Mature Uterus Research Articles

Results of ligation the internal iliac and ovarian arteries in the experiment

Objective: to study in an experiment on animals pathomorphological changes in the tissues of the uterus, appendages and blood vessels after ligation of the internal iliac and ovarian arteries.Materials and methods: An experiment was conducted with 6 mature pigs. Group I (n=3) consisted of intact pigs without surgery, group II (n=3) included animals with ligation of the internal iliac and ovarian arteries on both sides. 12 months after the operation, slaughter was performed and the organo-complex of the uterus with appendages and iliac vessels was taken for electron microscopic pathomorphological examination.Results: comparative results of the study of the uterus, appendages found that the normal structure of the mature uterus was preserved, there were no changes in the structure of the fallopian tubes, tissues and vessels of the ovaries. All changes were found in the area of ligation of the ovarian and internal iliac arteries, although the arteries retained their lumen, but were deformed and surrounded by dense fibrous connective tissue. Conclusion: ligation of the ovarian and internal iliac arteries with absorbable suture material causes only local changes. The sufficiency of collateral blood flow is confirmed by the absence of atrophy of the uterus, fallopian tubes and ovaries, as well as organ deformities.

Pubertal induction in girls with Turner Syndrome.

Turner Syndrome (TS) is the most common female sex chromosome aneuploidy in females, and patients may present with hypergonadotropic hypogonadism due to gonadal dysgenesis. Timing and modalities of pubertal induction in these patients is still a matter of debate. Aim of this review was to focus on the latest update on pubertal induction in TS. Based on literature data, the following practical approach to this issue is recommended. Pubertal induction should begin between 11 and 12 years of age, starting with low doses of estradiol to preserve height potential. Transdermal 17β-Estradiol (17β-E2) could represent the first-choice induction regimen as it is more physiologic compared to an oral regimen and avoids the first-pass mechanism in the liver. In the case of poor compliance, administration of oral 17β-E2 or ethinyl estradiol could be offered. Incremental dose increases, approximately every 6 months, can contribute to mimic normal pubertal progression until adult dosing is reached over a 2- to 3-year period. Progestin should be added once breakthrough bleeding occurs or after 2 to 3 years of estrogen therapy or if ultrasound shows a mature uterus with thick endometrium. Treatment needs to be individualized and monitored by clinical assessment in relation to patient compliance and satisfaction. Well-designed prospective randomized clinical trials aimed to identify the best estrogen regimen for pubertal induction in TS girls are needed.

Uterine Development During Induced Puberty in Girls with Turner Syndrome.

ObjectiveMost girls and women with Turner syndrome (TS) require estrogen replacement therapy (ERT) to initiate or maintain pubertal development. Most likely, the most fundamental effect of ERT in hypogonadism is the promotion of uterine growth. The optimal ERT model is still being discussed. The present study aimed to assess uterine size in girls with TS in the prepubertal state during and after the induction of puberty and compare it to a healthy population.MethodsThe analysis encompassed 40 TS girls. The prepubertal and postpubertal control groups contained 20 healthy girls each. All patients with TS were treated with 17-ß estradiol. Uterine imaging was performed with two-dimensional (2D) transabdominal ultrasound. The uterine volume (UV) and fundocervical antero-posterior ratio (FCR) were calculated in patients with TS before the pubertal induction, after 6-12 months of estrogen replacement therapy (ERT), after ≥ 36 months of ERT or ≥ 12 months after menarche.ResultsThe average age of TS patients at estrogen introduction and at the last control visit, when the uterus was considered mature, was 12.9 years and 16.1 years, respectively. The UV in patients with TS at the beginning of ERT was 1.55 ± 1.22 cm3 and was not significantly different from the UV in the prepubertal controls. The mature UV in patients with TS was 31.04 ± 11.78 cm3 and was significantly smaller than the UV of the postpubertal controls (45.68 ± 12.51 cm3, p<0.001). The FCR in girls with TS did not differ significantly from that in the prepubertal and postpubertal control groups, respectively. No prognostic factors could be established for the final UV. By the last control visit, thelarche had advanced in most patients to Tanner 4 and 5 (37.5% and 40%, respectively).ConclusionsBefore the onset of ERT, patients with TS have a uterus similar in size to that in prepubertal healthy girls. Pubertal induction in patients with TS causes a significant increase in the UV that is detectable after 6-12 months of ERT. The mature uterus is smaller in patients with TS than in the age-matched healthy population.

