus: characterization and variation throughout the estrus cycle.

This study was undertaken to identify uterine insulin-like growth factor II receptors and examine the regulation of these receptor levels throughout the estrus cycle. We have demonstrated IGF-II receptors in crude uterine membranes by binding and cross-linking experiments. IGF-II binding to the rat uterine membranes displayed time and temperature dependence and maximum binding was achieved by 2 h at 22 degrees C. Uterine IGF-II binding sites were specific for binding IGF-II peptide and demonstrated negligible binding affinity for IGF-I and no affinity for insulin. The specific anti-IGF-II receptor antibody, R-II-PAB1, blocked the specific [125I]IGF-II binding to uterine membranes in a dose-dependent manner. The characteristics of uterine IGF-II receptor are similar to those reported for other tissues, with a single class of high-affinity binding sites with an apparent dissociation constant of 1.2 +/- 0.5 nmol/l and Beta max of 2.65 +/- 0.41 pmol/mg protein. Affinity cross-linking experiments indicated that the specific binding of [125I]IGF-II in the uterus is associated with a single band of protein with a mol wt of 250 kD. In mature cycling rats, the proestrus uterus had the lowest level of [125I]IGF-II binding per mg membrane protein, without changes in receptor affinity. However, because of greater yield of protein from proestrus uteri, the total [125I]IGF-II binding capacity of the uterus was similar to the other stages of the estrus cycle. These studies demonstrate the presence of authentic IGF-II receptors in the rat uterus and illustrate variations in the concentration of these receptors in the uterus throughout the estrus cycle.

Animals↗

PubMed1994

Functional relevance of luteinizing hormone receptor in mouse uterus.

The presence of high-affinity luteinizing hormone (LH)/human chorionic gonadotropin (hCG) receptors has been reported in porcine, rabbit, rat and human uteri. We have demonstrated binding of [125I]LH to mouse uterus, which was saturable. Scatchard plot analysis indicated Kd to be 1.37 x 10(-10) mol/l and the maximum binding capacity to be 5.24 nmol/kg protein. Attempts have been made to observe the functional relevance of gonadotropin receptor in the mouse uterus. The size and weight of the uterus remarkably decreased as a result of ovariectomy; administration of LH to ovariectomized (OVX) mice significantly increased the uterine weight in comparison to the OVX control (p < 0.01), indicating a direct effect of LH on the uterus. There was a two-fold decrease of uterine ascorbic acid content in LH-treated OVX mice as compared to the intact control. The gain in uterine weight of OVX mice by LH was due to the increase in uterine protein synthesis. The stimulatory effect of LH on OVX mice uterus appears to be mediated via steroid hormones because it significantly augmented uterine mitochondrial steroidogenesis. Since 17 beta-estradiol (E2) is known to stimulate uterine protein synthesis, the circulatory level of E2 was determined in intact, OVX and OVX + LH-treated mice. A fall in the circulatory level of E2 occurred in OVX mice as compared to the control, while treatment of LH for 7 days (three injections) significantly elevated E2 levels in OVX mice (p < 0.001). This higher level of E2 in OVX mice remains unaltered on adrenalectomy, indicating that adrenals are not the source for increased E2 levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗

PubMed1984

Effects of age and steroid treatment on prostaglandin production by the rat uterus in relation to implantation.

Prostaglandin (PG) production by the uterus of ovariectomized virgin rats, with and without replacement steroid therapy, was compared in animals aged 4-5 and 13-14 months. The synthesizing capacities of the uterus for PGE-2, PGF-2 alpha. 6-keto-PGF-1 alpha and thromboxane (TX) B-2 (expressed as the amounts synthesized per mg protein by the homogenized tissue during a 90-min incubation) were significantly lower in the ageing uteri than in young uteri. The PG and TX synthesizing capacities of the young uteri, but not of the ageing uteri, were stimulated by sequential treatment with oestradiol and progesterone implants. Tissue concentrations in and release from the uteri of PGE-2, but not of PGF-2 alpha, were significantly lower in ageing rats than in younger rats, and occurred irrespective of the hormonal status. Treatment with steroids did not stimulate the tissue concentrations in or release from the uterus of PGE-2 or PGF-2 alpha in young or ageing rats. Since PGs, particularly PGE-2, produced by the rat uterus have been implicated as mediators of the implantation process, reduced production of PGE-2 by the ageing uterus may explain the lower implantation rate and the consequent reduction in fertility of ageing rats.

