Estradiol Dipropionate Research Articles

Estrus Synchronization with Pseudopregnant Gilts Induced by a Single Treatment of Estradiol Dipropionate

The aims of this study were to determine whether a single treatment of estradiol dipropionate (EDP) could induce pseudopregnancy in gilts and to determine the effectiveness of PGF(2alpha) treatment on estrus synchronization in EDP-induced pseudopregnant gilts. In experiment 1, gilts were treated with 20 mg of EDP (n=11) or vehicle (n=5) on Day 12 (Day 0=onset of estrus). Establishment of pseudopregnancy was defined as a lack of estrus and maintenance of the plasma progesterone concentration above 1 ng/ml between Days 12 and 36. Nine of 11 gilts (82%) treated with EDP became pseudopregnant. The plasma estradiol-17beta level was significantly higher in the EDP-treated gilts than in the control gilts until Day 29. In experiment 2, PGF(2alpha) was administered twice with a 24-h interval from Day 36 in pseudopregnant gilts (n=6) or Day 10 in cyclic gilts (control; n=5). Estrus after PGF(2alpha) treatment was observed in 83% of the pseudopregnant gilts. The interval from the day of the first PGF(2alpha) treatment to the onset of estrus and the peak of the LH surge was significantly shorter in the pseudopregnant gilts than in the control gilts. In experiment 3, six pseudopregnant gilts were bred by artificial insemination at the estrus after PGF(2alpha) treatment. The farrowing rate and average litter size did not differ between the PGF(2alpha)-treated pseudopregnant and cyclic gilts. These results indicate that a single treatment of EDP on Day 12 of the estrous cycle can induce pseudopregnancy in pigs and that a convenient protocol for administering PGF(2alpha) to EDP-induced pseudopregnant pigs is available for estrus synchronization programs in cyclic pigs.

Effect of Estrogen-Receptor Interaction on the Levels of Fatty Acid-Binding Proteins and Spectra of Free Acids in Small Intestinal Mucosa of Rabbits

Data on the possibility of estrogens to regulate absorption of free fatty acids (FFA) during absorption of lipids in small intestine with associated estrogen-receptor interaction and changes in fatty acid-binding protein (FABP) levels are reported. In particular, characteristics of cytoplasmic estrogen receptors, estradiol metabolism, FABP levels and spectra of FFA in FABP fraction were studied in small intestinal mucosa of sexually mature and immature female rabbits, intact or after ovariectomy and estradiol dipropionate administration. The dissociation constants (Kd) and number of binding sites were determined in coordinates of Scatchard. FABP levels were demonstrated spectrophotometrically after ultracentrifugation (K-32M) and gel filtration (G-75). FFA composition of FABP fraction, chyme and enterocytes were analyzed by a chromatographic method (Tsvet-110). Levels of body estrogens were monitored by high-performance liquid chromatographic analysis (Tsvet-306) of estrogens in daily urine. The study has demonstrated a specific relation between FABP levels and their lipid component, FFA, on the one hand and endo- and exogenous estrogen levels on the other hand, in female rabbits maintained on a standard fat-free diet.

Effects of estradiol dipropionate on the biochemical composition of testis and accessory sex organs of adult rats.

A short term treatment of 14 days with estradiol dipropionate, ovocyclin¿ to adult male albino rats for 7 and 14 days in a dose of 2 mg/rat significantly inhibited the structural and functional integrity of the testis and accessory glands. The weights of these organs were significantly reduced. The activity of the enzymes acid and alkaline phosphatase and succinic dehydrogenase in testis and the concentration of sialic acids, fructose and citric acid in caput and cauda epididymides, prostate and seminal vesicles respectively were significantly lowered after both treatments. All these changes were found to be irreversible even on withdrawal of ovocyclin¿ for 28 days after 14 days treatment. On discussing the results with previous reports, it is proposed that estrogens probably impede the activity of these organs by inhibition of androgen production, their antiandrogenic nature or their direct action on these organs.

Biological action of estrogen on the epididymis of prepubertal rhesus monkey.

