Ovarian Steroid Receptors Research Articles

A protocol for creating endometriosis in rhesus macaques (Macaca mulatta).

Endometriosis is the presence of endometrium-like tissue outside the uterine cavity. An experimental model of endometriosis has been created in the baboon by the transcervical collection and laparoscopic inoculation of menstrual endometrium. Macaques are the preferred model for pharmaceutical development, but the complex anatomy of the macaque cervix makes the baboon method impractical. In this work, we sought to validate a surgical approach for creating endometriosis in macaques. Menstrual endometrium was collected via laparoscopic intrauterine puncture and transferred to the peritoneal cavity. We repeated this procedure during three menstruations. Endometriotic tissue was identified during laparoscopy, collected, and characterized by immunohistochemistry. Sham surgery-treated animals (n = 3) failed to develop endometriosis. We identified red, powder burnt, and white lesions in 13/14 of the treated animals; the stroma of the red lesions stained positive for ovarian steroid receptors. This surgical technique can reliably create hormone-responsive endometriosis in macaques for therapeutic studies.

Is neonatal uterine bleeding responsible for early-onset endometriosis?

BackgroundIt has been hypothesized that the origin of early-onset endometriosis could be from endometrial mesenchymal stem cells (eMSCs) in neonatal uterine blood (NUB). There is no information on the possible mechanistic basis linking an association between NUB/neonatal endometrium and development of early-onset endometriosis. In this study we performed a series of experiments to clarify the mechanistic link between NUB and/or neonatal endometrium and development of early-onset endometriosis.MethodsWe retrospectively collected postmortem neonatal endometria (n = 15) and prospectively collected NUB (n = 18) of female babies for the analysis of different biological markers including eMSCs. Immunohistochemical analysis of neonatal endometria was performed to examine the expression patterns of ovarian steroid receptors (ER/PGR), decidualization (prolactin, IGFBP1), pre-decidualization (Glycodelin A, α-SMA), proliferation (Ki-67 index), vascularity (CD31 + cells), immunocompetent CD68+, CD45+, CD56 + cells and some putative markers of eMSCs. Cell transfer method and immunocytochemistry were used to investigate the eMSCs and/or endometrial cells in NUB.ResultsImmunohistochemical analysis of postmortem neonatal endometria revealed variable staining response to ER/PGR, decidual markers, and substantial proliferative and angiogenic activity. A moderate to strong immunoexpression of Glycodelin-A was found in both neonatal and adult endometria. The tissue infiltration of CD56+, CD45 + and CD68 + immunocompetent cells was significantly low in neonatal endometria than that in adult endometria (p = 0.0003, p < 0.0001, p = 0.034, respectively). No eMSCs or even endometrial cells were detected in NUB. However, a variable expression of some phenotypes of eMSCs (CD90/CD105) was found in neonatal endometria.ConclusionsBased on our serial experiments we did not find any supporting evidence for the role of NUB in early-onset endometriosis. Neonatal endometria showed variable expression of ovarian steroid receptors, decidualization, and a substantial amount of proliferative and angiogenic activity. As an alternative mechanism, a significantly less tissue accumulation of immunocompetent cells in neonatal endometria may explain the survival of ER + and PGR + cells should they make entry into the pelvis and consequent development of early endometriosis with the onset of ovarian function. Future study with large sample size and application of modified technological tools is warranted to test the NUB hypothesis and to clarify their biological or clinical significance.Trial registrationnot applicable.

The Notch Family Transcription Factor, RBPJκ, Modulates Glucose Transporter and Ovarian Steroid Hormone Receptor Expression During Decidualization.