6-Ketoprostaglandin F1 alpha↗

PubMed1999

Dominance of type 1 angiotensin II receptor in the nonpregnant and pregnant bovine uterus.

The present study was undertaken to characterize, determine and localize angiotensin II receptors in the nonpregnant and pregnant bovine uterus. In addition, the concentration of active renin, which is responsible for the generation of angiotensin, was determined. Autoradiography and angiotensin II receptor binding studies showed that all compartments of the bovine uterus contained high concentrations of angiotensin II receptors. In general, the type 1 angiotensin II receptor (AT1) predominated over the AT2 receptor. In the endometrium, the highest density was found in the caruncles and the AT1 receptor was always predominant. The density of angiotensin II receptors in the endometrium increased at the beginning of pregnancy, but decreased and reached values similar to those in nonpregnant animals near term. In the myometrium, the density of angiotensin II receptors was highest at or near the endometrial-myometrial junction. In this area, the predominant type of angiotensin II receptor in the uterus of cyclic cows varied, whereas the AT1 receptor always predominated during pregnancy. Non-AT1 and non-AT2 binding sites were found in the same locations as the angiotensin II receptors, but at lower densities. With the exception of the pregnant endometrium, all compartments contained higher active renin concentrations than found in plasma, indicating local synthesis of renin. This study demonstrates a difference in the expression of types of angiotensin II receptor in the bovine uterus compared with other species. The high densities of angiotensin II receptors localized in several important areas imply that the renin-angiotensin system participates in regulation of growth and tissue function in the bovine uterus.

Animals↗

PubMed2004

Real-time dynamics of prostaglandin F2alpha release from uterus and corpus luteum during spontaneous luteolysis in the cow.

Prostaglandin (PG) F2alpha released from the uterus in a pulsatile fashion is essential to induce regression of the corpus luteum (CL) in the cow. In addition to the uterus, the CL has also been recognized as a site of PGF(2alpha) production. Therefore, this study aimed to determine the detailed dynamics of the releasing profile of CL-derived PGF2alpha together with uterus-derived PGF2alpha during spontaneous luteolysis in the cow. Non-lactating Holstein cows (n = 6) were surgically implanted with a microdialysis system (MDS) on day 15 (oestrus = day 0) of the oestrous cycle. Simultaneously, catheters were implanted to collect ovarian venous plasma ipsilateral to the CL as well as jugular venous plasma. The concentrations of PGF2alpha, 13,14-dihydro-15-keto-PGF2alpha (PGFM) and progesterone in the MDS and plasma samples were determined by enzyme immunoassays. The intra-luteal PGF2alpha secretion slightly increased after the onset of luteolysis (0 h) and drastically increased from 24 h, and was maintained at high levels towards the following oestrus. Furthermore, PGF2alpha was released from the CL into the ovarian vein in a pulsatile manner during spontaneous luteolysis. Also, the fact that intra-luteal secretion of PGF2alpha and PGFM showed a positive correlation indicates the existence of a local metabolic pathway for PGF2alpha in the CL. In conclusion, the present study clarified the real-time dynamics of uterus-derived PGF2alpha and CL-derived PGF2alpha during spontaneous luteolysis in the cow, and gives the first in vivo evidence that the CL releases PGF2alpha during spontaneous luteolysis in the cow. Although the physiological relevance of CL-derived PGF2alpha appears to be restricted to a local role as an autocrine/paracrine factor in the CL, overall results support the concept that the local release of PGF2alpha within the regressing CL amplifies the luteolytic action of PGF2alpha from the uterus.

Animals↗

PubMed2005

Differential expression of mesotocin receptors in the uterus and ovary of the pregnant tammar wallaby.