Pubertal induction in girls with Turner syndrome

Turner Syndrome (TS) is the most common female sex chromosome aneuploidy in females, and patients may present with hypergonadotropic hypogonadism due to gonadal dysgenesis. Timing and modalities of pubertal induction in these patients is still a matter of debate. Aim of this review was to focus on the latest update on pubertal induction in TS. Based on literature data, the following practical approach to this issue is recommended. Pubertal induction should begin between 11 and 12 years of age, starting with low doses of estradiol to preserve height potential. Transdermal 17β-Estradiol (17β-E2) could represent the first-choice induction regimen as it is more physiologic compared to an oral regimen and avoids the first-pass mechanism in the liver. In the case of poor compliance, administration of oral 17β-E2 or ethinyl estradiol could be offered. Incremental dose increases, approximately every 6 months, can contribute to mimic normal pubertal progression until adult dosing is reached over a 2- to 3-year period. Progestin should be added once breakthrough bleeding occurs or after 2 to 3 years of estrogen therapy or if ultrasound shows a mature uterus with thick endometrium. Treatment needs to be individualized and monitored by clinical assessment in relation to patient compliance and satisfaction. Well-designed prospective randomized clinical trials aimed to identify the best estrogen regimen for pubertal induction in TS girls are needed.

Ultrastructural study of uterine epithelium in the domestic cat during prenatal development

The study describes the sequence of ultrastructural changes of the endometrial lining epithelium, first in the primordial paramesonephric ducts, then in the differentiating uterine horns, and finally in the mature uterus. The research material comprised female fetuses of the domestic cat, aged 33–63 days post conceptionem (p.c.), and mature females. The ultrastructural observations of the developing epithelium were conducted using transmission electron microscopy (TEM) and light microscopy (LM). The results revealed two basic stages in the development of the uterine mucosal epithelium in the domestic cat: the development of the epithelium of the uterine segment of the paramesonephric ducts, lasting from day 33 to day 42 p.c., and the differentiation of this epithelium into the mucosal epithelium of the uterus, starting after day 42 p.c. and lasting until the end of the prenatal period. The epithelium of the uterine segments of the paramesonephric ducts is pseudostratified with a flat surface, all cells being characterized by the same distribution of desmosomes, ribosomes, rough endoplasmic reticulum (rER) cisternae, and mitochondria in the cytoplasm. The differentiating epithelium of the uterus after day 51 p.c. is pseudostratified with a varied height. In the epithelial cells there are increases of (i) the number and complexity of the junctional complexes, (ii) the number of invaginations of the lateral cell membranes, and (iii) the number of elongated mitochondria, and also there appear distended cisternae of the rER, lipid droplets and clusters of glycogen, which suggest increasing metabolism and secretory activity of the cells during the transformation of the epithelium.

A tissue-specific enhancer of the C. elegans nhr-67/tailless gene drives coordinated expression in uterine stem cells and the differentiated anchor cell

The nhr-67 nuclear receptor gene of Caenorhabditis elegans encodes the ortholog of the Drosophila tailless and vertebrate Tlx genes. In C. elegans, nhr-67 plays multiple roles in the development of the uterus during L2 and L3 larval stages. Four pre-VU cells are born in the L2 stage and form the precursor complement for the ventral surface of the mature uterus. One of the four pre-VU cells becomes the anchor cell (AC), which exits the cell cycle and differentiates, while the remaining three VU cells serve as stem cells that populate the ventral uterus. The nhr-67 gene functions in the development of both VU cell lineages and AC differentiation. Hypomorphic mutations in nhr-67 identify a 276bp region of the distal promoter that is sufficient to activate nhr-67 expression in pre-VU cells and the AC. The 276bp region includes 8 conserved potential cis-acting sites, including two E boxes and a nuclear receptor binding site. Mutational analysis demonstrates that the two E boxes are required for expression of nhr-67 in uterine precursor cells. The E/daughterless ortholog HLH-2 binds these sites as a homodimer, thus playing a central role in activating nhr-67 expression in the uterine precursors. At least two other binding activities, one of which may be the nhr-25/Ftz-F1 nuclear receptor transcription factor, also contribute to uterine precursor cell expression. The organization of the nhr-67 uterine precursor enhancer is compared to similar conserved enhancers in the egl-43, lag-2, and lin-3 genes, which contain the same HLH-2-binding E boxes and are similarly expressed in both pre-VU cells and the AC. This basic regulatory module allows the coordinated expression of at least four genes. Expression of genes in different cells that must coordinate to form a mature organ is driven by a shared set of promoter elements, which integrate multiple transcription factor inputs.