An estrogen binding protein has been demonstrated in the cytosol of the epididymis and caudal lobe of prostate of immature rhesus monkey. Scatchard plot analyses were linear, suggesting a single class of high affinity binding sites for the synthetic estrogen, R-2858 (Moxestrol) with a Kd of 5.88 X 10(-10) mol/l and a concentration of binding sites of 17.0 +/- 4.4 fmol/mg cytosol protein in the epididymis. In the prostate, the concentration of binding sites was 19.7 +/- 3.6 fmol/mg cytosol protein with a Kd of 5.42 X 10(-10) mol/l. In immature castrated monkeys, administration of estradiol dipropionate caused a significant increase in the weight, total protein and sialic acid content of the epididymis. This biological action of estrogen on the epididymis is presumably mediated via estrogen receptor.

Effects of chronic estradiol treatment on the thyroid gland structure and function of ovariectomized rats

BackgroundEstrogen therapy is widely used nowadays in women to treat many postmenopausal symptoms but it may have some undesirable effects due to multiple organs affection. So, the aim of this study was to determine the effects of chronic estradiol treatment on the structure and function of the thyroid gland in ovarictomized rats as a model simulating menopause.FindingsThirty adult female Wistar rats divided into three groups were used in this study; the first group was sham-operated, while the second and third groups were ovariectomized. The first and second groups were injected with olive oil while the third group was injected with estradiol dipropionate daily for three months, after that; hormonal assay for T3, T4, TSH and specimens of the thyroid were taken and processed to be examined by light and electron microscopy. The results of this study revealed that serum levels of T3 and T4 decreased in ovariectomized animals and significantly increased after estradiol treatment, while TSH increased in ovariectomized animals and decreased with estradiol treatment. Histological and morphometric study in ovariectomized group revealed marked accumulation of colloid in follicular lumens with decreased epithelial height in addition to increased connective tissue amount. After estradiol treatment the follicles became smaller in size, having small amount of colloid with increased epithelial height in addition to decreased connective tissue content. Ultrastructural study supported these results in addition to the presence of large amount of intracytoplasmic colloid vesicles after estradiol treatment.ConclusionLow estrogen level may lead to mild thyroidal hypofunction while estradiol treatment may lead to hyperactivity so it should be used very cautiously in the treatment of postmenopausal symptoms to avoid its undesirable stimulatory effect on the thyroid.

Effect of estradiol or calcium treatment on mammotrophs of female middle-aged rats

The effects of estradiol dipropionate (EDP) or calciumglucoheptonate (Ca) on the morphology and stereology of the PRLcellsin14-month-oldWistarfemaleratswerestudied.Theanimalsweretreated daily with EDP in the dose of 0.625 mg/kg b.w. or calciumglucoheptonate(Ca;11.4mg/kgb.w.)fortwoweeks.Thecontrolswereinjected with vehicle alone by the same schedule. Mammotrophs (PRLcells) were immunocytochemically localized by the PAP method. BloodPRL concentration was determined by Delfia procedure. In animalstreated with EDP the volume of both, PRL cells and their nuclei, as wellas the volume densities were significantly (p 0.05) decreased compared to control rats. Serum concentration ofPRL was significantly increased (p 0.05) changed by 2% compared to controls. Based on theseresults, it can be concluded that EDP expresses a strong stimulatoryeffect on the morphology and function of pituitary PRL cells.Keywords:PRL,mammotrophs,estradiol,calcium,middle-aged,female rats

Immunoreactive TSH cells in juvenile and peripubertal rats after estradiol and human chorionic gonadotropin treatment

Different hormones and growth factors control the homeostasis of the anterior pituitary gland. We examined the morphological features of pituitary thyroid stimulating hormone (TSH)-producing cells in juvenile and peripubertal female rats after treatments with estradiol-dipropionate (EDP), human chorionic gonadotropin (hCG) and a combination of both hormones (EDP+hCG). TSH-producing cells were labelled using a peroxidase-antiperoxidase immunohistochemical procedure for binding of a rabbit anti-rat beta-thyrotropic polyclonal antisera. Morphometric differences in the cytoplasmic and nuclear volume densities in thyrotropes after the treatments were determined using a stereological method. The relative weights of the pituitary glands were significantly higher in the EDP- and EDP+hCG-treated juvenile and peripubertal rats than in untreated age-matched controls. Treatment with EDP promoted a decrease, and treatment with hCG an increase, of the cellular and nuclear volumes in TSH cells in both juvenile and peripubertal females in comparison with the respective controls. Treatment with a combination of EDP+hCG did not induce any significant changes. The cytoplasmic and nuclear volume densities in TSH cells in the EDP+hCG-treated group were significantly higher than in the EDP-treated, and significantly lower than in hCG-treated rats at both growth stages. These findings suggest that estradiol and hCG exerted opposite effects on pituitary TSH-immunoreactive cells. The observed effects on thyrotrope morphology were apparently independent of the stage of development.

