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PubMed2001

William Hunter's casts of the gravid uterus at the University of Glasgow.

The Hunterian Collection at the University of Glasgow possesses 11 plaster casts showing the pregnant uterus. Three correspond to Plates I, IV, and VI of Hunter's The Anatomy of the Gravid Uterus Exhibited in Figures (1774), progressive stages of dissection of the same specimen. A further three casts show consecutive stages of dissection of a uterus containing a fetus presenting by the breech. The other specimens show a normal pregnancy at about 6 months, a normal full-term uterus with the fetal head becoming engaged, a breech presentation with placenta previa and the umbilical cord around the fetal neck, and an obstructed labor with distended bladder and colon. The 10 on display show realistic coloring and are mounted on black wooden stands. An 11th specimen, amateurishly painted, is not on display. The casts differ in their style; some show only the abdomen, pelvis, perineum, and thighs, others show the full torso. They also differ in the amount of detail shown. The first three casts show the cut femur and muscles at the transected ends of the thighs, also shown in some of the plates in the Gravid Uterus. Although these features enhance the artistic impact of both the engravings and the casts, the authors are unconvinced that Hunter deliberately used them to achieve this, as has been claimed.

Adult↗
PubMed1993

Expression of four myosin heavy chain isoforms with development in mouse uterus.

In smooth muscle tissue, two or three isoforms of myosin heavy chain (MHC) have been reported (SM1, SM2, and/or NM). In mouse uterus tissue, four bands in the region of the MHC's can be resolved on high resolution SDS polyacrylamide gels. Western blots using smooth muscle (SM) MHC-specific and nonmuscle (NM) MHC-specific polyclonal antibodies show the upper two bands in the MHC region are SM isoforms, whereas the lower two bands are NM isoforms. One-dimensional peptide maps of these four bands show each to have a unique pattern of polypeptide fragments following alpha-chymotrypsin digestion. Developmental expression of myosin heavy chains (MHC) in mouse uterus, aorta, bladder, and stomach (6 ages, 10-150 days) was determined using tissue homogenates. In the uterus, both SM MHC's show an increase in relative content with increasing age, whereas the NM MHC's show a decrease. The mouse aorta shows a significant increase in the SM MHC's and a significant decrease in the NM MHC from day 10 to day 30, which is similar to data reported for the rat aorta. Whereas both the bladder and stomach contain relatively small amounts of NM MHC's (approximately 10% or less), these quantities do show decreases with development. The SM1:SM2 ratio for the uterus remains high (3.4 at 150 days) through development; the aorta, bladder, and stomach also start out high, but tend toward 1.0 in the 150-day animals. The presence of four MHC isoforms in the uterus with unique developmental regulation of expression is consistent with hypotheses of unique functional roles for these isoforms.

Analysis of Variance↗
PubMed1986

Estradiol receptor: phosphorylation on tyrosine in uterus and interaction with anti-phosphotyrosine antibody.

Estradiol receptor from rat uteri incubated with [32P] orthophosphate has been purified by diethylstilbestrol--Sepharose followed by heparin--Sepharose chromatography. The purified receptor, analyzed by centrifugation through sucrose gradients after incubation with monoclonal antibodies against purified estradiol receptor, appears to be labeled with 32P. The receptor preparation has been further purified by immunoaffinity chromatography and submitted to SDS--poly-acrylamide gel electrophoresis. A heavily 32P-labeled 68 kd protein and a very lightly 32P-labeled 48 kd protein, probably a proteolytic product of the 68 kd protein, were detected. Phosphoamino acid analysis of the receptor eluted from the immunoaffinity column shows that its 32P-labeling occurs exclusively on tyrosine. This is the first report on phosphorylation on tyrosine of a steroid receptor in tissue. It is consistent with our previous finding that a uterus estradiol receptor-kinase, which confers hormone binding ability to the estradiol receptor, in vitro phosphorylates this receptor exclusively on tyrosine. Calf uterus receptor binds with high specificity and affinity to monoclonal anti-phosphotyrosine antibodies covalently bound to Sepharose (Kd = 0.28 nM). Dephosphorylation of the receptor by nuclei containing the calf uterus nuclear phosphatase abolishes the interaction with antibodies. These results suggest that also in calf uterus, estradiol receptor is phosphorylated on tyrosine. Anti-phosphotyrosine antibodies bound to Sepharose have been used to partially purify the estradiol receptor from calf uterus.

Animals↗
PubMed2005

Contribution of three-dimensional volume contrast imaging to the sonographic assessment of the fetal uterus.

