Presence Of Steroid Receptors Research Articles

Rare Broad Ligament Cavernous Hemangioma Mimicking Advanced Endometriosis: A Case Report.

Cavernous hemangioma within the female genital tract is an extremely rare pathology, characterized by irregular vascular spaces containing blood or thrombus. We present a unique case of a 42-year-old primiparous woman who presented with typical endometriosis symptoms such as dysmenorrhea, dyspareunia, and heavy menstrual bleeding. The patient also experienced complex postpartum symptoms, which were misdiagnosed as cholecystitis and retained placental products. Imaging studies suggested deep infiltrative endometriosis with extraovarian endometriotic lesions. Surgical exploration revealed a hemangioma within the right anterior broad ligament alongside peritoneal endometriosis lesions. The hemangioma itself expresses estrogen and progesterone receptors in stromal cells. The presence of steroid hormone receptors strongly suggests symptom alleviation during the menstrual cycle and the postpartum period. The coexistence of cavernous hemangioma and endometriosis in the broad ligament, previously unreported, and symptomatic overlap between the two conditions complicates diagnosis and management, emphasizing the need for comprehensive evaluation integrating clinical symptoms and imaging findings.

Vaginal leiomyoma in a goat expressing the nuclear progesterone receptor (PGR): a case report

BackgroundThe risk of developing tumorous diseases in the genital tract also increases with age in animals. One of the classified tumor types is genital leiomyoma. Presently, our understanding of the pathogenesis of this tumor in goats is, however, limited. This accounts also for the information regarding the presence of steroid hormone receptors and, thus, possible responsiveness to circulating steroids.Case presentationThis study describes the case of a vaginal tumor in a seven-year-old Anglo-Nubian goat. The goat was presented due to blood mixed vaginal discharge. Per vaginal examination a singular pedunculated mass in the dorsum of the vagina measuring approximately 3 cm x 4 cm x 4 cm was revealed. After administering epidural anesthesia, the mass was removed electrothermally. There were no postoperative complications. The histopathological examination identified the mass as a leiomyoma. The immunohistochemical examination revealed the presence of the nuclear progesterone receptor (PGR) in the tumor tissue. One year after the surgery, during the follow-up examination, the goat was in good overall health, and the owners had not observed any recurrence of vaginal discharge.ConclusionsWhen observing vaginal discharge in goats, it is important to consider the possibility of genital tract tumors. These tumors may express sex steroid receptors. In the future, it is worth considering the investigation of potential approaches for preventing tumorigenesis or treating the tumor, such as castration or the administration of antiprogestogens.

Sex-based differences in conjunctival goblet cell responses to pro-inflammatory and pro-resolving mediators

Many conjunctival inflammatory diseases differ between the sexes and altered conjunctival goblet cells (CGCs) response is often involved. Inflammation is initiated by the release of pro-inflammatory mediators and terminated by the biosynthesis of specialized pro-resolution mediators (SPMs). Herein, we determined the sex-based difference in the responses of CGCs to inflammatory stimuli or pro-resolving lipid SPMs and their interaction with sex hormones. GCs were cultured from pieces of human conjunctiva in RPMI media. CGCs were transferred 24 h before the start of experiments to phenol red-free and FBS-free media to minimize exogenous hormones. RT-PCR, immunofluorescence microscopy (IF), and Western Blot (WB) were performed to determine the presence of sex hormone receptors. Cellular response to pro-inflammatory stimuli or SPMs was studied by measuring the increase in intracellular [Ca2+] ([Ca2+]i) using fura 2/AM microscopy. Use of RT-PCR demonstrated estrogen receptor (ER) α in 4/5 males and 3/3 females; ERβ in 2/4 males and 2/3 females; and androgen receptors (AR) in 3/3 male and 3/3 female CGCs. Positive immunoreactivity by IF and protein expression by WB was detected using antibodies for the ERα and ERβ in 3/3 males and 3/3 females, while AR were only present in males. Significantly different Ca2+ responses between sexes were found with carbachol only at 10–3 M, but not with histamine or leukotriene (LT) B4 at any concentration used. Incubation with dihydrotestosterone (DHT), estrone (E1), or estradiol (E2) at 10–7 M for 30 min significantly inhibited the LTB4-stimulated [Ca2+]i increase in male and female CGCs. Incubation with DHT, E1, and E2 overnight significantly inhibited the LTB4 response in females, while DHT and E2 significantly inhibited the LTB4 response in males. The SPM lipoxin A4 (LXA4) (10–9–10−8 M), but not the resolvins D1 or D2, induced an [Ca2+]i increase that was significantly higher in males compared to females. We conclude that male and female CGCs showed differences in the expression of sex hormone receptors. Treatment with sex hormones altered pro-inflammatory mediator LTB4-induced response. Males compared to females have a higher response to the ω-6-fatty acid derived SPM LXA4, indicating males may terminate inflammation in conjunctival goblet cells faster than females.