During decidualization, endometrial stromal cells differentiate into a secretory phenotype to modulate the uterine microenvironment and promote embryo implantation. This highly metabolic process relies on ovarian steroid receptors and glucose transporters. Canonical Notch signaling is mediated by the transcription factor Recombination Signal Binding Protein for Immunoglobulin Kappa J Region (RBPJ). Loss of RBPJ in the mouse uterus (Pgrcre/+Rbpjflox/flox; Rbpj c-KO) results in subfertility in part due to an abnormal uterine-embryonic axis during implantation and, as described herein, decidualization failure. Induced in vivo decidualization in Rbpj c-KO mice was impaired with the downregulation of decidual markers and decreased progesterone receptor (Pgr) signaling. Consistent with in vivo mouse data, RBPJ knockdown during in vitro Human uterine fibroblast (HuF) cell decidualization results in the reduced expression of decidual marker genes along with PGR. Expression of the glucose transporter, SLC2A1, was decreased in the RBPJ-silenced HuF cells, which corresponded to decreased Slc2a1 in the secondary decidual zone of Rbpj c-KO mouse uteri. Exogenous administration of pyruvate, which bypasses the need for glucose, rescues PRL expression in RBPJ-deficient HuF cells. In summary, Notch signaling through RBPJ controls both ovarian steroid receptor PGR and glucose transporter SLC2A1 expression during decidualization, and this dysregulation likely contributes to embryo implantation failure.

Endocrine therapy in ovarian cancer: where do we stand?

Hormonal factors play a pivotal role in epithelial ovarian tumorigenesis and steroid receptor expression has been associated with epithelial ovarian cancer (EOC) response and survival in recent studies. However, the degree of activity of endocrine therapy overall and by specific agents remains unclear. The purpose of this work is to summarize the evidence provided by the recent literature on the effectiveness of endocrine treatment for advanced EOC. The results of 53 trials of different endocrine therapies in EOC indicate a clinical benefit of 41% [95% confidence interval (CI), 0.34-0.48], with a trend for a higher benefit in those with estrogen receptor (ER) + and/or progesteron receptor (PgR) + tumors. Moreover, the odd ratio for death showed a reduced mortality with endocrine regimens (0.69, 95% CI, 0.50-0.97), with a propensity for a better outcome in first-line and low-grade tumors. We suggest that ER and PgR have a predictive role and their inhibition by endocrine therapy may be a treatment option for EOC. Randomized clinical trials in the first-line treatment of advanced hormone receptor positive EOC are warranted given the potential cost effectiveness of this approach.

α-Estrogen and Progesterone Receptors Modulate Kisspeptin Effects on Prolactin: Role in Estradiol-Induced Prolactin Surge in Female Rats.

Kisspeptin (Kp) regulates prolactin (PRL) in an estradiol-dependent manner. We investigated the interaction between ovarian steroid receptors and Kp in the control of PRL secretion. Intracerebroventricular injections of Kp-10 or Kp-234 were performed in ovariectomized (OVX) rats under different hormonal treatments. Kp-10 increased PRL release and decreased 3,4-dihydroxyphenylacetic acid levels in the median eminence (ME) of OVX rats treated with estradiol (OVX+E), which was prevented by tamoxifen. Whereas these effects of Kp-10 were absent in OVX rats, they were replicated in OVX rats treated with selective agonist of estrogen receptor (ER)α, propylpyrazole triol, but not of ERβ, diarylpropionitrile. Furthermore, the Kp-10-induced increase in PRL was two times higher in OVX+E rats also treated with progesterone (OVX+EP), which was associated with a reduced expression of both tyrosine hydroxylase (TH) and Ser40-phosphorylated TH in the ME. Kp-10 also reduced dopamine levels in the ME of OVX+EP rats, an effect blocked by the progesterone receptor (PR) antagonist RU486. We also determined the effect of Kp antagonism with Kp-234 on the estradiol-induced surges of PRL and luteinizing hormone (LH), using tail-tip blood sampling combined with ultrasensitive enzyme-linked immunosorbent assay. Kp-234 impaired the early phase of the PRL surge and prevented the LH surge in OVX+E rats. Thus, we provide evidence that Kp stimulation of PRL release requires ERα and is potentiated by progesterone via PR activation. Moreover, alongside its essential role in the LH surge, Kp seems to play a role in the peak phase of the estradiol-induced PRL surge.