OBJECTIVE: To investigate the contribution of volume contrast imaging (VCI) in assessing the fetal uterus in normally developed female fetuses. METHODS: The pelvis of 38 normal female fetuses was examined at 20-22 and 32-34 weeks' gestation using both conventional two-dimensional (2D) ultrasound and VCI on the same transverse or oblique longitudinal view of the fetal pelvis. Two experienced sonographers evaluated the ability of both techniques to image the fetal uterus. Results were compared by kappa index to evaluate the interobserver variability. RESULTS: A clear picture of the fetal uterus was obtained in 50% and 82-87% of the cases at 20-22 weeks' gestation and in 80-85% and 95-100% of the cases at 32-34 weeks' gestation using conventional 2D ultrasound and VCI, respectively. There was moderate to good agreement of uterus visualization between the two observers, with kappa values ranging from 0.43 to 0.65. The lower level of agreement was obtained for conventional 2D ultrasound during the second trimester. CONCLUSIONS: Our results suggest that VCI may be successfully applied to prenatal ultrasonography of the fetal pelvis anatomy. By enhancing the contrast between the intrapelvic organs, VCI provides a clearer picture of the fetal uterus.

Chi-Square Distribution↗
PubMed1993

Nitric oxide synthase activity in the pregnant uterus decreases at parturition.

The mechanisms that mediate changes in uterine activity from a quiescent state during pregnancy to active labor at parturition are unknown. Nitric oxide (NO), a potent mediator of smooth muscle relaxation, and its presence in the uterus is the subject of this report. Nitric oxide synthase (NOS) activity was demonstrated in nerves, blood vessels and decidua of gravid rat uterus by the NADPH-diaphorase staining method. Uterine tissue fixed during labor demonstrated markedly less NOS. Quantitation of NOS activity in subcellular fractions of pregnant and laboring uterus revealed its presence in both the cytosolic and the membranous compartments of uterine homogenates. In both cellular subfractions the enzyme activity decreased significantly from pregnancy to term. We conclude NOS is present in multiple structures within the uterus. Its presence in two cellular compartments suggests more than one form of NOS may be present in the uterus. Reduction in NOS activity at parturition suggests NO may contribute to the maintenance of uterine contractile quiescence during gestation.

Amino Acid Oxidoreductases↗
PubMed2002

Influence of estradiol and gestagens on oxidative stress in the rat uterus.

OBJECTIVE: We studied the effect of ovariectomy, estradiol (E2), and E2 + medroxyprogesterone (MPA) on the Wistar rat uterus. METHODS: We used 15 adult female rats. The study was divided into the following four stages: (a) extirpation of the upper half of the left hemi-uterus (basal state) and ovariectomy; (b) animals were maintained for 15 days without treatment, performance of a new laparotomy, and extirpation of the remaining left hemi-uterus (OVX state); (c) beginning of E2 replacement therapy (ERT) (8 microg/day) for 15 days, followed by extirpation of the upper half of the right hemi-uterus (ERT state); and (d) the administration of E2 was continued, and oral treatment with MPA was begun (20 microg/day) to last for a further 15 days. At the end of the combined hormone replacement therapy (HRT) the remaining right hemi-uterus was extirpated (HRT state). At the end of each intervention, the plasma concentrations of E2 and PRG were measured. RESULTS AND DISCUSSION: The ovariectomy significantly reduced the malonaldehyde (MDA) levels (P < 0.0008) and catalase activity (P < 0.0006). The ERT very significantly (P < 0.0033) raised the catalase and MDA levels; these significance levels were maintained after the Bonferroni method was applied (overall error 5%). The HRT reduced the levels of MDA and catalase, but not significantly after the Bonferroni test was applied.Conclusions. Uterine oxidative stress is increased by E2, resulting in a significant increase in MDA. This may be modulated in part by the catalase activity. Although it cannot be confirmed categorically, MPA seems to intervene by decreasing the said oxidative stress.

Animals↗
PubMed1995

Muscarinic receptor subtypes in normal, fetal, and gravid rabbit bladder, heart and uterus.