Presence of estrogen and progesterone receptors in proliferating and involuting infantile hemangiomas

Studies in the literature have demonstrated the presence of sex hormone receptors in infantile hemangiomas (IHs), but further investigation is needed to determine the role of these receptors in their proliferation and involution. To date, there are no studies in the literature that aimed to quantitatively examine the expression of sex hormone receptors throughout the different phases of hemangioma development. The objective of our study was to quantitatively evaluate the expression of estrogen (ER) and progesterone (PR) receptors in the proliferative and involuting phases of IHs through the use of real-time polymerase chain reaction (RT-PCR). Twenty IHs (10 proliferating and 10 involuting) were harvested and prepared for molecular investigation. ER receptor alpha (ERα) and beta (ERβ) and the PR expression were examined by RT-PCR and western blot. RT-PCR analysis demonstrated that mRNA expression of ERα, ERβ, and PR was significantly lower in proliferating versus involuting IH. Western blot analysis revealed increased protein expression of ERα in involuting hemangiomas as compared to proliferating ones. Our study demonstrates the variable expression of ER and PR receptors in proliferating and involuting hemangiomas. Further studies are needed to determine the exact role of these hormone receptors in the growth and involution of IHs.

Management strategies and clinical follow-up of pregnant women with intracranial meningioma.

Meningiomas are common primary tumors of the central nervous system. The incidence at the age of fertility is low, although there are some hormonal mechanisms involved. Growth in size was observed during the luteal phase of the menstrual cycle, which could lead to developing new symptoms during pregnancy or worsening of the already existing ones. Visual impairment is the chief complaint, followed by headache, nausea, vomiting, and seizures. Diagnosis is based on neurological examination, ophthalmoscopy, imaging techniques like gadolinium-enhanced magnetic resonance imaging (MRI), and contrast-enhanced computed tomography (CT) scans, bearing in mind the patient’s irradiation and prejudice on the fetus together with the histopathological examination. The objective of the review is to determine the influence of meningioma on pregnancy and vice-versa and provide a strategy of follow-up for maternal-fetal specialists and not only. We performed a systematic review by searching relevant information in PubMed and Wiley databases using keywords as meningioma, pregnancy, progesterone receptors. The results showed that besides a similar incidence of meningioma in pregnant and non-pregnant women, symptoms might flare during pregnancy due to water retention, engorgement of vessels, and the presence of sex hormone receptors on tumor cells. Meningioma may impact the route of pregnancy with adverse effects on the fetus. Thus, fetal monitoring by biophysical profile and cardiotocography (CTG) is needed. The preferred treatment option is surgery, but gestational age and the woman’s status must be taken into consideration.

Expression of metalloproteinases MMP-2 and MMP-9 is associated to the presence of androgen receptor in epithelial ovarian tumors

BackgroundThe current study evaluated the metalloproteinases MMP-2 and MMP-9 expression in epithelial cells and the surrounding stroma in ovarian tumors and the association of MMPs with the histological subtypes, the clinical stage and the presence of steroid hormone receptors. Tumor samples were obtained from 88 patients undergoing surgical cytoreduction of primary ovarian tumors in Instituto Nacional de Cancerología, from México City. The formalin fixed and paraffin embedded samples were processed in order to demonstrate the presence of androgen receptor,estrogen receptor alpha, progesterone receptor, MMP-2,MMP-9 and collagen IV by immunohistochemistry and/or immunofluorescence.ResultsMMP-2 and MMP-9 were differentially expressed in the epithelium and the stroma of ovarian tumors associated to histological subtype, clinical stage and sexual steroid hormone receptor expression. Based on Cox proportional hazard regression model we demonstrated that MMP-2 located in the epithelium and the stroma are independent prognostic biomarkers for overall survival in epithelial ovarian tumors. Kaplan Meir analysis of the combination of AR (+) with MMP-2 (+) in epithelium and AR (+) with MMP-2 (−) in stroma displayed a significant reduction of survival.ConclusionsThe presence of MMP-2 in the stroma of the tumor was a protective factor while the presence of MMP-2 in the epithelium indicated an adverse prognosis. The presence of AR associated with MMP-2 in the tumor cells was a risk factor for overall survival in epithelial ovarian cancer.