Ovarian sex steroid receptors and sex hormones in androgenized rats

This study evaluated for the first time the effects of different doses of the anabolic steroid nandrolone decanoate (ND) on the expression of ovarian steroid receptors (AR, ER-α (ESR1) and ER-β (ESR2)) and related sex hormones after treatment and recovery periods in adult rats. The animals were injected subcutaneously with doses of ND (1.87, 3.75, 7.5 or 15 mg/kg b.w.) or mineral oil (control group) for 15 days, and the experimental groups were divided into three periods of evaluation: (a) ND treatment for 15 days, (b) ND treatment and recovery for a period of 30 days and (c) ND treatment and recovery for a period of 60 days. Estrous cycle was monitored daily. At the end of each period, rats were killed for collection of blood and ovaries. Persistent diestrus occurred in all rats during ND treatment and after 30-day recovery. The highest dose of ND was able to maintain all rats arrested at diestrus until 60-day recovery. The expression of steroid receptors varied in a dose- and period-dependent manner, having a more pronounced response with the dose of 15 mg ND/kg. ND treatment increased serum levels of testosterone, 17β-estradiol and dihydrotestosterone, especially at the highest doses of 7.5 and 15 mg ND/kg. No change was observed in the levels of follicle-stimulating hormone (FSH), whereas levels of the luteinizing hormone (LH) varied according to the dose and period. In conclusion, the ovarian sex steroid receptors and sex hormones were restored only at lower doses of ND and after a longer period of recovery.

Endocrine therapy for ovarian cancer: A systematic review and meta-analysis of phase II studies.

5554Background: Hormonal factors play a key role in epithelial ovarian tumorigenesis and steroid receptor expression has been associated with epithelial ovarian cancer (EOC) response and survival i...

Inhibition of Insulin like growth factor-I expression by chromatographic fraction of Polygonum hydropiper root reduces implantation preference in rat

Objective of the investigation was to determine if, the phytocompound(s) present in the root of Polygonum hydropiper could inhibit implantation mediating the regulation of Insulin like growth factor (IGF-I) mRNA transcript. A prospective study. Department of Zoology of Rajiv Gandhi University. The root extract of P. hydropiper was fractionated by thin layer chromatography using estradiol-17β (E2) as reference compound. The fraction with a similar R f value as that of E2 was administered subcutaneously to pregnant rats in a dose of 5 mg/kg body weight from day 1 to day 6 of gestation. Implantation sites were counted on day 6 of gestation. Expression of IGF-I in situ was localised in paraffin embedded sections where in, mRNA transcript was studied by RT-PCR in uterine tissues from day 2 to day 6 of gestation. Inhibition of embryo implantation mediating regulation of Insulin like growth factor (IGF-I) mRNA transcript. Pregnant female rats treated with chromatographic fraction showed a decreased number of implantation sites. The inhibition of implantation by the chromatographic fraction of the root extract of P. hydropiper was associated with failure of decidual cell reaction in the primary decidual zone. During this critical period of fetal–maternal interaction the number of IGF-I mRNA transcripts gradually decreased resulting in a decreased expression of the growth factor in uterus. The root of P. hydropiper contains compound(s) with capability to modulate transcription and expression of IGF-I in rat uterus during early gestation. Down regulation of IGF-I results suggests that the phytocompound(s) work through the ovarian steroid receptor(s) resulting in an inhibition of decidual cell reaction and implantation.