In the rabbit bladder, pregnancy has been shown to induce a significant decrease in both muscarinic receptor density and response to muscarinic stimulation. Neonatal rabbit bladders have a high muscarinic receptor density and contractile response to bethanechol stimulation. The bladders from 7 gravid rabbits, 7 age-matched virgin controls, and 32 fetal rabbits of 3 week gestation were studied. Compared to control tissue, filtration binding demonstrated receptor density to be 24.3% lower in gravid bladder dome, 41.2% lower in gravid bladder base, and 114.8% higher in fetal bladders. While total receptor density was not different from control in gravid heart, fetal hearts showed a 2.5 fold increased receptor density. There was also a 61% reduction in muscarinic receptor density in the gravid uterus. Immunoprecipitation assays using muscarinic receptor subtype specific antisera were used to measure the relative levels of m1, m2, m3 and m4 receptors. The m2 receptor was the predominant subtype in the bladder and uterus, and the only subtype detected in rabbit heart. The m3 receptor protein was also present, but in lower levels in the bladder and uterus. The m1 and m4 receptors were not detected in any of the tissues studied. Furthermore, the relative percent of each receptor did not statistically change for the gravid or fetal rabbit bladder, uterus, or heart, when compared to its control. Differences in the contractile response to cholinergic stimulation of the gravid bladder and uterus, and of the fetal bladder then, can be attributed to changes in muscarinic receptor density and not to changes in receptor subtype.

Animals↗
PubMed1988

Relaxant effect of dopamine on the isolated rat uterus.

The effect of dopamine was studied on the isolated uterus of diethylstilboestrol-treated rats. Dopamine, at concentrations (10(7)-10(-4) M) produced a concentration-dependent relaxation in the K+-depolarized rat uterus. On a molar basis, dopamine was about 500 times less potent than adrenaline in relaxing the uterus, the maximum degree of relaxation obtained with both drugs was the same. Pretreatment of the rats with reserpine (5 mg/kg) did not produce any modification of the dose-response curve to dopamine. Similarly, cocaine (3 x 10(-6) M) failed to modify the relaxant effect of dopamine. The dopamine induced relaxation was inhibited by propranolol (10(-9)-10(-7) M) in a dose-dependent manner. Prazosin (10(-7) M), SCH 23390 (10(-7) M) and sulpiride (10(-7) M) did not affect the dopamine dose-response curve. In the isolated rat uterus which was not preconstricted by KCl neither dopamine nor adrenaline produced any effect when added to the organ bath. This lack of response to both catecholamines was present even in tissues pretreated with propranolol or sulpiride. It is concluded that dopamine produced a concentration-dependent relaxation of the uterus from diethylstilboestrol-treated rats by direct activation of beta-adrenoceptors. There was no evidence for indirect action (catecholamine release and neuronal uptake mechanisms) and specific dopamine receptor mediated relaxation and alpha-adrenoceptor mediated contractions have not been found in this preparation.

Animals↗
PubMed1995

Nitric oxide nerves in the uterus are parasympathetic, sensory, and contain neuropeptides.

Nitric oxide (NO) is synthesized in neurons and is a potent relaxor of vascular and nonvascular smooth muscle. The uterus contains abundant NO-synthesizing nerves which could be autonomic and/or sensory. This study was undertaken to determine: 1) the source(s) of NO-synthesizing nerves in the rat uterus and 2) what other neuropeptides or transmitter markers might coexist with NO in these nerves. Retrograde axonal tracing, utilizing Fluorogold injected into the uterine cervix, was employed for identifying sources of uterine-projecting neurons. NO-synthesizing nerves were visualized by staining for nicotinamide adenine dinucleotide phosphate (reduced)-diaphorase (NADPH-d) and immunostaining with an antibody against neuronal/type I NO synthase (NOS). NADPH-d-positive perikarya and terminal fibers were NOS-immunoreactive (-I). Some NOS-I/NADPH-d-positive nerves in the uterus are parasympathetic and originate from neurons in the pelvic paracervical ganglia (PG) and some are sensory and originate from neurons in thoracic, lumbar, and sacral dorsal root ganglia. No evidence for NOS-I/NADPH-d-positive sympathetic nerves in the uterus was obtained. Furthermore, double immunostaining revealed that in parasympathetic neurons, NOS-I/NADPH-d-reactivity coexists with vasoactive intestinal polypeptide, neuropeptide Y, and acetylcholinesterase and in sensory nerves, NOS-I/NADPH-d-reactivity coexists with calcitonin gene-related peptide and substance P. In addition, tyrosine hydroxylase(TH)-I neurons of the PG do not contain NOS-I/NADPH-d-reactivity, but some TH-I neurons are apposed by NOS-I varicosities. These results suggest NO-synthesizing nerves in the uterus are autonomic and sensory, and could play significant roles, possibly in conjunction with other putative transmitter agents, in the control of uterine myometrium and vasculature.