SUN-133 Intratumoral Expression of Steroid Receptors, CD68+ Macrophages and Mdm2 in Different Molecular-Biological Types of Endometrial Cancer

Background and aims: In Risk Classifier for Endometrial Cancer/EC (ProMisE) 4 molecular biological types of this tumor are described recently [1,2,3] and need an additional research, including evaluation of hormone-associated characteristics of both tumor tissue and patients [4]. Aim of the work was a study of estrogen (ER) and progesterone (PR) receptors in comparison with CD68+ macrophage infiltration (which promotes the invasion of tumor cells into the myometrium [5]) and expression of MDM2 protein, a negative regulator of p53 [6], in EC types presented in the ProMisE classification. Materials and methods: The tumor tissue of 218 EC patients included in the study (mean age 60.6 years) was assigned according to the data of genetic and immunohistochemical analysis to the types of carcinomas with gene POLE mutations, deficiency of mismatch repair proteins (MMR-D), expression (positive or diffuse) of p53 oncoprotein and to the type without characteristic molecular profile, WCMP. Immunohistochemistry was used also for evaluation of ER (Ventana antibodies, clone SP1) and PR (Ventana antibodies, clone 1E2) according to Allred, MDM2 (antibodies ABCAM, dilution 1:200) and macrophage marker CD68 (DAKO antibodies, clone CD8/144B). Results: According to the averaged data, the highest expression of ER and PR was found in EC types MMR-D and WCMP, and the lowest, respectively, in types POLE and p53+. Most often, positive expression of MDM2 (in 93.2% and 96.9% of studied cases) was detected respectively in MMR-D and p53+ type of EC, indicating, therefore, a positive relationship between MDM2 and the presence of steroid receptors in the first of these types (MMR-D) and negative - in the second of them (p53+). Expression of CD68+ macrophages demonstrated (contrary to the EC types POLE and p53+) a tendency to the lower values in types MMR-D and WCMP (128.0 ± 8.1 and 113.5 ± 6.3 cond.un.), i.e. in tumors with potential sensitivity to estrogen. Conclusions: The results indicate the importance of taking into account of both - the molecular biological type of the EC as well as the role of microenvironment of tumor cells, including the colonization of the neoplasm’ tissue by macrophages (and possibly lymphocytes) and the features of hormonal signal transmission in it. For further analysis, it is desirable to consider also the EC histotype, as one of the factors underlying various prognostic groups of this tumor [7].

Corticotropin Releasing Factor Receptors in breast cancer: Expression and activity in hormone-dependent growth in vitro

Corticotropin Releasing Factor (CRF) neuropeptides coordinate the stress response via two distinct membrane receptors (CRF-Rs). We have previously shown expression of both CRF-Rs in human breast cancer tissues. In the present study, we examined in vitro using the MCF-7 cell line model, the regulation of CRF-Rs expression and their signaling in hormone-dependent breast cancer growth. Our findings show that similarly to breast cancer biopsies, the predominant receptor type expressed in the cell line is CRF-R2α. The transcription of CRF-R1 and CRF-R2 is up and down-regulated respectively by exposure to estradiol (E2); however this effect seems not to be exerted at the level of promoter gene methylation, although in human breast cancer specimens, CRF-R1 methylation was found to be positively associated with the presence of steroid hormone receptors. Finally, we showed that specific activation of CRF-R2 increased the migration of MCF-7 cells and potentiated an estrogen-inducing effect. Our data support an involvement of CRF-R signaling in breast cancer pathophysiology via a regulatory steroid-hormone interplay.

Age and Sex-Related Changes to Gene Expression in the Mouse Spinal Cord.