Validation of the Aging Hen (Gallus gallus domesticus) as an Animal Model for Uterine Leiomyomas1

Uterine leiomyomas, or fibroids, are the most frequent gynecological tumors in premenopausal women with as many as 65% of women becoming clinically symptomatic. Uterine fibroids are benign myometrial tumors that produce large quantities of extracellular matrix proteins. Despite its high morbidity, the molecular basis underlying the development of uterine leiomyomas is not well understood. Domestic hens of Gallus gallus domesticus develop oviductal leiomyomas similar to those found in humans. We investigated the natural history of chicken leiomyomas, in vivo expression of protein biomarkers, and in vitro expression of ovarian steroid receptors. Based on the analysis of 263 hens, tumor prevalence, tumor number per hen, and tumor size increased as the hens aged. Immunohistochemistry for alpha-smooth muscle actin (SMA) and desmin confirmed the smooth muscle phenotype of the chicken leiomyomas. Intense collagen expression was detected in these oviductal leiomyomas by Mason's trichrome, and the tumors also showed increased expression of TGFB3 and collagen type I mRNAs. Consistent with human leiomyomas, chicken fibroids displayed increased BCL2 and estrogen (E) and progesterone (P) receptor expression. Chicken leiomyomas were dissociated for in vitro culture. Cells from explants were positive for SMA, desmin, and E and P receptors until the fourth passage. These cells also displayed a response similar to human cells when challenged with halofuginone, an antifibrotic agent. Our findings indicate that the chicken is an excellent complementary model for studies involving the pathophysiology of human uterine leiomyomas.

Lipopolysaccharide-induced modulation in the expression of progesterone receptor and estradiol receptor leads to early pregnancy loss in mouse

The objective of the present study was to investigate the effect of Gram-negative bacteria infection on ovarian steroid receptors, i.e. progesterone receptor (PR) and estradiol receptor (ER) during preimplantation days of pregnancy. A well established mouse model of Gram-negative bacteria infection was used to test this objective. Mice were treated with normal saline or lipopolysaccharide (LPS) on day 0.5 of pregnancy and used to collect embryos and uterine horns on day 1.5 to day 4.42 preimplantation day of pregnancy. Total RNA was extracted and reverse-transcription polymerase chain reaction (PCR) was performed to check the expression of PR and ER genes. The mRNA expression of PR and ER was altered in embryos and uterus of LPS-treated animals during preimplantation days of pregnancy studied. These results suggest that PR and ER play an important role in Gram-negative bacteria infection and induced implantation failure in mouse.

Steroid receptor mRNA expression in the ovarian follicles of cows with cystic ovarian disease

Steroid receptors have been demonstrated to be important intra-ovarian regulators of follicular development and ovulatory processes. The aim of the present study was to determine the expression of steroid receptor mRNA in ovarian follicular structures from cows with cystic ovarian disease (COD) compared with ovarian structures from regularly cycling cows using reverse transcription polymerase chain reaction (RT-PCR). The cystic follicles showed a higher estrogen receptor α (ESR1) mRNA expression in the theca and granulosa and a lower estrogen receptor β (ESR2) expression. The cystic follicles also showed a strong expression of androgen receptor mRNA in the granulosa. No changes were observed in total progesterone receptor mRNA, but a very significant increase in the B isoform was found in the granulosa of the cystic follicles. The findings of the current study provide evidence that an altered steroid signaling system may be present in bovine follicular cysts, and we suggest that in conditions characterized by altered ovulation, such as COD, changes in the expression of ovarian steroid receptors could play a fundamental role in the pathogeny of this disease.

Ovarian Steroid Receptors and Activated MAPK in the Regional Decidualization in Rats1

Though the decidua serves a critical function in implantation, the hormonal regulated pathway in decidualization is still elusive. Here we describe in detail the regional distribution and the effects of progesterone receptors (PGR), estrogen receptors (ESR), and MAPK activation on decidualization. We showed an increase in PGR A, PGR B, ESR1, and phosphorylated MAPK3-1 proteins (p-MAPK3-1), but not in ESR2, in the decidual tissue up to Day 8 of pregnancy. PGR was predominantly found in the nuclei of mesometrial decidual cells and of undifferentiated stromal cells where it colocalizes with ESR2 and ESR1. In the antimesometrial decidua, all the receptors showed cytoplasmic localization. MAPK was activated exclusively in undifferentiated stromal cells of the junctional zone between the antimesometrial and mesometrial decidua and at the border of the antimesometrial decidua. Treatment with the progesterone antagonist onapristone and/or the estrogen antagonist faslodex reduced the extent of decidual tissue and downregulated the levels of PGR and ESR1. The expression level of ESR2 was affected only by the progesterone receptor antagonist, while neither the antiprogestin nor the antiestrogen significantly modified the p-MAPK3-1 level. The inhibition of MAPK3-1 phosphorylation by PD98059 impaired the extent of decidualization and the closure reaction of the implantation chamber, and significantly downregulated ESR1. These results confirm a role of both steroid receptors in the growth and differentiation of the different decidual regions and suggest a new function for p-MAPK3-1 in regulating expression levels of ESR1, thereby maintaining the proliferation capacity of stromal cells and limiting the differentiation process in specified regions of decidual tissues.