Pseudohypoparathyroidism: phenotypic spectrum in kindred

Pseudohypoparathyroidism (PHP) encompasses a heterogeneous group of disorders due to an inactivating mutation in the GNAS gene which encodes the α subunit of Gs proteins (Gsα). Gsα plays a crucial role in intracellular signal transduction of peptides, hormones and neurotransmitter receptors in multiple tissues. Key features of PHP include Albright Hereditary Osteodystrophy (AHO) and biochemical evidence of multiple hormone resistances. There are several conflicting mechanisms for its heterogeneity; a possible explanation is a tissue-specific differential imprinting of Gsα protein. PHP type1a has AHO with multiple hormone resistance and is inherited as maternal imprinting defect. PHP type 1b presents with hormone resistance but no AHO features and is probably due to epigenetic methylation defects. Peudopseudohypoparathyroidism is another subtype with AHO but absence of hormone resistance and is inherited as paternal inactivating mutation. We describe a family with female members having PHP with variable clinical and biochemical features. Two female siblings from non-consanguineous parents, patient A (15 year) & patient B (13 year) presented at birth with raised TSH levels and were diagnosed to have congenital hypothyroidism and treated with thyroxine replacement. Patient A was noted to have infantile obesity with short stature and evolving phenotypic features consistent with AHO. Further history revealed that her sister patient B has similar phenotypic appearance and was confirmed on clinical exam. Biochemical evaluation for Patient A showed a borderline low calcium and normal phosphate level with elevated PTH while Patient B had normal calcium and phosphate levels with high PTH. Both patients entered puberty at 11 years and patient A progressed to breast tanner 4 but has no menarche at 15 years despite pubertal gonadotropin levels (Table ​(Table1),1), advanced bone age (18 years) & mature uterus. Patient B is currently 12.5 years old and has progressed to tanner 3 breasts with no menarche. Mother exhibits features of AHO without hormone resistance. The father and younger brother do not have any features of AHO. Table 1 The two patients with PHP described above had an interesting presentation as congenital hypothyroidism with features of AHO evolving later in life. They exhibit clinical evidence of maternal transmission with end-organ resistance. This family illustrates heterogeneity of presentation of GNAS mutation. Written informed consent was obtained from the patients for publication of this abstract. A copy of the written consent is available for review by the Editor of this journal.

Uterine development in patients with Turner syndrome: Relation to hormone replacement therapy and karyotype

Our study aimed to assess uterine development in Turner syndrome patients and its relation to dose and type of estrogen therapy; and karyotype. Pelvic ultrasound was used to assess uterine size and shape, and ovarian volume in 40 Turner syndrome patients. Information on hormone replacement therapy was collected from patients' notes. Among the 40 patients studied, 57.5% started estrogen therapy and 30% were taking progestins. Sixty-five per cent had immature uterus, 17.5% had fully mature uterus and 17.5% had transitional uterus. Uterine volume was associated with age (p < 0.001), height (p = 0.002), weight (p = 0.001), years of estrogen use (p < 0.001), estrogen dose (p = 0.016), current estrogen use ( p =0.001) and Tanner breast stage ( p <0.001). Uterine volume was not affected by the type of estrogen used ( p =0.40) and karyotype ( p =0.40). Patients with Turner syndrome treated with estrogen (of adequate dose and duration) may attain a normal, mature uterine size and configuration, even at a late start of hormone replacement therapy and regardless of karyotype.