Mesotocin, an oxytocin-like peptide, is released in highest concentrations during parturition in macropodid marsupials. In late pregnant wallabies, uterine sensitivity to mesotocin increases markedly in the myometrium of the gravid uterus. This coincides with a significant increase in myometrial mesotocin receptor concentrations 3-4 days before term. To date, there is no information on mesotocin receptor gene expression in female wallaby reproductive tissues. This study aimed to examine mesotocin receptor gene expression in the uterus and ovaries of pregnant tammar wallabies, and to localise mesotocin receptors within the uterus. An RT-PCR strategy produced a consensus nucleotide sequence of 834 bp, which encoded 278 amino acids of transmembrane domains I to VI. This protein sequence has approximately 80% homology with the bovine and rat oxytocin receptor exon 2 region. Only one mesotocin receptor was detected in the tammar genome. The myometrium and mammary gland both expressed a 4.1 kb mesotocin receptor gene transcript. Myometrial mesotocin receptor gene expression increased on day 22 of the 26-day gestation and was significantly higher in the gravid than the non-gravid uterus in late pregnancy. This pattern of mesotocin receptor gene expression paralleled mesotocin receptor concentrations. Mesotocin binding sites were localised only to the myometrium, the highest densities being observed in the gravid uterus. Finally, this study showed high expression of mesotocin receptors in the corpus luteum. The pattern of luteal mesotocin receptor expression differed from the myometrium, with a decrease in mesotocin receptors occurring on the day of expected births.

Amino Acid Sequence↗

PubMed2006

Magnetic resonance imaging of morphological and functional changes of the uterus induced by sacral surface electrical stimulation.

The purpose of this study is to examine the morphological and kinematical changes of the uterus induced by electrical stimulation applied to the skin just above the second and fourth posterior sacral foramens (sacral surface electrical stimulation [ssES]) in 26 healthy subjects. Out of them, eight subjects who had severe pain subjectively during every menstruation received ssES just in menstruation. Morphological and functional changes of the uterus were examined by using T2-weighted magnetic resonance (MR) imaging and T1-weighted MR cinematography, respectively. Cyclic electrical stimulation for 15 min with 5 sec ON and 5 sec OFF was applied just before MR scanning. A decrease in thickness of the muscular layer of the uterus was observed in every subject after ssES for 15 min and was significant as compared with the thickness before ssES. Periodic uterine movement during menstruation was observed in the subjects with severe menstrual pain in MR cine and the power spectrum analysis of the movement showed a marked decrease in peak power and frequency after ssES treatment. We conclude that ssES causes a reduction of static muscle tension of the uterus in all menstrual cycle periods and suppression of uterine peristalsis during menstruation in the subjects with severe menstrual pain. Possible neural mechanisms for these static and dynamic effects of ssES on the uterus at spinal level are discussed.

Adult↗

PubMed2001

Endothelin-1 in smooth muscle cells and mast cells of mouse uterus after parturition.

To elucidate the physiological importance of endothelin-1 (ET-1) in mouse uterus, we investigated quantitative changes in ET-1 mRNA levels in the uterus during the estrous cycle, pregnancy and post-parturient period by use of the real-time PCR technique and we examined the cellular distribution of the ET-1 peptide by use of immunohistochemical techniques. Low and constant mRNA levels were observed in the uterus from cyclic or pregnant mice. However, a significant increase in mRNA levels was found immediately after parturition (day 0 postpartum) which then decreased gradually to a basal level at day 14 postpartum. Discernible immunopositivity was found in myometrial cells as well as in endometrial epithelial cells in the post-parturient uterus. Myometrial cells showed the strongest staining at day 0 postpartum, and some large cells in the myometrial layers, intensely positive for ET-1, were characterized as mast cells. These findings suggest the possibility that in mouse uterus ET-1 may play a role in recovery from the uterine changes caused by pregnancy and parturition.

Animals↗

PubMed1984

Induction of cytosolic receptors for 1 alpha, 25-dihydroxyvitamin D3 in the immature rat uterus by oestradiol.

The role of oestradiol-17 beta in the induction of specific cytosolic receptors for 1 alpha,25-dihydroxyvitamin D3 (1,25(OH)2D3) was examined in the immature rat uterus. An acrylamide gel electrophoretic analysis was developed to separate the specific receptor for 1,25(OH)2D3 from the plasma binding protein for vitamin D3 metabolites. Employing this sensitive method the presence of receptors for 1,25(OH)2D3 in the mature rat uterus was evident. Such receptors were not found in the uterus of saline-treated immature rats. However, oestradiol administration caused an induction of these receptors in the immature rat uterus, together with a significant increase in the uterine weight, progesterone receptor level and peroxidase activity. These results suggest a mechanism for oestradiol regulation of calcium metabolism in the uterus at times of high demand for this cation during the gestation period.