Developmental programming: prenatal androgen excess disrupts ovarian steroid receptor balance

Steroid hormones play an important role in reproduction and the receptors through which they signal change in a developmental time, follicle stage, and cell-specific manner. Disruption in steroid receptor expression affects follicle formation and differentiation. In this study, using prenatal testosterone (T) and dihydrotestosterone (DHT)-treated female sheep as model systems, we tested the hypothesis that prenatal androgen excess disrupts the developmental ontogeny of ovarian steroid receptor protein expression. Pregnant Suffolk ewes were injected twice weekly with T propionate or DHT propionate (a non-aromatizable androgen) in cottonseed oil from days 30 to 90 of gestation. Changes in ovarian estrogen receptors (ER; ESR1, ESR2), androgen receptor (AR) and progesterone receptor (PGR) proteins were determined at fetal (days 90 and 140), postpubertal (10 months), and adult (21 months; only prenatal T-treated sheep studied) ages by immunohistochemistry. Prenatal T and DHT treatment induced selective increase in AR but not ER or PGR expression in the stroma and granulosa cells of fetal days 90 and 140 ovaries. An increase in ESR1 and decrease in ESR2 immunostaining coupled with increased AR expression were evident in granulosa cells of antral follicles of 10- and 21-month-old prenatal T but not DHT-treated females (analyzed only at 10 months). These findings provide evidence that an early increase in ovarian AR is the first step in the altered ovarian developmental trajectory of prenatal T-treated females, and manifestations of postnatal ovarian dysfunction are likely facilitated via altered equilibrium of antral follicular granulosa cell ER/AR protein expression.

Myometrial oxytocin receptor mRNA concentrations at preterm and term delivery – the influence of external oxytocin

The hormonal system for induction of term and preterm labour is not fully understood. Therefore, we investigated myometrial gene expressions for neurohypophyseal hormones and their receptors, prostaglandin F2α and ovarian steroid receptors in women delivered by Caesarean section. Myometrial tissue for real time PCR was collected from 39 women delivered at term before and after the onset of labour and preterm. Women delivered electively at term had significantly higher oxytocin receptor mRNA expressions (2.52 ± 0.37 oxytocin receptor/actin; median ± SEM) than those delivered with ongoing labour at term (1.01 ± 0.34; p = 0.015) and those at preterm (1.08 ± 0.25; p = 0.004). Sub-analyses revealed that the difference at term pregnancies solely was related to patients receiving oxytocin during labour (p = 0.007). These patients had higher oxytocin peptide mRNA levels than those without labour at term (p = 0.009). PGF2α receptor mRNA concentrations were 27.80 ± 3.55, 11.46 ± 2.87 and 19.54 ± 5.52 PGF receptor/actin, respectively, for the groups. Women without labour at term had higher concentration than those with labour (p = 0.005). Our results suggest that oxytocin, its receptor and the PGF2α receptor are involved in the regulation of labour through a paracrine mechanism.