The influence of the female sex hormones on the response of the pig uterus to electrical stimulation

Abstract The response of the pig myometrium to electrical stimulation in vitro was used to assess the influence of the female sex hormones at different stages of the oestrus cycle. Optimal stimulation produced greater tension in the mature uterus than in the immature uterus and the tension was greater in the oestrogen-dominated uterus than in the progesterone-dominated uterus. The minimum (threshold) voltage necessary to elicit an isometric contraction was not influenced by the stage of the uterus in the oestrus cycle. Varying the frequency of stimulation caused changes in tension indicating the predominant sex hormone. The progesterone-dominated myometrium appears to bind calcium more strongly than the oestrogen-dominated myometrium.

Conjugated Oral versus Transdermal Estrogen Replacement in Girls with Turner Syndrome: A Pilot Comparative Study

The optimal route of estrogen replacement in Turner syndrome (TS) is unknown. The objective of the study was to compare conjugated oral vs. transdermal estrogen (TD E2) on bone accrual, uterine growth, pubertal development, IGF-I, and lipids in girls with TS. Prepubertal GH-treated girls aged 10 yr or older with TS were eligible. Subjects were randomized to conjugated oral estrogen or TD E2 for 1 yr. Assessments included dual-emission x-ray absorptiometry, pelvic ultrasound, Tanner staging, growth velocity, IGF-I, and lipid profile. Twelve girls (14.0 +/- 1.7 yr) were enrolled. TD E2 resulted in a significantly greater change in spine bone density at 12 months compared with conjugated oral estrogen (bone mineral content 9.0 +/- 0.9 vs. 5.8 +/- 0.9 g, P = 0.04; bone mineral density 0.12 +/- 0.01 vs. 0.06 +/- 0.01 g/cm2, P = 0.004; Z-score 0.7 +/- 0.1 vs. 0.3 +/- 0.1, P = 0.03). Greater increases in uterine length (4.13 +/- 0.39 vs. 1.98 +/- 0.39 cm, P = 0.003) and volume (22.2 +/- 4.4 vs. 4.0 +/- 4.4 ml, P = 0.02) were also found in the TD vs. the oral group at 1 yr. At study end, 66% of subjects in the TD group had a mature uterus vs. 0% in the oral group. No significant differences in other parameters examined were seen. In girls with TS, TD E2 resulted in faster bone accrual at the spine and increased uterine growth compared with conjugated oral estrogen. This pilot study provides preliminary information for optimizing estrogen replacement in this population.

Gestational morphogenesis of the uterine epithelium of the gummy shark (Mustelus antarcticus)

Developing embryos of the non-placental, viviparous gummy shark (Mustelus antarcticus) are supplied with yolk from external and internal yolk sacs throughout the initial stages of gestation. Yolk supplies are exhausted by the 7th month of an 11-12 month gestation. During embryonic development, there is an approximate 800% gain in dry mass. These factors suggest nutrients are transferred from the mother to the young. The results of the present study provide some insights into how this is occurring. The uteri are paired and both are functional. Using both light and transmission electron microscopy, regions of the uterus were examined throughout maturation and gestation. The layers of the uterine wall throughout the entire length are similar to the uteri of other chondrichthyans previously examined. The uterine epithelium of the body of the uterus is smooth contoured, does not form villi, and undergoes cyclical and secretory changes throughout maturity and gestation. In immature uteri, the epithelium is simple columnar with minimal periodic acid-Schiff-positive and Alcian blue-positive secretory vesicles. In mature uteri, the epithelium is highly stratified with cuboidal cells containing numerous Alcian blue-positive and periodic acid-Schiff-positive vesicles. With pregnancy, prominent changes include a reduction in the number of cell layers, a reduction in cell size, a reduction in the connective tissue intervening between epithelium and blood vessel endothelium, and an increase in blood vessel number and size, so that at term, the uterine compartment consists of a single layer of squamous cells immediately underlain by sinusoidal-like blood vessels. These features along with a small number of secretory vesicles, dilated intercellular spaces, and clear transport vesicles suggest the transepithelial transfer of water and minerals from the maternal to embryonic environment, supplemented by minimal uterine secretions. This is defined as minimal histotrophy and this article represents the first detailed description of this reproductive mode.

