Roles of estrogen receptors alpha and beta in differentiation of mouse sexual behavior

Sex differences in brain and behavior are ubiquitous in sexually reproducing species. Developmental differences in circulating concentrations of gonadal steroids underlie many sexual dimorphisms. During the late embryonic and early perinatal periods, the testes produce androgens, thus, male brains are exposed to testosterone, and in situ testosterone is aromatized to estradiol. In contrast, females are not exposed to high concentrations of testosterone or estradiol until puberty. In many species, neural sex differences and sexually dimorphic behaviors in adults are initiated primarily by estradiol exposure during early development. In brain, estradiol activates two independent processes: masculinization of neural circuits and networks that are essential for expression of male-typical adult behaviors, and defeminization, the loss of the ability to display adult female-typical behaviors. Here, data for the roles of each of the known estrogen receptors (estrogen receptor alpha and estrogen receptor beta) in these two processes are reviewed. Based on work done primarily in knockout mouse models, separate roles for the two estrogen receptors are suggested. Estrogen receptor alpha is primarily involved in masculinization, while estrogen receptor beta has a major role in defeminization of sexual behaviors. In sum, estradiol can have selective effects on distinct behavioral processes via selective interactions with its two receptors, estrogen receptor alpha and estrogen receptor beta.     

Combined estrogen receptor alpha and estrogen receptor beta genotypes influence the age of menarche

BACKGROUND: Age at menarche has a strong genetic influence. We reported recently an association between the XbaI (351A-->C)and PvuII (397T-->C) polymorphisms of the estrogen receptor (ER)alpha gene with the age of menarche in Greek adolescents. In the present study, we examined whether ERbeta genotypes alone, or in combination with ERalpha genotypes, may also influence onset of menarche. METHODS: We performed genotyping for the single nucleotide polymorphisms 1730A-->G and 1082G-->A of the ERbeta gene and examined their association with the age of menarche in the same cohort of 145 Greek girls. We then looked for a possible effect of combined ERalpha and beta genotypes on the age of menarche. RESULTS: Menarche occurred 7 months later in girls with the AA genotype of the 1730A-->G polymorphism than in girls with the AG genotype (mean +/- SD: 13.23 +/- 1.24 versus 12.66 +/- 1.26 years, respectively; P = 0.005). The 1082G-->A polymorphism was not detected in any of the girls examined. A significant effect of combined ERalpha and beta genotypes was also apparent. Menarche occurred 11 months later in girls bearing the AA/TT,AA (ERalpha, ERbeta) genotypes compared with girls with the CC/CC,AG genotype (13.30 +/- 1.27 nersus 12.41 +/- 1.28 years; P = 0.042). The difference remained significant after adjusting for body mass index (P = 0.034). CONCLUSION: Combined ERalpha and ERbeta polymorphisms may influence the age of menarche.     

Immunohistochemical analysis of estrogen receptor alpha, estrogen receptor beta and progesterone receptor in normal human endometrium

The endometrium expresses estrogen (ER) and progesterone receptors (PR), which are involved in autocrine and paracrine regulation processes in response to estrogen and progesterone. The aim of the present study was to evaluate immunohistochemical distribution patterns of estrogen receptor alpha (ER alpha), estrogen receptor beta (ER beta) and PR in normal human endometrial tissue with the use of monoclonal antibodies. Human endometria were obtained from 17 premenopausal patients undergoing surgery for non-malignant diseases and were classified to be in proliferative, early secretory and late secretory phases by histological and anamnestical means. Distribution patterns of the steroid receptors were evaluated using the IRS-score and the Mann-Whitney rank-sum test was used to compare the means. Correlation was assessed with the Spearman factor and linear regression analysis. ER alpha and PR expression decreased significantly (p<0.05) in glandular epithelium from the proliferative to the late secretory phase. ER beta expression showed a similar significant decrease (p<0.05), although staining intensity was lower than that of ER alpha. A significant correlation between expression of all three steroid receptors was observed (p<0.001). Distribution patterns of ER alpha, ER beta and PR in normal human endometrium showed a cyclic variation during the menstrual cycle. A significant correlation between expression of ER alpha, ER beta and PR was also demonstrated using regression analysis, indicating dependence of expression of these three steroid receptors. The present study shows the presence of steroid receptors in human endometrial epithelium, indicating that these cells respond to estrogen and progesterone and thus playing a significant role in endometrial physiology.     