Animals↗

PubMed1987

Effects of the uterus and the ovaries on growth, somatotropin and somatomedin A in developing rats.

The effects of hysterectomy and ovariectomy on plasma concentrations of GH, somatomedin A, TSH and thyroxine (T4) were studied in developing rats. Four groups of 24-day-old rats were ovariectomized, ovohysterectomized, hysterectomized or sham-operated. Their weights, lengths and plasma hormone concentrations were measured at 26, 43, 64, 78 and 92 days of age to investigate pre- and postpubertal differences caused by the uterus or ovaries. Plasma concentrations of the hormones examined showed a successive rise with time, but GH and somatomedin A concentrations rose mainly after the opening of the vagina (days 50-55). Higher GH and somatomedin A concentrations were found in the plasma of ovariectomized animals than in ovohysterectomized controls before puberty (GH: 260-300%, P less than 0.01; somatomedin A: 25-30%, P less than 0.05). Ovariectomized animals weighed more than ovohysterectomized females after puberty (4.5-6%, P less than 0.01). This indicated that the uterus exerted a stimulatory effect on GH-somatomedin A regulation and body weight gain in the absence of the ovaries. Significantly lower plasma somatomedin A (but not GH) concentrations were found in hysterectomized and sham-operated animals than in their respective controls after puberty (30-39%, P less than 0.01) and their final body weight was lower (22-26%, P less than 0.001). There were no consecutive uterus- or ovary-related changes in plasma TSH and T4 levels. It was concluded that both the uterus and ovaries had significant as well as opposite effects on somatomedin A and body weight with the effects of the ovaries being greater than those of the uterus.

Animals↗

PubMed1998

Expression of macrophage colony-stimulating factor, scavenger receptors, and macrophage proliferation in the pregnant mouse uterus.

During pregnancy, mouse uterine epithelial cells produce and secrete a large amount of macrophage colony-stimulating factor (M-CSF/CSF-1). Macrophages accumulate and proliferate in the undecidualized endometrium of the pregnant uterus. Observations showed that macrophages expressed scavenger receptor class A (type I and type II) and class C (macrosialin). Scavenger receptors appeared to be involved in the removal of apoptotic cells in the degenerated decidual tissue. The expression of class A and class C scavenger receptor mRNAs in the uterus of pregnant mice was elevated but the expression of class B scavenger receptor (CD36) mRNA was similar to that of non-pregnant mice. The expression of various cytokines and chemokines, including M-CSF, monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein 1-alpha (MIP1-alpha), was enhanced in the uterus of pregnant mice, suggesting that these molecules regulate macrophage chemotaxis and immunological function in the uterus. These findings imply that the pregnant uterus provides a microenvironment for the recruitment, differentiation, and proliferation of macrophages and the regulation of scavenger receptor and cytokine expression for a successful pregnancy.

Animals↗

PubMed1997

Changes in myosin heavy chain (MHC) expression during pregnancy in rat uterus.

Expression of myosin heavy chain (MHC) was investigated in rat uterus during pregnancy. Two MHC isoforms, SM MHCI (204 kDa) and SM MHCII (200 kDa), were resolved following the analysis of Guba Straub extract of non-pregnant and pregnant uterus using sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). Whereas SM MHCI showed an increase from 69.26 +/- 3.26% in nonpregnant uterus to 81.40 +/- 5.36% in pregnant uterus, the SM MHCII exhibited a corresponding decline from 30.73 +/- 3.29 to 18.59 +/- 5.36%. The native myosin separated under non-dissociating conditions and subsequently analyzed in denaturing SDS-PAGE also demonstrated two MHC isoforms with identical electrophoretic mobilities. A SDS-PAGE analysis of native myosin from pregnant rats extracted at room temperature and in the absence of proteolytic inhibitors revealed a characteristically increased proteolysis of MHC into two peptide products of 153 and 140 kDa during pregnancy. Such a proteolysis of MHC, but in very low proportions, was noticed in nonpregnant uterus too.