Comparison of Estrogen Responsive Genes in the Mouse Uterus, Vagina and Mammary Gland

Female reproductive organs are mainly regulated by estrogen and progesterone. Specifically, the uterus, vagina and mammary gland show organ-specific mitosis and morphological changes during proliferative events, such as estrous cycle, gestation and lactation. The mechanism underlying these organ-specific estrogen-dependent events is still unknown. We examined, therefore, global gene expression in the mature uterus, vagina and mammary gland of ovariectomized adult mice 6 hr after an injection of 5 microg/kg 17beta-estradiol (E2) using a microarray method in order to identify primary E2-responsive genes. Half of the E2 up-regulated genes in the uterus were similar to those in the vagina. E2 up-regulated the expression of Insulin-like growth factor 1 (Igf-1) genes in the uterus and vagina. In the vagina, E2 up-regulated the expression of IGF binding proteins (Igfbp2 and Igfbp5). In the mammary gland, unlike the uterus and vagina, no gene showed altered expression 6 hr after the E2 exposure. These results suggest that expression of Igf-1 and morphogenesis genes is regulated by E2 in an organ-specific manner, and it is supported by the results of BrdU labeling showing E2-induced mitosis in the uterus and vagina except the mammary gland. The differences in organ specificity in response to E2 may be attributed by differences in gene expression regulated by E2 in female reproductive organs. The candidate estrogen-responsive genes in the uterus and vagina identified by profiling provide an important foundation understanding functional mechanisms of estrogen regulating morphogenesis and maintenance of each reproductive organ.

Placental passage of anesthetics and adjuvants

In obstetric anaesthesia almost all anaesthetic agents are capable of traversing the fetomaternal blood barrier. They all carry potential side-effects putting the unborn or newborn child at risk. Of major relevance is their potential for embryotoxicity, teratogenicity, postpartal cardiorespiratory or neuromuscular depression and the disturbance of thermoregulation. This can possibly lead to fetal malformation, asphyxia or floppy infant syndrome. Furthermore compromisation of uterine blood flow or contractility of the mature uterus plays an important role for the incidence of intrauterine asphyxia and premature labour or birth. Considering the physiological and pathophysiological alterations during pregnancy regarding all organ systems, the overall goal is to find an ideal choice of anaesthetic drugs and techniques in order to minimise an increased anaesthetic risk during pregnancy.

Poor uterine development in Turner syndrome with oral oestrogen therapy.

To evaluate uterine development in Turner syndrome (TS) patients in relation to treatment with oral ethinyl oestradiol (E2 ) for pubertal induction. Pelvic ultrasound data for 96 TS patients scanned since 1989 were analysed. Patients were classified into three groups: (1) untreated (n = 48); (2) complete spontaneous puberty (n = 10); and (3) treated with ethinyl oestradiol (n = 38). Uterine development was described in the three groups and compared with the normal data. Uterine length, fundal-cervical ratio (FCR) and shape were recorded, and presence or absence of ovaries noted. In the treated group, cross-sectional and longitudinal data were combined to compare uterine development with Tanner breast stage. In untreated girls up to age 10 years there was a variable distribution of uterine length and FCR about the mean. Thereafter, the uterus failed to grow and mature normally. Girls with complete spontaneous puberty had morphologically normal ovaries and uteri, but of 7 girls who attained menarche, 3 subsequently developed secondary oligomenorrhoea or amenorrhoea. In the treated group, in general, breast development and uterine length progressed with increasing E2 dose. However, only 50% of girls with complete secondary sexual development had a mature heart-shaped uterine configuration. Our current E2 treatment regimen for TS girls gives rise to satisfactory pubertal induction and maintenance, but failed to induce a fully mature uterus in half the cohort. In view of the high risk of miscarriage in TS in both spontaneous and assisted pregnancies, the effect of more physiological methods of E2 replacement on uterine development should be investigated.

Eotaxin Is Required for Eosinophil Homing into the Stroma of the Pubertal and Cycling Uterus

The presence of eosinophils in the endometrium of rodents during the estrous cycle or after E2 administration to ovariectomized animals is well documented. Nevertheless, the chemoattractant for eosinophils and the function of E-dependent eosinophils during the estrous cycle remain unknown. Using mice homozygous for a null mutation in the gene for eotaxin, a specific chemokine for eosinophils, we have identified eotaxin as being necessary for eosinophil homing into the uterine stroma, and regulated by E2 during the estrous cycle. In the absence of eosinophils, the onset of estrous cycle displayed a 2-wk delay along with the first age of parturition, suggesting a possible local role of eosinophils present in the pubertal uterus in preparing the mature uterus for pregnancy. However, despite the absence of eosinophils, once the mice reach maturity, their estrous cycles as well as their reproductive functions were normal. Our results demonstrate that E2 acts through eotaxin to recruit eosinophils to the uterine stroma during the estrous cycle in mice, but that these cells do not have a function in regulating either the duration of the estrous cycle or fertility of mice.