Immunohistochemical expression of estrogen receptors alpha and beta in lobular neoplasia

The designation lobular neoplasia (LN) of the breast includes atypical lobular hyperplasia and lobular carcinoma in situ. Estrogen receptors (ER) play a significant role in breast carcinogenesis. In the present study, ER-alpha and ER-beta status are evaluated in 30 breast tissue specimens from patients whose main lesion was LN. A standard immunohistochemical procedure, using monoclonal antibodies for ER-alpha and ER-beta, was applied to the lesion and the adjacent normal breast tissues, the latter serving as control. In all cases, both receptors were expressed in LN as well as in normal breast ducts and lobules. Concerning ER-alpha, the Allred score and the percentage of ER-alpha-positive cells were significantly higher in LN than in the adjacent normal breast tissue. On the contrary, regarding ER-beta, the Allred score and the percentage of ER-beta-positive cells were significantly lower in LN compared with normal adjacent breast tissue. Greater increase in the percentage of ER-alpha-positive cells was associated with a smaller reduction in the percentage of ER-beta-positive cells and vice versa (Spearman’s rho = −0.5044, p = 0.001). In conclusion, upregulation of ER-alpha and downregulation of ER-beta may represent two discrete molecular events in LN pathogenesis. Of notice, a mutually limiting interaction may exist between the two events.     

Estrogen receptors alpha and beta (ERalpha and ERbeta) and androgen receptor (AR) in human sperm: localization of ERbeta and AR in mitochondria of the midpiece

BACKGROUND: The central role of estrogens and androgens in the male reproductive system has focused attention on the presence and distribution of their cognate receptors [estrogen receptor (ER) alpha, ERbeta and androgen receptor (AR)] in male reproductive tissues and cells. Since the presence of steroid hormone receptors in mitochondria of mammalian cells has been well documented, we investigated the possibility of mitochondrial localization of sex steroid hormone receptors in sperm. METHODS AND RESULTS: Applying immunofluorescence labelling and confocal laser scanning microscopy we show that the estrogen receptor beta and the AR of human sperm are specifically enriched in the midpiece, at the site of the mitochondria, which were visualized by labelling with the vital dye CMX. Nuclear and mitochondrial localization of AR was also detected in LnCap human prostate cancer cells. Differentially, most of the ERalpha immunostaining is in the form of a compact zone at a region corresponding to the equatorial segment of the upper post-acrosomal region of the sperm head. Immunoblotting experiments using sperm extracts revealed the presence of a 66 and a 45 kDa protein reacting with the ERalpha antibody, one 64 kDa protein reacting with the ERbeta antibody and a 110 and a 90 kDa protein reacting with the antibody against AR. CONCLUSIONS: Our findings suggest that the differential localization of AR and ER isoforms in human sperm reveals distinct roles of these receptors in the physiology of sperm cells and, perhaps, also in the process of fertilization.     

Upregulation of cell surface estrogen receptor alpha is associated with the mitogen-activated protein kinase/extracellular signal-regulated kinase activity and promotes autophagy maturation

Recently, accumulating evidence has implicated the dysregulation of autophagy as underlying the pathophysiology of several neurodegenerative diseases. The human neuronal cell line SH-SY5Y was exposed to 1-Methyl-4-phenylpyridinium (MPP⁺). The mechanism is that the sustained activation of the MAPK/ERK pathway by MPP⁺ alters autophagy selectively at the maturation step, significant increasing in autophagy formation and delaying in autophagy degradation in SHSY5Y cells. In this study, we provided evidences that estrogen was capable of promoting SHSY5Y cells survival in MPP⁺-treated group. In particular, the up-regulation of mERα, but not mERβ, was associated with a rapid and transient activation of ERK phosphorylation compatible with promoting autophagy maturation. The up-regulation of mERα changed the sustained activation of ERK phosphorylation in MPP⁺-treated group into a temporary activation. Taken together, these findings strongly support that the expression of mERα promotes the maturation of autophagosomes into functional autolysosomes by regulating ERK, determining SHSY5Y cells survival.     