Amino Acid Oxidoreductases↗
PubMed1992

Immunohistochemical localization of the eosinophil major basic protein in the uterus horn and cervix of the rat at term and after parturition.

Distribution of the eosinophil major basic protein (MBP) was studied in the rat uterus horn and cervix by means of immunohistochemistry using an antiserum raised against rat MBP. Various hormonal contexts were investigated: pre- and post-parturition, the estrous cycle, and ovariectomy followed by hormonal treatment or without treatment. MBP was detectable in the cervix as early as 12 h post-partum, appearing in the stroma close to the myometrium. The MBP had spread throughout the stroma toward the luminal epithelium after a few days. In contrast, no MBP was seen in sections of the corresponding pre- and post-partum uteri and in the pre-partum cervix. In cycling rats, MBP was distributed equally in the cervix and uterus and was more abundant during proestrus and estrus. In ovariectomized rats subsequently treated with progesterone, no MBP was detected in the cervix or uterus. In the cervix of ovariectomized rats treated with estradiol, MBP first appeared in the muscle layer situated between the two cervical lumina and then reached the stroma; within a few days only the stroma was stained. Inversely, in the uterus MBP-staining first appeared in the stroma. In conclusion, analysis of the distribution of MBP in rat uterus revealed a marked difference in the response of the cervix and horn to a hormonal environment.

Animals↗
PubMed1978

[Metric growth of the uterus in digenetic trematodes (author's transl)].

1. The length of the uterus of Dicrocoelium dendriticum, Pleurogenoides medians and Fasciola hepatica at different stages of development is correlated with the corrected size of the body (parallel length x breadth). 2. The data plotted in a log-scale show for all three species a sigmoid curve with linear middle section. 3. The function y = ax + ac(xw - x)3 + b(y = log length of the uterus, x = log length of the body, xw = log length of the body at the turning point) fits very well to the data obtained from Dicrocoelium dendriticum. The constants a, ac and b were determined numerically. The function is valid also for Pleurogenoides medians and Fasciola hepatica but with other constants. 4. The linear middle section of the sigmoid curve may be interpreted by allometric growth. During this phase of development the uterus is tubelike. 5. During the earliest stages of development the uterus forms a solid cord of cells (three-dimensional growth) and grows slower than in a later stage after formation of a cell-free interior (two-dimensional growth). 6. The latest phases of development are characterized by a small increase in length of the uterus due to the three-dimensional dilatation by the produced eggs. 7. The computed function is considered as a modification of the law of allometric growth Y = B . Xa, respectively y = ax + b (log Y = y, log X = x).

Animals↗
PubMed1985

Neuropeptide Y (NPY)-like immunoreactivity in guinea pig uterus is reduced during pregnancy in parallel with noradrenergic nerves.

Neuropeptide Y (NPY) is a recently discovered neuropeptide with vasoconstrictor effects when given in vivo. It occurs in many sympathetic neurons, where it appears to coexist with noradrenaline (NA). It is wellknown that profound changes in the levels of uterine NA occur in many species during pregnancy. Therefore we have investigated the distribution of catecholamine neurons and NPY by immunohistochemistry in the pregnant and nonpregnant guinea pig uterus. In the virgin uterus NPY-like immunoreactivity was present in nerve fibres and terminals in the smooth muscle layers of the uterine horns and around blood vessels. The distribution of NPY fibres was very similar to that of noradrenergic nerves visualized with antibodies against the catecholamine synthesizing enzyme tyrosine hydroxylase (TH). In the pregnant uterus, NPY- and TH-like immunoreactivity disappeared almost completely. In the cervix, a slight decrease of immunoreactivity was observed, whereas in the ovaries no changes were noted between the pregnant and nonpregnant condition. The results indicate that NPY and catecholamines coexists in the adrenergic neurons of the guinea pig uterus, cervix and ovary and that they vary together in the myometrium during pregnancy. We suggest that NPY may be of functional importance for the pregnant uterus.

Adrenergic Fibers↗
PubMedDate not supplied

Expression of steroid receptors in intact rat uterus, mammary gland, and liver treated with selective estrogen receptor modulators and conjugated equine estrogens.