Eotaxin is required for eosinophil homing into the stroma of the pubertal and cycling uterus.

The presence of eosinophils in the endometrium of rodents during the estrous cycle or after E2 administration to ovariectomized animals is well documented. Nevertheless, the chemoattractant for eosinophils and the function of E-dependent eosinophils during the estrous cycle remain unknown. Using mice homozygous for a null mutation in the gene for eotaxin, a specific chemokine for eosinophils, we have identified eotaxin as being necessary for eosinophil homing into the uterine stroma, and regulated by E2 during the estrous cycle. In the absence of eosinophils, the onset of estrous cycle displayed a 2-wk delay along with the first age of parturition, suggesting a possible local role of eosinophils present in the pubertal uterus in preparing the mature uterus for pregnancy. However, despite the absence of eosinophils, once the mice reach maturity, their estrous cycles as well as their reproductive functions were normal. Our results demonstrate that E2 acts through eotaxin to recruit eosinophils to the uterine stroma during the estrous cycle in mice, but that these cells do not have a function in regulating either the duration of the estrous cycle or fertility of mice.

Demonstration, localization, and development of galanin receptors in the quail oviduct

We recently isolated an oviposition-inducing peptide that was identified as avian galanin from the oviducts of the Japanese quail. Avian galanin was localized in neural fibers distributed in muscle layers in the uterine and vaginal oviduct regions, and potentiated spontaneous contractions of the uterus and vagina. To elucidate whether an oviposition-inducing effect of avian galanin is due to the direct action on the oviduct, therefore, a specific binding site for avian galanin was determined in the functional quail oviduct in this study. The binding of [125I]iodoavian galanin was primarily located in the oviduct as well as the brain. The galanin binding was specifically inhibited as a function of the concentrations of both avian and rat galanins. The specific binding of avian galanin to the quail oviduct was temperature dependent and reached the maximum level for 1 h at 20 degrees C. In several regions of the oviduct, a higher level of specific galanin binding was observed only in the uterus and vagina. In contrast, the specific binding was low in the isthmus and negligible in the magnum. A similar localization was evident in the functional chicken oviduct. The Scatchard plot analysis of the binding of avian galanin to the uterine preparation revealed that the dissociation constant (Kd) was 0.249 (95% confidence interval, 0.192-0.356) nM, and the number of binding sites was 1.13 (0.99-1.36) fmol per mg tissue, respectively. During development, the galanin-binding sites were apparent in the quail oviduct at 3 weeks of age and the number of binding sites markedly increased between 3 weeks and 3 months of age. However, there was no significant change in the Kd value in the developing quail oviduct. This is the first demonstration of the presence of galanin receptors in the reproductive tract, such as the uterine and vaginal oviduct. The present results suggest that the number of galanin receptors in the oviduct increases during development and that galanin acts directly on the mature uterus and vagina to induce their contractions. This mechanism may be essential to the avian oviposition.

Demonstration, localization, and development of galanin receptors in the quail oviduct