Functional characterization of somatic point mutations of the human estrogen receptor alpha (hERalpha) in adenomyosis uteri

Endometriosis and adenomyosis uteri are chronic, benign diseases caused by the presence of endometrial tissue in ectopic locations, e.g. peritoneal or deep inside the myometrial wall of the uterus and/or in the rectovaginal septum. Although adenomyosis might be considered as a special form of endometriosis, both conditions differ with respect to clinical symptoms and treatment. Induction of a hypo-estrogenic state alone or in combination with surgical removal of the extra-uterine lesion is mostly sufficient for treatment of peritoneal endometriosis. By contrast, adenomyosis uteri rarely responds to hormonal therapy and usually requires a hysterectomy for cure. Consequently, the role of steroid hormone receptors with respect to the aetiology of either condition is still a matter of discussion. Using PCR/single strand conformation polymorphism analysis, we identified somatic estrogen receptor (ER) alpha gene mutations in three out of 55 samples from adenomyosis uteri. Functional characterization revealed that two of the mutant ERalpha proteins display severely impaired DNA-binding and transactivation properties secondary to an altered response to estrogens or changes in epidermal growth factor-mediated ligand-independent activation. Although the exact mechanism remains unknown, we suggest that mutation-related silencing of estrogen responsiveness might render endometriotic cells resistant to hypo-estrogenic conditions thereby accounting for failure of estrogen-ablative therapy in adenomyosis.     

Astrocyte-derived estrogen enhances synapse formation and synaptic transmission between cultured neonatal rat cortical neurons

Recent in vitro studies have found that astrocytes exert powerful control over the number of neuronal synapses, leading us to consider why glia can exert this control and what the underlying mechanism(s) may be. To understand the potential possibility, we studied the formation of synapses and synaptic function in primary rat cortical neurons. We found that primary cultured neonatal rat cortical astrocytes modulate synaptogenesis and synaptic function through producing and secreting estradiol into culture medium. The concentration of estradiol produced by pure cultured astrocytes increased in correspondence with the days of culture and the number of proliferating astrocytes, which peaked at 266+/-22 ng/l around day 14 of culture. When astrocyte-conditioned medium (ACM) was added into pure cultured cortical neurons, the number of synapses formed between cortical neurons increased by nearly sixfold. The mean frequency and the amplitude of mini-postsynaptic currents (mPSCs) increased from 13+/-4 events/min and 20.5+/-2 pA to 73+/-16 events/min and 29.1+/-3 pA, respectively. In the meantime, the level of estrogen receptor-alpha (ER-alpha) expressed on neonatal rat cortical neurons was significantly up-regulated. Moreover, the effect of ACM on synaptic formation and transmission was blocked by tamoxifen (estrogen receptor antagonist) in culture. After the treatment of tamoxifen, the number of synapses on neurons decreased from 79+/-9 to 32+/-3. The mean amplitude and frequency of mPSCs were also dropped to 24.5+/-2 pA and 35+/-10/min, respectively. Unexpectedly, exogenic estradiol can mimic the effect of ACM on synaptic formation and transmission. Finally, to understand whether astrocyte-derived estradiol regulates the synaptic transmission via presynapse, the release of presynaptic vesicle from neuron was monitored by FM 4-64 assay. The results showed that when ACM or exogenic estradiol was added into neurons, the kinetics of vesicle release speed are similar to that of neuronal cultured with astrocytes, which were faster than that of just pure neuronal cultures. These observations suggest that estrogen synthesized and secreted by astrocytes can regulate synapse formation and synaptic transmission.     