Animals↗

PubMed1991

Biochemical analysis of glycosphingolipids in murine uterus and human uterine endometrium with special reference to the sexual cycle.

Uterus is an organ in which cellular proliferation and differentiation are strictly controlled by sex steroid hormones. Since we found a characteristic expression of sulfatide (I 3SO3-GalCer) in the human endometrium during its secretory phase, we decided to analyze developmental changes of glycolipids in murine uteri with special reference to the estrous cycle. Moreover, we analyzed sulfotransferase activity for the synthesis of sulfatide in the endometria in the proliferative and secretory phases and that in the epithelial and stromal cells derived from the human uterine endometrium. In the murine uterus, contents of GlcCer, LacCer, and Gb4Cer were relatively constant both during estrus and diestrus, but those of Gb3Cer and Gg4Cer during estrus were significantly greater than those during diestrus. In contrast, GM3 and sulfatide contents during diestrus were higher than those during estrus. This increase in GM3 and sulfatide during diestrus was characteristically observed in the uterus after sexual maturity. In human uterine endometrium, sulfotransferase activity for the synthesis of sulfatide was found only in the epithelial cells, but not in the stromal cells. Furthermore, the synthetic potential of sulfatide in the human endometrium was higher in the secretory phase than in the proliferative phase. Thus, sulfatide metabolism in human endometrial epithelial cells as well as in the murine uterus is supposed to be well controlled under hormonal regulation, and sulfatide may participate in several reproductive functions of the uterus.

Animals↗

PubMed1994

The effect of platelet activating factor antagonist (BN 52021) on pregnancy duration and collagen content in the pregnant rat uterus and cervix.

In order to study the role of Platelet Activating Factor (PAF) in the mechanism of parturition and connective tissue metabolism in the pregnant rat uterus, we investigated the influence of the Platelet Activating Factor Receptor Antagonist (BN 52021) on gestation duration and collagen concentration in pregnant rat uterus and cervix at term. Total and soluble collagen as well as dry tissue/wet tissue ratio were measured in the BN 52021 treated group (n = 9) and in the control group (n = 13). Gestation duration was evaluated in a group receiving BN 52021 (n = 10) and in a control group (n = 19) receiving pure solvent. There were no significant differences in water content. The total and soluble collagen concentration was also similar to the control in both the uterus and the cervix. The only significant difference was observed in the soluble collagen/total collagen ratio in the uterus. BN 52021 administration did not alter the gestational period. Basing on this experiment we suggest that not all the phospholipid metabolites activated by phospholipase A2 significantly influence the duration of pregnancy and connective tissue metabolism in the pregnant rat uterus.

Animals↗

PubMed1994

Differential reduction in the volume of leiomyoma and uterus during buserelin treatment.

Twenty-four women (mean age 42.0 +/- 2.4 years) with leiomyoma underwent treatment with a gonadotropin releasing hormone (GnRH) agonist (buserelin) for 6 months at a dose of 1200 micrograms daily intranasally for the first 2 months, followed by 900 micrograms daily for 4 months. The volume of the uterus and of individual leiomyomas were measured by echosonography before treatment, every 2 months during treatment, and every 2 months for 6 months after cessation of therapy (a total of 7 evaluations). A control group, comprising 14 women with untreated leiomyoma, underwent ultrasound scanning every 2 months for 6 months. A significant reduction in the volume of the uterus and leiomyomas was observed after the first 2 months of treatment in all but one patient. Leiomyomas showed a greater reduction in volume (54.6 +/- 2.2%) than did the uterus (41.8 +/- 2.3%; p = 0.0003). They also showed a more rapid increase in volume after cessation of therapy (p = 0.03). The control group showed an insignificant increase in the size of the uterus and individual leiomyomas over the 6 months' monitoring. The differences observed in reduction of the volumes of the leiomyomas and the uterus during the state of hypoestrogenism induced by buserelin, as well as in their regrowth after cessation of treatment, can be explained by the greater number of estrogen receptors in leiomyoma tissue and a possible lower rate of conversion of estradiol into estrone.

Adult↗

PubMed2000

Genistein regulation of transforming growth factor-alpha, epidermal growth factor (EGF), and EGF receptor expression in the rat uterus and vagina.