The spinal cord is essential for neuronal communication between the brain and rest of the body. To gain further insight into the molecular changes underpinning maturation of the mouse spinal cord, we analysed gene expression differences between 4weeks of age (prior to puberty onset) and adulthood (8weeks). We found 800 genes were significantly differentially expressed between juvenile and adult spinal cords. Gene ontology analysis revealed an overrepresentation of genes with roles in myelination and signal transduction among others. The expression of a further 19 genes was sexually dimorphic; these included both autosomal and sex-linked genes. Given the presence of steroid hormone receptors in the spinal cord, we also looked at the impact of two major steroid hormones, oestradiol and dihydrotestosterone (DHT) on spinal cord gene expression for selected genes. In gonadectomised male animals, implants with oestradiol and DHT produced significant changes to spinal cord gene expression. This study provides an overview of the global gene expression changes that occur as the spinal cord matures, over a key period of maturation. This confirms that both age and sex are important considerations in studies involving the spinal cord.

X Chromatin inactivation in Menopause: A study on Hindu caste Bengalee population

Background: Menopause being a physiologic event and eventually the prime time to perform risk assessment of chronic diseases and initiate preventive health measures. Previous studies reported, later menopause is independently associated to increased risk of breast and endometrial cancer. The menopausal status is determined and influenced by intrinsic factors. Majority of the studies on menopause from Indian context, especially on Bengalee Hindu Caste population confined to socio demographic issues, attitudes, problems and quality of life. However, relatively little work is attempted to unravel the complex interplay of genetics and epigenetic mechanisms, the effect on menopause. In this background it seems to be an urgent need to understand menopause status objectively, to approach the interplay of genetics and epigenetic mechanisms of menopausal status by X chromatin inactivation.Aims and Objective: Best of the knowledge it is the first attempt to evaluate the prevalence of X chromatin inactivation in menopausal women among Bengalee Hindu Caste population.Materials and Methods: Sex chromatin inactivation was evaluated from 100 each pre and post menopausal women from the buccal smear of each individuals. After fixation and staining of altogether 20000 (twenty thousand) cells were scanned from the Bengalee Hindu Caste for a comparison of menopausal women and their menarcheal counterparts.Results: Result demonstrated significantly decreased (P<0.001) prevalence of X chromatin inactivation sites among the menopausal females in comparison to their menarcheal women counterpart.Conclusion: The present study vindicated possible association between the presence of sex hormone receptors and the prevalence of sex chromatin and also envisaged the role of X chromatin inactivation for early prognosis of menopause.Asian Journal of Medical Sciences Vol.9(3) 2018 41-45

A Study on Prevalence of Sex Chromatin during Different Reproductive Stage of Bengalee Hindu Caste Females

Human X chromosome has a unique biology that was shaped by its evolution as the sex chromosome shared by males and females. The differential behaviour of the two X chromosome of female cells has biological implications. During the long evolutionary process of humankind, the X chromosome has generated and recruited a disproportionately high number of functional retro-posed genes where as the autosomes experienced tower gene turnover. Recent enquiries have revealed a surprisingly large number of naturally occurring anti-sense transcripts, but their functions remain largely undiscovered. A well documented case occurs in X inactivation, the mechanism by which X-linked gene expression is equalized between XX females and XY males. The anti-sense gene determines X chromosome choice and represses the non-coding silencer. This process of chromosome inactivation (XCI) is a remarkable example of long range, mono-allelic gene silencing and facultative heterochromatin formation. The X chromosome inactivation is initiated from X inactivation centre (XIC), usually found near the centromere. The inactivated X chromosome usually lies along the edge of the interphase nucleus in tightly condensed states. An effect of hormonal factors on the frequency of sex chromatin has been a subject matter of importance since long. The present study was conducted to evaluate the prevalence of sex chromatin and its spatial organization within the nucleus among Bengalee Hindu caste females of different age groups. Buccal smear samples were collected from 150 females belonging to five different reproductive stages of their life- pre-menarchial, post menarchal, pregnant, lactating and menopausal 30 samples were chosen from each of these groups. The remits indicated differential prevalence of sex chromatin among the participants at different reproductive stages. The present study demonstrated that the prevalence of sex chromatin was significantly lowest p<0.001) and highest (p<0.001) among the pre-menarchial females and lactating mothers respectively. On the other hand, the menopausal women revealed significantly lower prevalence (p<0.001) of sex chromatin compared to the participants of rest of the reproductive categories. Furthermore, the present study revealed that the spatial organization differ significantly among different reproductive stages. These results suggested possible association between the presence of steroid hormone receptors and the prevalence of sex chromatin.