雌激素及雌激素受体α减轻谷氨酸对神经细胞的损伤

 目的：建立谷氨酸诱导的神经细胞损伤模型,观察雌激素及雌激素受体α（estrogen receptor α, ERα）对谷氨酸诱导的神经细胞损伤的作用。方法：原代培养小鼠大脑皮层神经细胞,神经元特异性烯醇化酶（neuron-specific enolase, NSE）免疫组化染色鉴定神经元的纯度。建立谷氨酸诱导的神经细胞损伤模型。用前期实验中已构建成功的ERα重组慢病毒（V-ERα-RFP-flag）感染经谷氨酸诱导的神经细胞。实时荧光定量PCR和Western blotting检测ERα mRNA和蛋白表达水平。实验分为3组：（1）对照组：用空慢病毒（V-RFP-flag）感染经谷氨酸诱导的神经细胞;（2）雌激素组：用雌激素干预经谷氨酸诱导的神经细胞;（3）慢病毒组：用V-ERα-RFP-flag感染经谷氨酸诱导的神经细胞。流式细胞术检测各组神经细胞凋亡率;实时荧光定量PCR及免疫荧光染色检测各组神经细胞中N-甲基-D-天冬氨酸受体1（N-methyl-D-aspartate receptor 1, NMDAR1）及囊泡膜谷氨酸转运体蛋白1（vesicular glutamate transporter protein 1, VGLUT1）的变化。结果：成功原代培养神经细胞,经NSE免疫组化方法鉴定神经元纯度大于90%。成功建立经谷氨酸诱导的神经细胞损伤模型。MOI=7的V-ERα-RFP-flag感染神经细胞72 h后,在荧光显微镜观察下可见到红色荧光表达,与对照病毒相比,能增加神经细胞中ERα mRNA和蛋白表达水平（P<0.01）。与对照组相比,雌激素组和慢病毒组细胞凋亡率降低（P<0.05）,且实时荧光定量PCR结果显示,雌激素组和慢病毒组的NMDAR1和VGLUT1 mRNA表达降低（P<0.05）,免疫荧光实验结果提示NMDAR1和VGLUT1阳性的细胞数减少（P<0.01）。结论：雌激素和ERα能减轻谷氨酸对神经细胞的损伤效应,该保护作用可能通过抑制NMDAR1和VGLUT1的表达来实现。     

Association of the estrogen receptor alpha gene polymorphisms with osteoporosis in the Mexican population

The estrogen receptor gene (ER alpha) has been implicated in the development of osteoporosis. In this study, the association of two ER alpha gene polymorphic markers (a TA dinucleotide repeat and a single nucleotide polymorphism, G2014A) with osteoporosis was tested in 70 osteoporotic women, 70 non-osteoporotic women and 500 subjects from the Mexican population. According to the genetic analysis of the Mexican population using eight unlinked polymorphic markers, we found that our population is structured into three subpopulations; therefore, the allele-phenotype relationship was analyzed with a statistical method that considered population stratification. We found that the G2014A polymorphism is associated with the presence of osteoporosis while the TA dinucleotide repeat is not. The G allele and the GG genotype frequencies of the G2014A marker were significantly higher in osteoporotic than in non-osteoporotic women. Likewise, subjects bearing the G allele in heterozygous or homozygous displayed lower values for lumbar bone mineral density and T score than those who did not present any G allele. The effect of confounders for osteoporosis on the association of G allele-osteoporosis was ruled out. In summary, we conclude that the G2014 polymorphism may become a useful marker for genetic studies of osteoporosis in the Mexican population.     

雌激素受体不同亚型在卵巢子宫内膜异位症在位内膜与异位内膜中的表达及其意义

目的 研究雌激素受体(ER)不同亚型在子宫内膜异位症的在位和异位内膜中的表达,以寻找其在不同病灶中的分布规律,探讨子宫内膜异位症的发病机制.方法 收集解放军总医院2004年1月-2006年12月行手术治疗的卵巢子宫内膜异位症石蜡标本,包括卵巢子宫内膜异位囊肿60例及其在位内膜60例(增生期各30例、分泌期各30例)以及正常子宫内膜30例(增生期和分泌期各15例).采用免疫组织化学(EnVision)方法检测上述组织中ERα和ERβ的表达.染色结果半定量化,并分析比较各种组织间的表达差异.结果 各组中,ERα和ERβ在腺上皮的表达与它们在间质细胞中的表达呈正相关.ERα蛋白在不同部位的表达:在位内膜ERα的表达(腺上皮和间质细胞阳性率分别为73.3%和76.7%)高于卵巢子宫内膜异位囊肿(腺上皮和问质细胞阳性率分别为43.4%和46.7%)和正常内膜的表达(腺上皮和间质细胞阳性率分别为56.7%和50.0%),均P<0.05.ERβ蛋白在不同部位的表达:卵巢子宫内膜异位囊肿(腺上皮和间质细胞阳性率分别为90.0%和76.7%)高于在位子宫内膜的表达(腺上皮和间质细胞阳性率分别为68.0%和63.3%),后者又高于正常子宫内膜(腺上皮和间质细胞阳性率分别为36.7%和26.7%),P均<0.05.在位内膜的ERα和ERβ蛋白表达在增殖期均高于分泌期,P均<0.05;异位内膜增殖期和分泌期的表达差异无统计学意义.ERα和ERβ蛋白在不同部位表达的比较:在正常内膜中ERα的表达略高于ERβ,但差异无统计学意义,P>0.05;卵巢子宫内膜异位囊肿中ERβ的表达高于ERα,P<0.05;而在位内膜中两种亚型表达差异无统计学意义.结论 子宫内膜异位症患者在位子宫内膜及异位内膜均有ERα和ERβ的表达,但与正常子宫内膜相比,在卵巢子宫内膜异位囊肿中ERβ表达占优势,而ERα表达受限.ERα和ERβ在不同组织中的分布及表达水平与子宫内膜异位症的发生和发展有着密切关系.     