Effects of ovariectomy and chronic estradiol administration on pituitary–thyroid axis in adult rats

The effects of ovariectomy (Ovx) and of ovariectomy followed by chronic estradiol dipropionate administration (Ovx EDP) on the structure and function of the pituitary–thyroid axis were examined in the rat. Pituitary TSH cells and thyroid tissue were histologically, immunohistochemically and stereologically investigated. Serum TSH and T 4 levels were determined by RIA. Ovx did not affect pituitary weight, but subsequent treatment with EDP led to its more than two-fold increase ( p < 0.05). After ovariectomy, the cellular volume of pituitary TSH-immunoreactive cells increased by 28%, p < 0.05 compared to sham-operated animals (SO). Treatment of Ovx rats with EDP partially reversed this change. However, the relative volume density of thyrotrophs decreased in comparison to the Ovx and SO groups (by 18% and 23%, p < 0.05, respectively). No statistically significant differences in serum TSH levels were observed between the experimental groups. In thyroid tissue both peripheral and central follicles responded to Ovx and EDP treatments. Compared to SO rats, the relative volume densities of the follicles and colloid were increased (by 14% and 30%, p < 0.05, respectively) in Ovx rats. Chronic EDP treatment of Ovx rats reversed these changes to the pre-ovariectomy state. Hyperplasia of thyroid follicular cells and a significant reduction (by 21%, p < 0.05) of the serum level of T 4 were detected. In conclusion, estradiol deficiency and chronic treatment affected pituitary TSH cells and thyroid tissue. The sum effect of Ovx on the pituitary–thyroid axis was slightly stimulatory. Subsequent EDP treatment decreased thyroid functioning but at the same time preserved serum TSH at the control level.

Kinetics of bromhexine-mediated down-regulation of focal adhesive molecules of uterus and trophectoderm affecting conception in the rat

Purpose Quantitative evaluation of properties of bromhexine (B) for expression of uterine proteins in ovariectomized (OVX) and pregnant rats. Materials and Methods Expression of proteins through SDS-PAGE, along with incorporation of glycosidic moieties, was conducted in pregnant and OVX rats under B influence. These findings were corroborated with other tests such as implantation sites, fetal and litter sizes in pregnant rats. Results In OVX animals, even under the influence of estradiol dipropionate and progesterone, the B recreated a condition akin to OVX animals. It also induced 50–80% inhibition in the incorporation of glycosidic moieties to polypeptide chain. Distinct reduction in implantation sites, fetal sizes and interference in the conception (16/46) in pregnant rats substantiated the results of the action of B as an antiimplantation agent. Conclusion Bromhexine has shown interference in blastocyst attachment, conception, reduction in number of implantation sites and dwarfing of fetuses; hence, it is a potential candidate for antiimplantation.

The effects of estrogen on the morphology of the pyramidal neurons of the parietal cortex of female rats

In this study the effects of a neonatally (3rd day of life) administered single dose (1 mg) of estradiol dipropionate (E2) on the parietal cortex of juvenile (16 days of life) female rats were investigated. The morphology the volume of the soma and the thickness of the apical dendrite were studied in Golgi impregnated pyramidal neurons from both the external and internal pyramidal layers. In the treated female rats the volume of the soma and the thickness of the apical dendrite of pyramidal neurons was increased surpassing the values in the corresponding controls. These findings indicated significant and prolonged effects of a single dose of estrogen administered in the neonatal period, on the parietal neocortical pyramidal neurons of female rats.

Estradiol-Dependent Effect of Nitric Oxide on Meiotic Maturation of Mouse Oocytes

Estradiol dipropionate decreased the number of oocytes in mouse ovary and suppressed meiotic maturation of these cells. Administration of NO donors sodium nitroprusside and S-nitroso-N-acetylpenicillamine increased the ability of ovarian oocytes to complete meiotic maturation and counteracted the effect of estradiol dipropionate. Our results suggest that estradiol is involved in the regulation of production and release of ovarian NO.