Unliganded progesterone receptors attenuate taxane-induced breast cancer cell death by modulating the spindle assembly checkpoint

Whether the presence of steroid receptors in luminal breast cancers renders them resistant to taxanes remains uncertain. Here we assess the role of progesterone receptors (PR) on taxane-induced cell death. We previously showed that estrogen receptor (ER)-positive human breast cancer cells that inducibly express PR-A or PR-B isoforms were protected from taxane-stimulated apoptosis when compared to the identical cells lacking PR. Surprisingly, PR-dependent protection occurred in the absence of progesterone, demonstrating that the unliganded receptors were biologically active. The present studies demonstrate that unliganded PR, focused on PR-A, protect breast cancer cells from taxane-stimulated apoptosis. The studies identify genes regulated by taxanes in isogenic ER-positive cells that either lack or express PR-A. We show that unliganded PR-A alters the gene expression pattern controlled by taxanes, especially multiple genes involved in the spindle assembly checkpoint, a group of proteins that insure proper attachment of microtubules to kinetochores during mitosis. Importantly, taxanes and unliganded PR regulate many of these genes in opposite directions. As a result, mitotic slippage is exacerbated by the presence of PR, leading to an increase in the number of multinucleated cells both in vitro and in xenograft tumors. We describe a simple new assay for assessing multinucleation in paraffin sections. We speculate that rather than inducing cell death, unliganded PR exploits multinucleation to promote cell survival from taxane therapy. This can be prevented with antiprogestin.

Quantification of Steroid Receptors Gene Expression in Breast Cancer Patients: Possible Correlation with Serum Level of Adipocytokines

Background: While the role of adipocyte-derived hormones in breast cancer pathogenesis well studied, it is speculated that there is a crosstalk between adipocytokines and Esterogen receptor(ER) signaling. To test this hypothesis we evaluate the possible correlation between serum levels of adipocytokins with steroid hormone receptors gene expression in breast cancer patients. Methods: In this case-control study, 70 women with breast cancer participated with different grades of obesity (36 none obese, BMI 0.05). In case of leptin, we observed a positive correlation between leptin and ERα and PR mRNA. (r = 0.553, n = 64, p < 0.001, r = 0.359, n = 64, p = 0.002 and a reverse significant correlation between leptin and ERβ (r= –0.506, n = 64 and p < 0.001). We also observed a significant correlation between TNFα and IL6 with steroid receptors gene expression in samples (P < 0.05). Conclusion: As the presence of steroid receptors are used as the most common prognostic markers in breast cancer patients, so targeting adipocytokines as potential regulators of steroid receptorsgene expression can be a new approach in treatment of obese breast cancer subjects.

Steroid receptor expression in the fish inner earvaries with sex, social status, and reproductive state

BackgroundGonadal and stress-related steroid hormones are known to influence auditory function across vertebrates but the cellular and molecular mechanisms responsible for steroid-mediated auditory plasticity at the level of the inner ear remain unknown. The presence of steroid receptors in the ear suggests a direct pathway for hormones to act on the peripheral auditory system, but little is known about which receptors are expressed in the ear or whether their expression levels change with internal physiological state or external social cues. We used qRT-PCR to measure mRNA expression levels of multiple steroid receptor subtypes (estrogen receptors: ERα, ERβa, ERβb; androgen receptors: ARα, ARβ; corticosteroid receptors: GR2, GR1a/b, MR) and aromatase in the main hearing organ of the inner ear (saccule) in the highly social African cichlid fish Astatotilapia burtoni, and tested whether these receptor levels were correlated with circulating steroid concentrations.ResultsWe show that multiple steroid receptor subtypes are expressed within the main hearing organ of a single vertebrate species, and that expression levels differ between the sexes. We also show that steroid receptor subtype-specific changes in mRNA expression are associated with reproductive phase in females and social status in males. Sex-steroid receptor mRNA levels were negatively correlated with circulating estradiol and androgens in both males and females, suggesting possible ligand down-regulation of receptors in the inner ear. In contrast, saccular changes in corticosteroid receptor mRNA levels were not related to serum cortisol levels. Circulating steroid levels and receptor subtype mRNA levels were not as tightly correlated in males as compared to females, suggesting different regulatory mechanisms between sexes.ConclusionsThis is the most comprehensive study of sex-, social-, and reproductive-related steroid receptor mRNA expression in the peripheral auditory system of any single vertebrate. Our data suggest that changes in steroid receptor mRNA expression in the inner ear could be a regulatory mechanism for physiological state-dependent auditory plasticity across vertebrates.