Membrane estrogen receptor alpha is an important modulator of bone marrow C-Kit+ cells mediated cardiac repair after myocardial infarction

It has been validated that c-kit positive (c-kit⁺) cells in infarcted myocardium are from bone marrow (BM). Given the recent study that in the heart, estrogen receptor alpha (ERα) is involved in adaptive mechanisms by supporting cardiomyocytes survival via post-infarct cardiac c-kit⁺ cells, we tested a novel hypothesis that membrane ERα (mERа) supports survival of BM c-kit⁺ cells and enhance protective paracrine function for cardiac repair. Our data showed that myocardial infarction (MI) leads to an increase in c-kit⁺ first in bone marrow and then specifically within the infarcted myocardium. Also up-regulated mERа in post-infarct BM c-kit⁺ cells was found in day 3 post MI. In vitro co-culture system, mERа⁺ enhances the beneficial effects of BM c-kit⁺ cells by increasing their viability and reducing apoptosis. Post-infarct c-kit⁺ mERа⁺ cells population expresses predominant ERα and holds self-renewal as well as cardiac differentiation potentials after MI. In vivo, BM c-kit⁺ cells reduced infarct size, fibrosis and improved cardiac function. In conclusion, BM c-kit⁺ mERа⁺ exerted significantly cardiac protection after MI. A potential important implication of this study is that the manipulation of BM c-kit⁺ stem cells with ERа-dependent fashion may be helpful in recovering functional performance after cardiac tissue injury.     

Membrane estrogen receptors activate the metabotropic glutamate receptors mGluR5 and mGluR3 to bidirectionally regulate CREB phosphorylation in female rat striatal neurons

Along with its ability to directly regulate gene expression, estradiol influences cell signaling and brain functions via rapid, membrane-initiated events. In the female rat striatum, estradiol activates membrane-localized estrogen receptors to influence synaptic neurotransmission, calcium channel activity, and behaviors related to motor control. Yet, the mechanism by which estradiol acts to rapidly affect striatal physiology has remained elusive. Here we find that membrane estrogen receptors (ERs) couple to the metabotropic glutamate receptors mGluR5 and mGluR3, providing the framework to understand how membrane estrogen receptors affect striatal function. Using CREB phosphorylation as a downstream measure of ER/mGluR activation, membrane-localized estrogen receptor α (ERα) activates mGluR5 signaling to mediate mitogen-activated protein kinase (MAPK)-dependent CREB phosphorylation. Further, ERα and estrogen receptor β (ERβ) activate mGluR3 to attenuate L-type calcium channel-dependent CREB signaling. Interestingly, while this fundamental mechanism of ER/mGluR signaling was initially characterized in hippocampal neurons, estrogen receptors in striatal neurons are paired with a different set of mGluRs, resulting in the potential to functionally isolate membrane-initiated estrogen signaling across brain regions via use of specific mGluR modulators. These results provide both a mechanism for the rapid actions of estrogens within the female striatum, as well as demonstrate that estrogen receptors can interact with a more diverse set of surface membrane receptors than previously recognized.     