Effects of histone deacetylase inhibitors on estradiol-induced proliferation and hyperplasia formation in the mouse uterus

It is suggested that estrogen hormones recruit mechanisms controlling histone acetylation to bring about their effects in the uterus. However, it is not known how the level of histone acetylation affects estrogen-dependent processes in the uterus, especially proliferation and morphogenetic changes. Therefore, this study examined the effects of histone deacetylase blockers, trichostatin A and sodium butyrate, on proliferative and morphogenetic reactions in the uterus under long-term estrogen treatment. Ovari-ectomized mice were treated with estradiol dipropionate (4 microg per 100 g; s.c., once a week) or vehicle and trichostatin A (0.008 mg per 100 g; s.c., once a day) or sodium butyrate (1% in drinking water), or with no additional treatments for a month. In animals treated with estradiol and trichostatin A or sodium butyrate, uterine mass was increased, and abnormal uterine glands and atypical endometrial hyperplasia were found more often. Both histone deacetylase inhibitors produced an increase in the numbers of mitotic and bromodeoxyuridine-labelled cells in luminal and glandular epithelia, in stromal and myometrial cells. Levels of estrogen receptor-alpha and progesterone receptors in uterine epithelia, stromal and myometrial cells were decreased in mice treated with estradiol and trichostatin A or sodium butyrate. Expression of beta-catenin in luminal and glandular epithelia was attenuated in mice treated with estradiol with trichostatin A or sodium butyrate. Both histone deacetylase inhibitors have similar unilateral effects; however the action of trichostatin A was more expressed than that of sodium butyrate. Thus, histone deacetylase inhibitors exert proliferative and morphogenetic effects of estradiol. The effects of trichostatin A and sodium butyrate are associated with changes in expression of estrogen receptor-alpha, progesterone receptors and beta-catenin in the uterus.

Estradiol and calcium affect the growth hormone producing cells in female middle-aged rats

The effects of multiple doses of estradiol dipropionate (EDP) or calcium glucoheptonate (Ca) on the growth and function of pituitary somatotropes (GH cells) were studied. Female middle-aged rats were receiving i.p. EDP (0.625 mg i.p./kg b.w), or Ca (11.4 mg/kg b.w) every day for two weeks. Blood samples were collected for hormone analyses and pituitaries dissected for histological and morphometric evaluation 24 h after the last injection. GH-producing cells were examined using the peroxidase-antiperoxidase (PAP) immuno-histochemical procedure. Both EDP- and Ca-treatment significantly decreased all morphometric parameters of GH cells (p<0.05) in comparison with the corresponding controls. Serum concentration of growth hormone (GH) in EDP- or Ca-treated groups was lower by 65% and 13% (p<0.05) respectively comparing to the controls. The difference between all morphometric parameters of EDP- and Ca-treated rats was statistically significant (p<0.05) in relation to the controls. These findings suggest that multiple EDP, or Ca application affects (directly or indirectly) the control of growth and secretory activity of GH cells in middle-aged female rats.

Chronic Estradiol Exposure Modulates Thyroid Structure and Decreases T4 and T3 Serum Levels in Middle-Aged Female Rats

Objectives: In human medicine, estrogen is applied in prevention and treatment of health problems associated with the menopause. The aim of this study was to examine the effects of chronic estradiol dipropionate (EDP) treatment on thyroid gland structure and function in middle-aged female rats. Methods: At 14 months of age, Wistar rats received 0.625 mg EDP/kg b.w./day intraperitoneally for 2 weeks. The peripheral and central zones of the thyroid were stereologically analyzed and the following morphometric parameters determined: volume density of follicles, follicular epithelium, interstitium and colloid, epithelial height and the index of activation rate. Serum levels of TSH, T₄ and T₃ were determined by ELISA. Results: EDP treatment led to significant decreases in volume densities of follicles and follicular epithelium, epithelial height and index of activation rate (by 11%, p < 0.05; 23%, p < 0.005; 11%, p < 0.05 and 21%, p < 0.05, respectively) in comparison to control values. Hyperplasia of thyroid follicular cells was noticed in 25% of EDP-treated animals. Serum levels of T₄ and T₃ were decreased (by 33%, p < 0.005 and 28%, p < 0.001, respectively), but TSH concentration was not significantly different from that of the controls. Conclusion: Chronic estradiol treatment significantly decreased volume density and height of centrally located follicular epithelium, follicular activation index and serum level of total thyroid hormones in middle-aged rats.