Hippocampal dynorphin immunoreactivity increases in response to gonadal steroids and is positioned for direct modulation by ovarian steroid receptors

The hippocampal formation (HF) is involved in modulating learning related to drug abuse. While HF-dependent learning is regulated by both endogenous opioids and estrogen, the interaction between these two systems is not well understood. The mossy fiber (MF) pathway formed by dentate gyrus (DG) granule cell axons is involved in some aspects of learning and contains abundant amounts of the endogenous opioid peptide dynorphin (DYN). To examine the influence of ovarian steroids on DYN expression, we used quantitative light microscopic immunocytochemistry to measure DYN levels in normal cycling rats as well as in two established models of hormone-treated ovariectomized (OVX) rats. Rats in estrus had increased levels of DYN-immunoreactivity (ir) in the DG and certain CA3 lamina compared with rats in proestrus or diestrus. OVX rats exposed to estradiol for 24 h showed increased DYN-ir in the DG and CA3, while those with 72 h estradiol exposure showed increases only in the DG. Six hours of estradiol exposure produced no change in DYN-ir. OVX rats chronically implanted with medroxyprogesterone also showed increased DYN-ir in the DG and CA3. Next, dual-labeling electron microscopy (EM) was used to evaluate the subcellular relationships of estrogen receptor (ER) α-, ERβ and progestin receptor (PR) with DYN-labeled MFs. ERβ-ir was in some DYN-labeled MF terminals and smaller terminals, and had a subcellular association with the plasmalemma and small synaptic vesicles. In contrast, ERα-ir was not in DYN-labeled terminals, although some DYN-labeled small terminals synapsed on ERα-labeled dendritic spines. PR labeling was mostly in CA3 axons, some of which were continuous with DYN-labeled terminals. These studies indicate that ovarian hormones can modulate DYN in the MF pathway in a time-dependent manner, and suggest that hormonal effects on the DYN-containing MF pathway may be directly mediated by ERβ and/or PR activation.

Cells in Behaviourally Relevant Brain Regions Coexpress Nuclear Receptor Coactivators and Ovarian Steroid Receptors

Oestradiol and progesterone act in the brain to elicit profound effects on behaviour and physiology. One physiological function of oestradiol is the induction of progesterone receptor (PR) expression in a variety of behaviourally relevant brain regions, including the ventromedial nucleus of the hypothalamus (VMN), the medial preoptic nucleus of the preoptic area (MPOA), the arcuate nucleus (ARC) and the medial central grey (MCG). Ligand-dependent transcriptional activity of steroid receptors, including oestrogen receptors (ER) and Pr, is dramatically influenced by nuclear receptor coactivators. In previous studies, we have found that two of these nuclear receptor coactivators, steroid receptor coactivator-1 (SRC-1) and CREB-binding protein (CBP), are important in ER-mediated induction of PR in the VMN and in steroid-dependent behaviours. For nuclear receptor coactivators to function in hormone-dependent transcription in the brain and regulate behaviour, both receptor and coactivator must be expressed in the same cell. In the present study, we used a dual-label immunohistochemical technique to investigate if individual cells in behaviourally relevant brain regions coexpress nuclear receptor coactivators and steroid receptors. Confocal analysis revealed that in oestrogen-primed rats, most of the E-induced PR cells in the VMN (89.6%), MPOA (63%), ARC (82.6%), and many in the MCG (39%), also express SRC-1. In addition, the majority of the cells containing E-induced PR in the VMN (78.3%), MPOA (83.1%), ARC (83.6%), and MCG (60%) also express CBP. These results, taken together with the findings that virtually all oestradiol-induced PR containing cells in the brain express ER, suggest that these neurones represent sites of functional interaction of nuclear receptor coactivators with ovarian steroid receptors in the brain. The present findings provide neuroanatomical evidence that nuclear receptor coactivators are integral in mediating steroid hormone action in behaviourally relevant brain regions.