The aim of the present study was to determine the effects of conjugated equine estrogens (CEE) and selective estrogen receptor modulators (SERM) (tamoxifen [TAM] and raloxifene [RAL]) on the expression of steroid receptors-estrogen receptor (ER) and progesterone receptor (PR)-in intact rat uterus, mammary gland, and liver. A total of 24 female rats weighing 250 to 300 g were randomized into 4 groups. Groups 1, 2, 3, and 4 were respectively given conjugated equine estrogen, tamoxifen, raloxifene, and vehicle for a 28-day period. ER and PR expression was detected in tissues of the uterus, mammary gland, and liver. Uterine wet weight and serum estradiol levels were established for all groups. No statistical difference was observed between groups in the ER expression of mammary gland and liver and in the PR expression of uterus, mammary gland, and liver, but differences were noted in serum estradiol levels and uterine ER expression. Serum estradiol levels were lower in the TAM-treated group; differences between the TAM-treated group and the other groups were statistically important (P<.05). Uterine ER expression was greater in the CEE-treated group; differences between the CEE-treated group and the TAM- and RAL-treated groups were statistically important (P<.05). CEE or SERM versus vehicle treatment in controls did not seem to result in statistically important differences in ER and PR expression in intact rat uterus, mammary gland, and liver. Only ER expression in the uterus was found to be greater in the CEE-treated group than in SERM-treated groups.

Animals↗
PubMed1999

Vagal afferents from the uterus and cervix provide direct connections to the brainstem.

Previous anatomical studies demonstrated vagal innervation to the ovary and distal colon and suggested the vagus nerve has uterine inputs. Recent behavioral and physiological evidence indicated that the vagus nerves conduct sensory information from the uterus to the brainstem. The present study was undertaken to identify vagal sensory connections to the uterus. Retrograde tracers, Fluorogold and pseudorabies virus were injected into the uterus and cervix. DiI, an anterograde tracer, was injected into the nodose ganglia. Neurectomies involving the pelvic, hypogastric, ovarian and abdominal vagus nerves were performed, and then uterine whole-mounts examined for sensory nerves containing calcitonin gene-related peptide. Nodose ganglia and caudal brainstem sections were examined for the presence of estrogen receptor-containing neurons in "vagal locales." Labeling of uterine-related neurons in the nodose ganglia (Fluorogold and pseudorabies virus) and in the brainstem nuclei (pseudorabies virus) was obtained. DiI-labeled nerve fibers occurred near uterine horn and uterine cervical blood vessels, in the myometrium, and in paracervical ganglia. Rats with vagal, pelvic, hypogastric and ovarian neurectomies exhibited a marked decrease in calcitonin gene-related peptide-immunoreactive nerves in the uterus relative to rats with pelvic, hypogastric, and ovarian neurectomies with intact vagus nerves. Neurons in the nodose ganglia and nucleus tractus solitarius were immunoreactive for estrogen receptors. These results demonstrated: (1) the vagus nerves serve as connections between the uterus and CNS, (2) the nodose ganglia contain uterine-related vagal afferent neuron cell bodies, and (3) neurons in vagal locales contain estrogen receptors.

Animals↗
PubMed1989

Comparison of in vivo bioavailability of progestational agents into the rat uterus and liver and the effect of plasma protein binding.

The in vivo bioavailabilities of three clinically available progestational agents were evaluated with a previously described rat model. With this model a single-injection, double-isotope technique was performed to calculate and compare the unidirectional extractions of progesterone, 19-nortestosterone, and medroxyprogesterone acetate into the rat uterus and liver. To assess the role of plasma protein binding in the extraction of these agents, steroids were presented in four different vehicles: (1) Ringer's solution, 0.1% bovine serum albumin; (2) Ringer's solution, 4% bovine serum albumin; (3) Ringer's solution, 0.8 mg/ml, alpha 1-acid glycoprotein; (4) human pregnancy serum. The results revealed that liver extraction always exceeded uterine extraction for each progestin, regardless of the vehicle, and that liver extraction was approximately 100% for all steroids. With regard to the uterus, when binding proteins were not present in the injectate, the extraction of the three steroids was similar; the uterine vasculature was relatively permeable to these progestins, and bovine serum albumin and alpha 1-acid glycoprotein had no major effect on the uptake into the uterus. However, when human pregnancy serum was in the injectate, the extractions of progesterone and 19-nortestosterone into the rat uterus were significantly diminished. In contrast, pregnancy serum had no effect on the uptake of medroxyprogesterone acetate into the uterus, with the extraction equal to that of Ringer's solution alone. This suggests that, regardless of potential binding proteins, medroxyprogesterone acetate displays greater bioavailability than that of the other progestogens studied.

Albumins↗
PubMed1995

An increase in expression of the lipocalin 24p3 is found in mouse uterus coincident with birth.