Synthesis and Estrogenic Activity Screening of Some 6,9-Disubstituted Estradiol Derivatives

Oxidation of estradiol dipropionate (1) with chromium(VI) oxide-3,5-dimethylpyrazole complex yielded 9α-hydroxy-6-oxoestra-1,3,5(10)-triene-3,17β-diyl dipropionate (2) and 6-oxoestra-1,3,5(10)-triene-3,17β-diyl dipropionate (3). Dehydration of compound 2 with phosphorus(V) oxide or acetic anhydride gave 6-oxoestra-1,3,5(10),9(11)-tetraene-3,17β-diyl dipropionate (5). Reduction of compounds 2 and 5 with sodium borohydride afforded 3,6β,9α-trihydroxyestra-1,3,5(10)-triene-17β-yl propionate (4) and 3,6β-dihydroxyestra-1,3,5(10),9(11)-tetraene-17β-yl propionate (6), respectively. The action of thionyl chloride on compound 2 yielded 6-hydroxyestra-1,3,5(10),6,8-pentaene-3,17β-diyl dipropionate (7). Biological tests in vivo of these compounds showed a moderate antiestrogenic activity of compound 4.

Effects of peroxisome proliferator activated receptors-alpha and -gamma agonists on estradiol-induced proliferation and hyperplasia formation in the mouse uterus.

It is suggested that the action of peroxisome proliferator-activated receptors (PPARs) cross-talks with estrogen signaling in the uterus. However, it is not known how PPAR agonists affect estrogen-dependent processes in the uterus, especially proliferation and morphogenetic changes. The effects of agonists of PPAR-alpha and -gamma on proliferative and morphogenetic reactions in the uterus under short- and long-term estrogen treatments were therefore examined. Ovariectomized mice were treated with estradiol dipropionate (4 micro g/100 g, s.c., once a week) or vehicle and rosiglitazone (PPAR-gamma agonist) or fenofibrate (PPAR-alpha agonist) or with no additional treatment for 2 days or for 30 days. Treatment with estradiol and PPAR agonists for 2 days did not affect uterine mass. In mice treated with estradiol and rosiglitazone for 2 days, proliferation was enhanced and levels of estrogen receptors-alpha and beta-catenin were decreased in all uterine tissues. Treatment with estradiol and fenofibrate for 2 days had the opposite effects on the parameters tested. In animals treated with estradiol and rosiglitazone for 30 days, uterine mass was increased, abnormal uterine glands and atypical endometrial hyperplasia were found more often and levels of estrogen receptors-alpha and beta-catenin were decreased. In animals treated with estradiol and fenofibrate for 30 days, uterine mass was decreased, most of the uterine glands had a normal structure, no cases of atypical hyperplasia were diagnosed, proliferative activity was declined and the levels of estrogen receptors-alpha and beta-catenin were markedly higher. Treatment with rosiglitazone or fenofibrate did not affect the serum estradiol level in the mice which received estradiol together with PPAR agonists for 30 days. Thus, rosiglitazone exerted the proliferative and morphogenetic effects of estradiol, but fenofibrate had the opposite effect. The actions of rosiglitazone and fenofibrate are associated with changes in the expression of estrogen receptors-alpha and beta-catenin in the uterus.

Lithium treatment enhances estradiol-induced proliferation and hyperplasia formation in the uterus of mice

Objectives: It is suggested that the Wnt/β-catenin pathway plays a role in the regulation of estrogen action in the uterus. However, this suggestion has not been proved. Lithium can mimic increased activity of the Wnt/β-catenin pathway by blocking the activity of glycogen synthase kinase-3β. There are no data on the effects of lithium on estrogen-dependent processes in the uterus. This work was therefore aimed to examine the action of lithium on proliferative and morphogenetic reactions in the uterus under short- and long-term estrogen treatments. Study design: Ovariectomized mice received estradiol dipropionate (2 μg per 100 g; s.c.) once a week or vehicle and drank tap water with 0.05% lithium chloride or plain tap water for 2 or 30 days. Results: In animals treated with estradiol and lithium for a month, the incidence of atypical endometrial hyperplasia was significantly higher. In animals treated with estradiol and lithium for 2 days or for a month, uterine mass, the number of mitotic cells and BrdU-labelled cells in luminal epithelium, glandular epithelium, stromal and myometrial cells was markedly greater, whereas the levels of estrogen receptors-α, β-catenin and glycogen synthase kinase-3β were markedly lower in all uterine compartments, than in those in mice received estradiol with no lithium to drink. Conclusions: Lithium treatment results in an increase in estradiol-induced proliferative and morphogenetic changes in the uterus. This action of lithium is associated with decreased expression of estrogen receptors-α, β-catenin and glycogen synthase kinase-3β in the uterus.