The effect of dexamethasone on disruption of ovarian steroid levels and receptors in female rats

This study was conducted to investigate if the injection of a single dose of dexamethasone may cause disruption of adult female rat gonadal function in terms of plasma and ovarian level of both androgen and estrogen, ovarian morphology, and changes in localization of androgen, estrogen and glucocorticoid receptors. Adult female Long Evans rats (n=50, 250-300 g) were used. At day 0 rats received subcutaneously 1 ml of saline (n=25; control group) or dexamethasone at 0.1 mg/kg (n=25, treated group). Rats were sacrificed in groups of five on days 10, 15, 20, 25 and 30 after injection. Blood samples and one ovary were collected to analyze dexamethasone, 17beta-estradiol (E2), testosterone (T) and androstenedione (A4) concentrations by amplified EIA. The remaining ovary was removed and processed for histopathology and immunocytochemistry. Differences between individual means were analyzed by Pairwise t-test and Bonferroni post test to asses whether values presented statistical significance. Increased E2, T and A4 levels were observed both in plasma and ovary samples in treated group when comparing with control (p< 0.01) at all days post-injection even when dexamethasone was undetectable. Ovarian morphology of treated group showed features compatible with female infertility. Inmmunolocalization of androgen and estrogen receptors showed that both were negative in treated group while controls showed highest positivity (AR +++, ER ++). Glucocorticoid receptor showed higher positivity in dexamethasone treated rats (GR ++) than in controls (GR +). Obtained results showed clear evidence that a single dose of dexamethasone may disrupt gonadal function in rats, and that possibly leads to infertility.

Diagnostic implications of immunohistochemical markers in uterine smooth muscle tumors

Objective: To evaluate the diagnostic implications of immunohistochemical markers in uterine smooth muscle tumors. Methods: Formalin-fixed paraffin-embedded tissue blocks were selected from 17 uterine leiomyosarcomas, 40 uterine unusual leiomyomas and 25 uterine usual leiomyomas. Utilizing immunohistochemical techniques with antigen retrieval, serial sections of each tumor for immunoreactivity with myogenic markers, ovarian steroid receptors, CD44v3, proliferating cell nuclear antigen and mast cells were assessed. Results: Although the myogenic markers and CD44v3 showed less frequent positivity in uterine leiomyosarcomas than those in unusual leiomyomas, they were not reliable markers for differentiating leiomyosarcoma from leiomyoma. Uterine leiomyosarcoma tended to have lower ovarian steroid receptors immunoreactivity rates than leiomyoma. Leiomyoma tended to have a higher quantity of intratumoral mast cells than leiomyosarcoma, while the expression of proliferating cell nuclear antigen was lower in them. Conclusion: Because the estimation of mitotic count was subject to significant variation, the immunohistochemical expression of ovarian steroid receptors, mast cells and proliferating cell nuclear antigen seemed to be helpful for the discrimination of unusual leiomyoma from leiomyosarcoma.

IL-1α gene expression in human endometrial cancer is independent of ovarian steroid receptor expression

IL-1α gene expression in human endometrial cancer is independent of ovarian steroid receptor expression

Ovarian steroid receptors and their role in ovarian function

The steroidogenic pathway within the ovary gives rise to progestins, androgens and oestrogens, all of which act via specific nuclear receptors to regulate reproductive function and maintain fertility. The precise role of oestrogen in the ovary remains to be elucidated, hence the data presented here which arises from studies designed to resolve this issue. Oestrogens signal via two receptor subtypes ERα and ERβ, both of which are present in the ovary. ERβ, the most abundant mRNA, is primarily expressed by GC where it transduces signals from ovarian-derived and exogenous oestrogens. Specific roles for each of the ERs in the ovary have yet to be established, despite ER knockout studies indicating both are required for normal function. The ArKO mouse is a model of oestrogen insufficiency. These mice are infertile as a result of arrested folliculogenesis (at the antral stage) and a failure to ovulate. Trans/re-differentiation of somatic cells in the ovary gives rise to Sertoli cell-like and Leydig cell-like cells within abnormal follicular structures. Disruption to the balance of sex steroids in the ovary is likely to facilitate this phenotype. Future studies will focus on the regulation of somatic cell differentiation, assigning roles to individual ERs and establishing definitive targets of oestrogen action in the ovary.