OBJECTIVE: To provide novel insights into the molecular events associated with parturition, a differential screen was made of a mouse uterine complementary deoxyribonucleic acid library to identify selectively expressed genes in late pregnancy. STUDY DESIGN: A differential hybridization was used to screen a mouse complementary deoxyribonucleic acid library prepared from late pregnancy uterus. A 1 kb clone was isolated that was subsequently identified as 24p3, a member of the lipocalin family. By use of radiolabeled complementary deoxyribonucleic acid probes prepared from this clone Northern hybridizations were conducted against total ribonucleic acid purified from mouse uterus collected during late pregnancy and the first week after birth and a variety of other mouse tissues to determine whether this gene is selectively expressed in the uterus coincident with parturition. RESULTS: Low levels of message for the 24p3 gene could be detected in uterine ribonucleic acid, but there was a massive increase in the level of message for this gene on the days surrounding birth. Northern hybridizations conducted against additional tissues collected from both pregnant and nonpregnant mice did not detect message to a similar degree as found in the uterus. CONCLUSIONS: The uterus constitutes a major site of expression of this gene, particularly near birth. The expression of this gene coincident with birth suggests a potential physiologic role of the neutrophil with the induction of labor.

Acute-Phase Proteins↗
PubMed1993

Effect of a pure nonsteroidal antiestrogen, CDRI-85/287, on implantation--associated histological and biochemical changes in the rat uterus.

The effect of compound CDRI-85/287, a pure, nonsteroidal antiestrogen, on implantation-associated changes in rat uterus were studied. Results provide a clear correlation between the antideciduogenic action of 85/287 (0.05 mg/kg in days 1-5 post-coitum or 2.5 mg/kg on day 1 post-coitum) and the time of its administration in relation to the secretion of prenidatory luteal phase estrogen. The antiestrogenic nature of the compound is further highlighted by inhibition of estradiol-induced increase in vascular permeability. In the present study, differences in the pattern of biochemical maturation of the pregnant, pseudopregnant and 85/287-treated rat uterus have also been illustrated. As compared to the pregnant rat uterus, absence of (the blastocyst and) decidualizing tissue in the pseudopregnant rat uterus accounts for the low uterine weight, protein, RNA, phospholipids and alkaline phosphatase at the time of implantation. Post-coital treatment with 85/287 (2.5 mg/kg, oral) inhibited increase in these parameters at the time of implantation. Glycogen levels which were lowered in the pregnant rat uterus on days 5 and 6, remain unaltered in the pseudopregnant and 85/287-treated rat uteri, suggesting nonutilization of this energy substrate. These findings provide sufficient evidence that the antiimplantation activity of 85/287 is due to its antiestrogenic property.

Alkaline Phosphatase↗
PubMed1992

Interleukin-1, interleukin-6, and tumor necrosis factor alpha are produced in the mouse uterus during the estrous cycle and are induced by estrogen and progesterone.

The ovarian steroids, estrogen and progesterone, regulate cellular and molecular changes which occur in the uterus during the estrous cycle. Cycles of protein synthesis, cell proliferation and differentiation, and cell death are the direct results of changes in hormone concentration. To explore the possibility that cytokines, which stimulate proliferation and differentiation of numerous types of cells, might be associated with those cyclic changes, the production of IL-1, IL-6, and TNF alpha was examined in the mouse uterus. Cytokine mRNA expression, bioactivity, and immunoreactivity were quantitated during the estrous cycle, following ovariectomy and exposure of ovariectomized mice to estrogen and progesterone. IL-1, IL-6, and TNF alpha mRNA was detected, and mRNA levels for each of the cytokines varied with the stage of the cycle. Cytokine bioactivity was expressed throughout the cycle, but levels of each cytokine were highest during proestrus and/or estrus. Immunoreactivity paralleled bioactivity. Uterus from ovariectomized mice contained little or no cytokine activity, and systemic administration of estrogen or progesterone resulted in the induction of IL-1 alpha and IL-1 beta mRNA expression. Significant amounts of IL-6 and TNF alpha mRNA appeared only following the exposure of ovariectomized mice to estrogen plus progesterone. Cytokine bioactivity and immunoreactivity also appeared following the administration of estrogen and/or progesterone. The highest activity levels for each cytokine were observed following the injection of estrogen plus progesterone. Cyclic expression of IL-1, IL-6, and TNF alpha in the uterus and their apparent regulation by estrogen and progesterone raise the possibility that cytokines and factors which are induced by cytokines are part of the regulatory process which is induced by ovarian hormones in the uterus of reproductive age females.

Animals↗