The thyroid C cells of ovariectomized rats treated with estradiol.

The structure and function of thyroid C cells were studied in ovariectomized (Ovx) adult female rats without and after chronic treatment with estradiol dipropionate (EDP). A peroxidase-antiperoxidase method was applied for localization of calcitonin (CT) in the C cells. Morphometric changes in their volume, nuclei, and relative volume density were evaluated in comparison with sham-operated control rats using a stereological method. The number of C cells was calculated. CT content in the sera was determined by radioimmunoassay. Ovariectomy (Ovx) led to a 21% increase in body weight ( P<0.005), while treatment of Ovx rats with EDP decreased body weight by 25% ( P<0.01). The immunoreactivity for CT in C cells of the Ovx rats was markedly increased. Significant decreases in the volume of C cells (by 13%; P<0.05) and serum CT (by 45%) were recorded, while the C cell number increased by 59% ( P<0.05) in relation to the corresponding controls. The treatment of Ovx rats with EDP caused conspicuous degranulation of the C cells. The cellular volume was increased by 11% and serum CT by 36% in comparison with Ovx animals. At the same time a decrease in C cell number by 29% ( P<0.05) was evident. It may be concluded that estradiol deficiency after Ovx reduced the synthesis and release of CT, while chronic treatment of these animals with EDP had a positive effect on the secretory activity of thyroid C cells.

Influence of sex and estrogen on vitamin D‐induced arterial calcification in rats

Background: It is known that the process of arteriosclerosis is affected by sex and estrogen. The present study was thus undertaken to examine the effects of these factors on arterial calcification, a form of arteriosclerosis, using a rat model of vitamin D toxicity.Methods and results: Vehicle or 5 µg/kg per day 1α(OH)D3 was given to male and female 30‐week‐old Fisher rats for 2 weeks. Arterial calcification, evaluated by calcium content in the aorta, was 70% more marked in male rats compared to that in female rats, whereas calcium content in the aorta was similar in vehicle‐treated male and female rats. Next, the effects of ovariectomy and estrogen replacement (estradiol dipropionate 20 µg/kg per week) were examined in female rats given 5 µg/kg per day 1α(OH)D3 for 2 weeks. Calcium content in the aorta was significantly higher in ovariectomized rats than in sham‐operated rats and in ovariectomized and estrogen‐replaced rats. No difference between the groups was seen when vehicle was given to the animals.Conclusions: These results suggest that sex and estrogen can modify the process of arterial calcification. The mechanisms remain to be determined, although the effects were independent of serum calcium level.

Uterine response to estradiol under action of chorionic gonadotropin in mice

This work examined the effect of chorionic gonadotropin on proliferative and morphogenetic reactions in the uterus under short- and long-term estrogen treatments. Ovariectomized mice received a single injection with estradiol dipropionate (2 μg per 100 g; subcutaneously, sc) or vehicle and injections with human chorionic gonadotropin (10 IU per 100 g; sc) or vehicle twice a day for 2 days. Other groups of animals received injections with estradiol once a week or vehicle and injections with chorionic gonadotropin or vehicle once a day for 30 days. The uteri were removed 48 h after the last estradiol or vehicle injection. In animals treated with estradiol and chorionic gonadotropin for a month, the incidence of atypical endometrial hyperplasia was significantly higher. In animals treated with estradiol and chorionic gonadotropin for 2 days or for a month, uterine mass was slightly increased, the number of mitotic cells and BrdU-labeled cells was greater in luminal epithelium, glandular epithelium, stromal and myometrial cells, whereas the expression of estrogen receptors-α was lower in all uterine compartments, than in control. In mice who received estradiol and chorionic gonadotropin for 2 days, levels of β-catenin and glycogen synthase kinase-3β in luminal and glandular epithelia were lower. In animals treated with estradiol and chorionic gonadotropin for a month, the level of β-catenin was slightly higher, and the expression of glycogen synthase kinase-3β was lower in luminal and glandular epithelia. Thus, chorionic gonadotropin exerts estradiol-induced proliferative and morphogenetic changes in the uterus. This action of chorionic gonadotropin is associated with decreased expression of estrogen receptors-α and with changes in expression of β-catenin and glycogen synthase kinase-3β in the uterus.