We recently isolated an oviposition-inducing peptide that was identified as avian galanin from the oviducts of the Japanese quail. Avian galanin was localized in neural fibers distributed in muscle layers in the uterine and vaginal oviduct regions, and potentiated spontaneous contractions of the uterus and vagina. To elucidate whether an oviposition-inducing effect of avian galanin is due to the direct action on the oviduct, therefore, a specific binding site for avian galanin was determined in the functional quail oviduct in this study. The binding of [125I]iodoavian galanin was primarily located in the oviduct as well as the brain. The galanin binding was specifically inhibited as a function of the concentrations of both avian and rat galanins. The specific binding of avian galanin to the quail oviduct was temperature dependent and reached the maximum level for 1 h at 20°C. In several regions of the oviduct, a higher level of specific galanin binding was observed only in the uterus and vagina. In contrast, the specific binding was low in the isthmus and negligible in the magnum. A similar localization was evident in the functional chicken oviduct. The Scatchard plot analysis of the binding of avian galanin to the uterine preparation revealed that the dissociation constant (Kd) was 0.249 (95% confidence interval, 0.192–0.356) nM, and the number of binding sites was 1.13 (0.99–1.36) fmol per mg tissue, respectively. During development, the galanin-binding sites were apparent in the quail oviduct at 3 weeks of age and the number of binding sites markedly increased between 3 weeks and 3 months of age. However, there was no significant change in the Kd value in the developing quail oviduct. This is the first demonstration of the presence of galanin receptors in the reproductive tract, such as the uterine and vaginal oviduct. The present results suggest that the number of galanin receptors in the oviduct increases during development and that galanin acts directly on the mature uterus and vagina to induce their contractions. This mechanism may be essential to the avian oviposition. J. Exp. Zool. 277:57–65, 1997. © 1997 Wiley-Liss, Inc.

Differential effect of estrogen on the production of cyclin B1, cdc2 p34 and c-fos protein in rat uterus.

The uterine content of c-fos protein, cyclin B1 (cell cycle protein) and cdc2 p34(cyclin-dependent kinase) in immature and mature rats was determined using the enhanced chemiluminescence(ECL) western blot method. Cyclin B1 was found predominantly in immature rat uterus and cdc2 p34 only in mature rat uterus. Several isoforms of c-fos oncogene protein were present in both mature and immature rat uteri. An additional immunoreactive c-fos protein with an estimated molecular weight of 28 kDa was found in mature rat uterus and was missing in immature uterus. Uteri from ovariectomized rats treated with estrogen and/or ICI 182,780, an antiestrogen, were analyzed by ECL western blot. cdc2 p34 and the c-fos 28 kDa protein were found in estradiol-treated rat uteri and were not detected in uteri of control and ICI 182,780-treated animals; whereas Cyclin B1 was absent in uteri from control and estradiol-treated ovariectomized animals. ICI 182,780 administered to estradiol-treated ovariectomized rats blocked the induction of cdc2 p34 and the c-fos 28 kDa protein in the uterus. The present results show that the production of the cell cycle factors, cyclin B1, cdc2 p34 and c-fos, during rat uterine growth are under different regulatory controls. cdc2 p34 and c-fos 28 kDa protein are under the control of estradiol; whereas cyclin B1 and the majority of the immunoreactive isoforms of c-fos are not influenced by this hormone.

Estrogen differentially affects c-jun expression in uterine tissue compartments.

Estrogen rapidly induces expression of the jun immediate early gene family in mature and immature rodent uteri, suggesting that these protooncogenes are directly involved in the proliferative response of the uterus to estrogen. The jun family mRNAs, however, have not been localized to specific uterine cell types. Furthermore, it is necessary to differentiate between the response of the immature vs. the mature rat uterus to 17 beta-estradiol (E2-17 beta), because in the former, all uterine cell types respond to estrogen with increased DNA synthesis, but in the latter, the proliferative response is restricted to the uterine epithelial cells. In the present study, in situ hybridization was used to determine the cell type-specific location of mRNA encoding the immediate early genes c-jun, jun-B, and jun-D after the administration of E2-17 beta to mature and immature rats. Estradiol stimulated jun-B and jun-D expression primarily in the uterine luminal and glandular epithelium. The pattern of c-jun expression, however, was strikingly different; E2-17 beta repressed c-jun mRNA levels in the uterine luminal epithelium and simultaneously increased c-jun expression in the uterine myometrium. In mature vs. immature uteri, the general cell type-specific patterns of jun-B and jun-D expression were similar after estrogen administration. The expression of c-jun was increased by estrogen in the uterine glands as well the uterine myometrium of immature rats; however, in mature rats, uterine glandular epithelial cells did not respond to E2-17 beta administration with increased c-jun expression. These experiments demonstrate for the first time positive and negative regulatory actions of estrogen on c-jun expression and suggest a role for tissue-specific factors in the control of c-jun expression. The lack of maturational effects on jun gene expression implies that the differential response of the immature vs. the mature uterus to estrogen, in terms of cell proliferation, involves a point of control other than that at the level of the jun protooncogene family.