Association of repeat polymorphisms in the estrogen receptors alpha, beta, and androgen receptor genes with knee osteoarthritis

Genetic factors have been shown to play an important role in the etiology of osteoarthritis (OA). To elucidate the possible role of genetic variation in the estrogen receptors alpha and beta (ER-alpha, ER-beta) and androgen receptor (AR) genes with knee OA, the -1174(TA)(n), c.1092+3607(CA)(n), and c.172(CAG)(n) repeat polymorphisms of ER-alpha, ER-beta, and AR genes were studied. A case-control cohort of 158 patients with idiopathic knee OA and 193 controls were used. A significant difference was observed in the frequency distribution of -1174(TA)(9-25) and c.1092+3607(CA)(13-27) repeat polymorphisms of the ER-alpha and ER-beta genes between OA patients and controls (p<0.005 and p<0.0001, respectively). A significantly increased odds ratio (OR) for knee OA was observed in individuals having long alleles (LL) genotype for ER-alpha gene and LL and one short and one long allele (SL) genotypes for ER-beta gene compared to individuals with the short alleles (SS) genotype (95% CI 1.03-3.5; p=0.04 and CI 2.4-8.3 and 2.5-7.5; p < 0.001, respectively). When ORs were adjusted for various risk factors, it was observed that women with LL genotypes for ER-beta and AR genes showed significantly increased risk for OA development (p=0.002 and 0.001). An association between c.1092+3607(CA)(13-27) and c.172(CAG)(8-34) repeat polymorphisms of the ER-beta and AR genes and knee OA was found in individuals of Greek descent.     

Expression of estrogen and progesterone receptors in cytologic specimens using various fixatives

Estrogen and progesterone receptor reactivity may be useful in identifying possible primary sites of metastatic disease or directing therapy in tumors of the female genital tract, including breast, ovary, and endometrium. Various methods have been described for the immunocytochemical evaluation of estrogen receptor (ER) and progesterone receptor (PR) status of cytologic specimens but our results have been variable. We evaluated the effectiveness of various fixatives [cytospin collection fluid, Shandon, Pittsburgh, PA (SH); ethanol (ETH); and formalin (FOR)] for fixation of smears (SM) and cell block (CB) material. The percentage and intensity of tumor nuclei of SM, CB, and tissue sections (TS) stained for ER and PR by the avidin-biotin-peroxidase complex technique were compared. Samples were considered ER or PR positive when ≥20% of tumor nuclei were stained. The sensitivity of ER analysis of SMs and CBs in each fixative compared to formalin-fixed paraffin-embedded tissue sections were as follows, SM (SH) 88%, SM (ETH) 14%, CB (SH) 58%, CB (ETH) 43%, and CB (FOR) 70%. The sensitivity of PR determination on SMs and CBs was SM (SH) 71%, SM (ETH) 6.0%, CB (SH) 25%, CB (ETH) 33%, CB (FOR) 80%. These findings indicate that of the fixatives evaluated for ER analysis SMs fixed in SH provided the best results. For PR evaluation, CBs fixed in FOR gave the best results. Diagn Cytopathol 1996;15:78–83. © 1996 Wiley-Liss, Inc.     

左旋18-甲基炔诺酮对大鼠雌激素水平及下丘脑雌激素受体阳性细胞的影响

目的:观察左旋18-甲基炔诺酮(LNG)对大鼠雌激素(E)水平及下丘脑内雌激素受体(ER)阳性细胞的影响。方法:正常雌性SD大鼠分为给药对照组、给药组、停药对照组、停药组,应用免疫组织化学方法显示下丘脑ER阳性细胞并检测血清E浓度。结果:给药组较给药对照组E浓度下降,弓状核(Arc)、下丘脑腹内侧核(VMH)内ER阳性细胞的数量减少、光密度下降。停药后基本恢复正常。结论:长期LNG作用导致给药大鼠血清E水平下降;长期LNG作用引起大鼠下丘脑ER数量减少、活性减低,推测ER可能参与影响促性腺激素释放激素的分泌;停药后ER的形态学变化恢复正常,所以LNG的作用基本上是可逆的。     

Expression of pepsinogen II with androgen and estrogen receptors in human prostate carcinoma

The expression of pepsinogen II (PG II), an aspartyl proteinase usually involved in the digestion of proteins in the stomach, was immunohistochemically investigated in conjunction with androgen (AR) and estrogen receptor (ER) status in prostate adenocarcinomas. Of a total of 38 samples obtained from radical prostatectomies, 23 tumors (60.5%) were positive for PG II and there was a significant positive correlation to the expression of AR but not to ER. Cells positive for PG II were localized mainly to the peripheral zones of tumorous glands which, in normal prostate, are negative, and in areas also expressing AR. In addition, a significant correlation between AR and ER was detected in the prostate carcinomas examined, which suggests a hormone-dependent status. On the basis of these results, PG II expression might be closely related to hormonal alterations associated with the development of prostate tumors.