The Histological Origin of Solid-Pseudopapillary Neoplasm of the Pancreas

Solid-pseudopapillary neoplasm of the pancreas (SPNP), as a distinct tumor, often occurred in young female patients with both exocrine and endocrine differentiation. Our aim was to define the SPNP histogenesis and investigate the relationships between its histological origin and the sexual hormone receptors. 20 tumor samples were subjected to the analysis of immunohistologic staining patterns and presence of sex hormone receptors and other markers of SPNP. Immunohistological results indicated that the tumors were positive for alpha-1-antitrypsin (17 cases), vimentin (14 cases), synaptophysin (10 cases), chromaffin granule A (5 cases), cytokeratin and insulin (2 cases), glucagon and S-100 (1 case), progesterone-receptor protein (14 cases), estrogen receptor protein (1 case), pS2 (6 cases), but negative for carcino- embryonic antigen, gastrin and androgen-receptor protein. SPNP is closely associated with the sex hormone receptor.

Immunohistochemical Examinations of Sex Hormone Receptors in Benign Vocal Fold Lesions

Background: Acquired benign vocal fold lesions are among the most common causes of voice problems. Since the local impact of estrogen and progesterone receptors in laryngeal tissue is discussed controversially, the presence of sex hormone receptors in benign vocal fold alterations needs to be clarified. Goal of the Study: To investigate the expression of estrogen-α receptors (ER-α), estrogen-β receptors (ER-β), progesterone receptors (PR) and androgen receptors (AR) in acquired benign vocal fold alterations. Methods: Laryngeal epithelial specimens of 14 patients (13 female, 1 male) taken intraoperatively were investigated using immunohistochemistry in order to objectify ER-α, ER-β, PR and AR. Macroscopically and histopathologically diagnosed edemas of Reinke’s space (n = 10), vocal fold polyps (n = 3) and vocal fold nodules (n = 1) were enrolled in this study. Results: No specific nuclear immunohistochemical staining could be seen in the biopsies taken. Only unspecific staining patterns could be observed. Conclusion: Sex hormone receptors could not be detected in the specimens tested, thus, any direct influence of sex hormones on the development of benign vocal fold lesions is rather unlikely. The results of this study confirm the impact of vocal fold stress and biomechanical abnormalities on their development due to voice overstraining and abuse.

Detection of hormone receptors in the human vocal fold

Until now only limited and controversial data are available concerning the presence of steroid hormone receptors in the human vocal fold. A sum of 140 slides from 104 patients were investigated including 25 Reinke's edemas, 19 cases of recurrent respiratory papillomatosis, 19 polyps, 10 epithelial hyperplasias without or with dysplasias, 4 carcinomas in situ, 20 laryngeal carcinomas as well as 7 fresh cadaver samples without macroscopic alterations. The median patient age was 58 years. Paraffin-embedded tissue was incubated with monoclonal antibodies for estrogen-alpha, androgen and progesterone. Androgen receptors were expressed most frequently, followed by estrogen receptors, whereas no progesterone receptors were identified. Receptor staining could be detected with different densities and locations within the different vocal fold pathologies, but not in the autopsy samples. Our study could clearly demonstrate the presence of hormone receptors in the human vocal fold. Androgen receptors were most frequently detected, especially in the basal and intermediate layer of the stratified epithelium and the lamina propria. Whether the high incidence of steroid hormone receptors in some vocal fold pathologies has implications on their pathogenesis must be evaluated by further studies.

Expression of Ovarian Steroid Hormone Receptors in Tuberoinfundibular Dopaminergic Neurones During Pregnancy and Lactation