Epidemiological reports and laboratory data have associated soy and genistein with reduced incidence of uterine, breast, and prostate cancers, cardiovascular disease and osteoporosis, and lower total blood cholesterol. The aim of this study was to investigate the effect of genistein in the uterus and vagina of rats, focusing our attention on the distribution of transforming growth factor (TGF) alpha, epidermal growth factor (EGF), and EGF receptor. A pharmacological dose of genistein (500 microg/g body weight) injected in rats on days 16,18, and 20 postpartum resulted in significant uterine wet weight gain, with hypertrophy of the luminal and glandular epithelium of the uteri, and squamous epithelium of the vagina in 21-day-old animals. At 50 days of age, hypertrophy was no longer evident in the uterus and vagina. Prepubertal genistein treatment resulted in significantly increased EGF immunostaining in individual stromal cells and reduced EGF receptor immunostaining in blood vessels of the uterus. Genistein-treated rats had decreased TGF-alpha immunostaining in glandular and luminal epithelium and a slight increase in EGF receptor immunostaining in stromal cells of the uterus. This suggests paracrine interaction between cells elevating the level of EGF ligand in the stroma and the EGF receptor in the luminal and glandular epithelium, resulting in uterine hypertrophy. In the vagina, genistein did not cause significant alterations to the EGF-signaling pathway in 21- and 50-day-old rats. We conclude that pharmacological doses of genistein during the prepubertal period can modulate the EGF-signaling pathway in the uterus and exert a uterotrophic response in a short-term manner.

Animals↗

PubMed2000

Defective macrophage recruitment and clearance of apoptotic cells in the uterus of osteopetrotic mutant mice lacking macrophage colony-stimulating factor (M-CSF).

There are large numbers of macrophages in the uterus of normal mice. During estrus and metestrus endometrial epithelial cells express macrophage colony-stimulating factor (M-CSF). Numbers of uterine macrophages showed cyclic changes and accumulated beneath the endometrial epithelial cells at estrus and metestrus. However, numbers of uterine macrophages in osteopetrotic (op/op) mice were reduced tenfold compared with normal littermate mice and op/op mouse macrophages were ultrastructurally immature throughout the estrous cycle. Several macrophage chemokines were produced in the uterus. However, administration of antibody against the macrophage colony stimulating factor receptor (c-fms) severely diminished the number of uterine macrophages in normal littermate mice, implying that M-CSF plays a major role in macrophage recruitment in the uterus. Endometrial epithelial cells underwent apoptosis at estrus and metestrus and were disposed into the uterine lumen in op/op mice and littermate mice. In littermate mice a large number of macrophages accumulated beneath the endometrial epithelial cells and actively removed apoptotic cells. In contrast, there were few macrophages in op/op mice and clearance of apoptotic cells by macrophages was defective in the uterus of these mice. Thus M-CSF plays important roles in the recruitment and differentiation of macrophages and in scavenging effete epithelial cells in the uterus.

Animals↗

PubMed2001

The blood vasculature as the forming element of the uterus of the estrous donkey (Equus asinus).

Light, scanning electron microscopy of endometrial surface and vascular casts were used to study the vascular architecture of the donkey uterus during estrous. The arterial blood supply of the uterus comes from three arteries: the uterine branch of the ovarian artery, the uterine artery of the external iliac artery, and the uterine branch of the urogenital artery. All arteries enter the uterus at its mesometrial border and divide into smaller ones. Segmentally constricted arteries are seen to circumscribe large veins at the perimetrium which become highly convoluted in the intermuscular vascular layer of the myometrium. Small arteries and arterioles originate at the borderline between the myometrium and the endometrium and radiate to the surface of the endometrium to constitute a system of numerous ridges and grooves by a widely meshed plexus of subepithelial capillary network. The post-capillary venules of the endometrium arise from the subepithelial capillary plexus to form slightly larger veins than the concurrent arteries which join up to the large tortuous veins in the intermuscular vascular layer of the uterus. This arrangement of blood vessels in the donkey uterus and particularly in the endometrium provides the requirement for instant blood flow on the arterial side and for the slow flow rate on the venous side to ameliorate the process of substances exchange.

Animals↗