During late-pregnancy, tuberoinfundibular dopaminergic (TIDA) neurones, a critical component of the negative-feedback loop regulating prolactin secretion, become unresponsive to the stimulatory effects of prolactin. The change in TIDA responsiveness to prolactin at this time results in a decrease in dopamine secretion and a prolactin surge. As the onset of parturition and the antepartum prolactin surge depend on the withdrawal of progesterone in the presence of oestrogen, it is likely that ovarian steroid hormones mediate this change in TIDA responsiveness. To determine whether ovarian steroids can directly modulate TIDA activity, and whether changes of receptor numbers might contribute to overall steroid-regulation of these neurones, we investigated the level of oestrogen receptor alpha (ERalpha) and progesterone receptor (PR) expression within TIDA neurones during pregnancy and lactation. Animals were sacrificed on dioestrous, days 12, 19 and 21 of pregnancy and day 5 of lactation, and the proportion of TIDA neurones expressing ERalpha or PR, as well as the total number of PR expressing cells within the arcuate nucleus, was determined. Approximately 75% and 55% of tyrosine hydroxylase neurones expressed ERalpha and PR, respectively. Levels of steroid receptor expression within TIDA neurones remained fairly constant, except for an increase in ERalpha on days 12 and 19 of pregnancy compared to dioestrous and lactation day 5. The presence of steroid receptors on TIDA neurones during pregnancy and lactation supports the concept of a direct effect of steroid hormones on these neurones at this time. Thus, steroid hormones may directly act on TIDA neurones to regulate maternal prolactin secretion. The relatively stable level of expression during late pregnancy suggests that a shift in steroid receptor expression during late pregnancy does not contribute to the change in TIDA responsiveness to prolactin at this time.

Cell-specific enhancement of liposomal transfection by steroids in steroid receptor expressing cells

The DNA transfer efficiency in liposomal versus viral transfection is very low, mainly due to an insufficient nuclear transport of the delivered DNA after its endocytotic uptake to the cell. Ligand activation of intracellular steroid receptors and their subsequent mobilization to the nucleus could result in a co-transport of DNA to the nucleus. The augmentation of nuclear transport of DNA after steroid addition might cause enhanced transfection efficiency. We used cell lines from gynecologic malignoma expressing steroid receptors, such as T47D and Mcf-7 breast cancer cell lines, as well as receptor-negative cell lines, such as Hec1A from endometrium carcinoma or the breast cancer cell line MDA-MB-231. The cells were transfected by the liposomal transfection agent Dotap with the gene for firefly-luciferase as a reporter gene and transfection efficiencies were determined in the luciferase assay. We compared the effect of the addition of cholesterol and steroids in different cell lines on the transfection efficiency. The addition of cholesterol to transfection agents led to an enhancement of the luciferase activity in all cell lines. Steroids enhanced the transfection efficiency only in receptor-positive cell lines. The transfection efficiencies of HEC-1A or MDA-MB-231 cells were not enhanced by steroids. A progesterone preincubation of receptor-positive T47D cells resulted in a decrease of progesterone receptors and afterwards the progesterone enhanced transfection was dramatically diminished. We presume that the transfection enhancement by steroids is dependent on increased nuclear import of the delivered DNA only in the presence of steroid receptors. Steroid enhancement of transfection is different from the benefit of cholesterol for transfection that acts on general cellular properties or the transfection complex as such. Liposomal transfection in combination with steroids might be useful for a cell-specific enhancement of gene transfer for example in gynecological malignoma where subgroups are expressing high levels of steroid receptors.

Detection of Steroid Hormone Receptors in the Canine Circumanal Gland

The morphology and function of the circumanal glands in dogs is under current discussion. They are clinically important because they rank fourth in frequency as the site of canine skin tumours. The tissue is known to be governed by steroid hormones, as the gland exhibit sexual dimorphism, castration reduces the size of the gland and lead to tumour regression. The aim of our study was to demonstrate the hormone receptors in healthy circumanal glands as well as adenomas and adenocarcinomas in intact and castrated female and male dogs of different age groups. Immunohistochemical staining was performed using antibodies against androgen receptor (AR, Affinity Bioreagents, rabbit pc, 1:150) and oestrogen receptor (ER, Zymed Lab., rabbit pc, 1:200) after antigen retrieval with microwave cooking. Positive and negative nuclei were counted using Eclipse software and subsequently statistically evaluated. ER and AR‐positive nuclei could be detected in healthy as well as in diseased tissue sections of the circumanal gland. The number of positive nuclei was higher in the flattened peripheral cells compared to the large polygonal cells in the centre of the lobule. There was no significant difference between male and female tissue and between healthy glands and tumours although in tumours there was a tendency to a higher number of positive cells. In tumours, the distribution of hormone receptor positive cells was more irregular and varied between single lobules. Castrated animals of both sexes showed a slightly higher number of positive nuclei than intact animals, but the difference was not significant. Our results demonstrate for the first time the presence of steroid hormone receptors in the canine circumanal gland. We suggest that an evaluation of steroid hormone receptors is justified before general hormonal or anti‐hormonal treatment of patients.